Health and Social Development, Faculty of (Okanagan)
Health and Exercise Sciences, School of (Okanagan)
DSpace
UBCO
Palmer, Kierstyn Lainey
Master of Science - MSc
University of British Columbia
Purpose: People with spinal cord injuries (SCI) represent a population with high prevalence of chronic pain. Neuropathic pain and musculoskeletal pain are two types of pain that affect this population and have varying symptomology. Despite high prevalence of pain and the need for safe, specific, and effective treatment options, research on biopsychosocial differences between chronic pain types in SCI is limited. The purpose of this study was to compare pain intensity and interference, subjective well-being, and physical activity between those with SCI and chronic neuropathic pain versus those with SCI and chronic musculoskeletal pain. Understanding differences between pain types will provide valuable insight for future research and treatment of SCI chronic pain. Methods: This study was a cross-sectional study assessing pain severity, pain interference, positive affect, negative affect (i.e., stress), life satisfaction, and leisure time physical activity in 46 individuals with chronic pain and SCI. This study used natural groups, where individuals were categorized as “NP group” or “MSK group” based on their primary (worst) pain problem reported on pain questionnaires. Means for each group were compared using analysis of variance (ANOVA), analysis of covariance (ANCOVA) tests, and effect size calculations. Results: Those in the NP group had significantly greater pain severity than those in the MSK group (p=0.026). There were no other significant differences found between groups. However, effect size calculations indicated meaningful differences between groups, including greater pain interference (small to medium effect), more stress (medium effect), and lower satisfaction with life (small to medium effect), in those with NP than those with MSK. And yet, participants with NP also had greater positive affect (small effect) and more minutes of physical activity per week (small to medium effect) than those with MSK. Conclusion: The results suggest significant differences in pain, as well as meaningful differences in well-being and leisure time physical activity between those with SCI and chronic NP versus chronic MSK. Further research is needed to look into mechanisms that might account for these differences. Clinical interventions should focus on multiple components of the biopsychosocial model to improve the lives of people with SCI and chronic pain. Lastly, emphasis should be made on providing more support to those with chronic NP as they appear to experience worse outcomes of pain, stress, and life satisfaction.
PAIN, WELL-BEING, AND PHYSICAL ACTIVITY IN ADULTS WITH CHRONIC PAIN AND SPINAL CORD INJURY by Kierstyn Lainey Palmer B.Sc., Acadia University, 2022 A THESIS SUBMITTED IN PARTIAL FUFILLMENT OF THE REQUIREMENTS FOR THE DEGREE OF MASTER OF SCIENCE in THE COLLEGE OF GRADUATE STUDIES (Health and Exercise Sciences) UNIVERSITY OF BRITISH COLUMBIA (Okanagan) November 2024 © Kierstyn Lainey Palmer, 2024 ii The following individuals certify that they have read, and recommend to the College of Graduate Studies for acceptance, the thesis entitled: PAIN, WELL-BEING, AND PHYSICAL ACTIVITY IN ADULTS WITH CHRONIC PAIN AND SPINAL CORD INJURY submitted by Kierstyn Lainey Palmer in partial fulfilment of the requirements for the degree of Master of Science Examining Committee: Dr. Kathleen Martin Ginis, Faculty of Health and Social Development. Supervisor Dr. Chris West, Faculty of Medicine. Supervisory Committee Member Dr. Femke Hoekstra, Faculty of Medicine. Supervisory Committee Member Dr. Jasmin Ma, University of British Columbia (Vancouver). University Examiner iii Abstract Purpose: People with spinal cord injuries (SCI) represent a population with high prevalence of chronic pain. Neuropathic pain and musculoskeletal pain are two types of pain that affect this population and have varying symptomology. Despite high prevalence of pain and the need for safe, specific, and effective treatment options, research on biopsychosocial differences between chronic pain types in SCI is limited. The purpose of this study was to compare pain intensity and interference, subjective well-being, and physical activity between those with SCI and chronic neuropathic pain versus those with SCI and chronic musculoskeletal pain. Understanding differences between pain types will provide valuable insight for future research and treatment of SCI chronic pain. Methods: This study was a cross-sectional study assessing pain severity, pain interference, positive affect, negative affect (i.e., stress), life satisfaction, and leisure time physical activity in 46 individuals with chronic pain and SCI. This study used natural groups, where individuals were categorized as “NP group” or “MSK group” based on their primary (worst) pain problem reported on pain questionnaires. Means for each group were compared using analysis of variance (ANOVA), analysis of covariance (ANCOVA) tests, and effect size calculations. Results: Those in the NP group had significantly greater pain severity than those in the MSK group (p=0.026). There were no other significant differences found between groups. However, effect size calculations indicated meaningful differences between groups, including greater pain interference (small to medium effect), more stress (medium effect), and lower satisfaction with life (small to medium effect), in those with NP than those with MSK. And yet, participants with NP also had greater positive affect (small effect) and more minutes of physical activity per week (small to medium effect) than those with MSK. iv Conclusion: The results suggest significant differences in pain, as well as meaningful differences in well-being and leisure time physical activity between those with SCI and chronic NP versus chronic MSK. Further research is needed to look into mechanisms that might account for these differences. Clinical interventions should focus on multiple components of the biopsychosocial model to improve the lives of people with SCI and chronic pain. Lastly, emphasis should be made on providing more support to those with chronic NP as they appear to experience worse outcomes of pain, stress, and life satisfaction. v Lay Summary People with spinal cord injury (SCI) often experience pain, including neuropathic (nerve) pain and musculoskeletal (muscle) pain. Learning about differences between the experiences of those with varying pain types may help develop treatments that are more specific to their individual pain problems. Biological, psychological, and social factors are known to impact pain. As such, this thesis project aimed to see if there were differences in pain, well-being, and physical activity in those with SCI and different types of chronic pain. We found that those with neuropathic pain may experience more pain, stress, and lower life satisfaction than those with musculoskeletal pain. Despite this, people with neuropathic pain tend to have more positive affect and do more physical activity. Our results suggest there are meaningful differences in pain, well-being, and physical activity between chronic pain types that should be considered in future research and treatment. vi Preface This thesis is based on work conducted at University of British Columbia (Okanagan) by Kierstyn Palmer and Dr. Kathleen Martin Ginis. This study uses a subset of the baseline data collected from the larger EPIC-SCI trial, based in Kelowna and Vancouver BC. Dr. Kathleen Martin Ginis was responsible for obtaining funding, selecting measures, authoring the ethics application that was submitted to the Behavioural Research Ethics Board at University of British Columbia (Okanagan), as well as the design and implementation of the primary EPIC-trial. For the current cross-sectional study, Kierstyn Palmer was responsible for formulating the research question, collecting pain measures (including pain interviews) from a subset of participants, and selecting variables from the EPIC-SCI dataset for inclusion in this study. Furthermore, Kierstyn was responsible for coding participants’ pain phenotypes, along with data analysis and interpretation. Dr. Kathleen Martin Ginis provided Kierstyn with assistance with study design, variable selection, data analysis, and interpretation of findings. Generative AI was not used for any aspect of this work. This research study has not yet been published. This research study was approved by the Clinical Research Ethics Board at the University of British Columbia. #H19-01650. A pragmatic randomized controlled trial testing the effects of the international scientific SCI exercise guidelines on SCI chronic pain: protocol for the EPIC-SCI trial vii Table of Contents Abstract…………………………………………………………………………………...….....…iii Lay Summary …………………………………………………………………………......…....…v Preface………………………………………………………………...……………...……………vi Table of Contents…………………………………………………………………… …...…...…vii List of Tables………………………………………………………………………. ………......…x List of Figures…………………………………………………………………… …………....…xi Acknowledgements …………………………………………………………………. …….....…xii Statement of Positionality…..…………………………………………………………. ..……..xiii Chapter 1: Introduction.…………………………………….…………………………… ………1 1.1 Rationale..........................................................................................................................1 1.2 Spinal Cord Injury...........................................................................................................3 1.3 Pain and Spinal Cord Injury............................................................................................4 1.4 Biopsychosocial Model and Chronic Pain.......................................................................7 1.5 Pain and Subjective Well-Being in Spinal Cord Injury ...................................................8 1.6 Benefits of Physical Activity..........................................................................................13 1.7 Purpose ..........................................................................................................................16 Chapter 2: Hypotheses...………………….……………………………………………..………..17 2.1 Primary Hypothesis: Levels of Pain...............................................................................17 2.2 Secondary Hypothesis: Levels of Subjective Well-Being..............................................17 2.3 Tertiary Hypothesis: Levels of Physical Activity…..………….....................................17 Chapter 3: Methodology...………………….………………………………………………..……18 3.1 Study Design ..................................................................................................................18 3.2 Participants ...................................................... ..............................................................19 3.3 Inclusion and Exclusion Criteria.....................................................................................20 viii 3.4 Study Protocol......................................................................................................................20 Chapter 4: Data Analysis…….………………………………..…………………….……….…….…26 4.1 Pain Classification................................................................................................................26 4.2 Data Analysis and Protocol for Missing Data......................................................................26 Chapter 5: Results.…………………………………………………….…………….……………......28 5. 1 Participant Demographic Characteristics ……………………………………………..…30 5.2 Preliminary Analyses……………………………………….…………………………...…31 5.3 Hypothesis Tests…………………………………………………………………..….....…33 5. 4 Results Summary…………………………………………………….……………....……37 Chapter 6: Discussion.…………………………………………………….…………………….….…38 6.1 Providing Context and Meaning to Statistical Results…………………………..…………………39 6.2 Pain severity and interference…………………………..…………………………………..………40 6.2.1 Biological mechanisms affecting pain severity………………………………….………41 6.2.2 Psychological mechanisms affecting pain severity..…………………………….………44 6.2.3 Social mechanisms affecting pain severity…...…………………………………….……46 6.2.4 Mechanisms affecting pain interference……..……………………………………..……47 6.3 Subjective well-being…………………………………….…………………………………………49 6.3.1 Life Satisfaction………………………………………………………………………….49 6.3.2 Negative Affect ………………………………………….………………………………50 6.3.3 Positive Affect ……………………………………..……………………………………50 6.3.4 Positive Affect as a Coping Mechanism for those with SCI and NP……………………52 6.4 Leisure Time Physical Activity………………………….……………………………………….…55 6.5 Strengths and Limitations ……………………………….………………………………..….......…58 Chapter 7: Conclusions …………………………….……………………………………………….…62 7.1 Contributions, Implications, and Future Directions…………………………….…………….......…62 7.2 Conclusion…………………………………………………………………..….……………………63 ix References ……………….………….………………………………..……………………………...….64 Appendices……………….………….………………………………..…………………………...…….85 Appendix A: Study Materials …….………….……………………………………….…………85 Appendix B: Data Transformations…..….……………….………………………………..…….99 x List of Tables Table 1: Outcome measurements………………………………………………………………..…..……19 Table 2: Participant Demographic Characteristics …………………………………………..…...…..…..29 Table 3: Tests for assumptions of ANOVA………………………………………........................…...….32 Table 4: Means, Standard deviations, ANOVA and Effect Size Results…..……………..………………35 Table 5: Means, Standard deviations, ANCOVA and Effect Size Results ………...……………….……35 Table 6: Summary of Results including all variables and hypotheses ………………………...…..…..…36 xi List of Figures Figure 1: Flow of Participants Through Study …………………………………………………………28 xii Acknowledgments If there was one thing that led me to doing my master’s at UBCO, it would be open-mindedness. I never envisioned I would do a master’s degree and I had never heard of Kelowna, BC, until the year I moved here. Am I ever glad I did. Writing this thesis was the most challenging thing I have ever attempted, but also the most rewarding. Now that it is behind me, I gained confidence that I can do anything I set my mind to- with the support and encouragement from the right people. I owe this accomplishment to many individuals, but firstly, my supervisor Dr. Kathleen Martin Ginis. I saw something in Kathleen that made me want to move across the country, and she saw something in me that made her want the same. I am eternally grateful for the opportunity she has given me to expand my horizons in pain research. Because of her, I have felt passionate, energized, and excited about having a place in research. Along with that, I have found a home and second family in the most special place. To Kathleen, you are superwoman to me. Over the course of the last two years, I have been amazed and in awe of your ability to juggle your many hats. To this day I am astonished with how you always manage to carry yourself with so much grace through it all. Being in your presence and having you believe in me has been inspiring and allowed me to reach new levels. I would like to acknowledge my thesis advisory committee members, Dr. Chris West and Dr. Femke Hoekstra. I am extremely appreciative to have had the perspectives of such knowledgeable researchers on this project. Your expertise in your respective areas of research has added critical insight to this project that I am grateful for. I look forward to bringing the knowledge you have taught me into my career and continuing to learn from the work that you do for those with spinal cord injury. xiii I would like to extend a warm thank you to my lab mates who welcomed me and supported me along the way: Kenedy Olsen, for being my first friend at UBCO and continuing to support my journey long after you left our lab; Rob Buren, for sharing your passion for pain research and never turning down an invitation to help me make sense of my own thoughts; Matteo Ponzano, for offering me new opportunities and teaching me new skills; Aleks Jevdjevic, for always being up for a coffee walk or to lend supportive advice; Haley Berrisford, for the endless support and encouragement; and finally Nate, for being our go to for all things (but especially physiology, PowerPoint, and baseball). To you all- I am grateful for your friendship and for welcoming me into the lab with open arms. Thank you. I would like to acknowledge my undergraduate supervisor, Dr. Nick Bray, who took a chance on me that would change my life. Nick, without your openness to take me on with zero research experience and patience teaching me how to first-author a systematic review, I would not have had the ability to be here doing this work. I am forever grateful for all that you have taught me and the support you have given me not only in undergrad, but during the duration of this MSc. Among many things, you taught me to celebrate all the wins (even the small ones) more than you dwell on the losses. Your advice is something I have leaned on to get this done. Lastly, to my family for supporting my dreams. To my mom, thank you for instilling in me curiosity, confidence, and appreciation for the art of reading and writing. To my sister, Ashtyn, thank you for being a role model to me; your hard work and dedication is something I look up to. To my dad, thank you for believing in me every day. It is you who has never failed to get me through the days I don’t believe in myself. xiv Statement of Positionality I (Kierstyn Palmer) am from a rural community in Prince Edward Island, Canada, where I attended public school in French Immersion and played varsity athletics. I am a second-generation university graduate, however the only child of my siblings to pursue secondary education. My baccalaureate degree was graciously supported by the Harrison McCain Scholarship and Acadia Excellence Scholarships in Wolfville, Nova Scotia, Canada. I identify as a cis-gendered female and previously suffered from a chronic back injury in high school. I have no personal connection with spinal cord injury but, as a result of my back injury, I have personal experience with chronic pain, which sparked my interest in pain research. As a result, I worked on an unfunded project during the summer after completion of my bachelor’s degree to publish a systematic review as lead author focusing on exercise, brain function, and pain in adults with chronic pain. My personal experience with chronic pain is an advantage as the primary investigator as this perspective allows me to navigate with empathy and understanding as I feel that I can relate to those with chronic pain. I recognize that with this advantage comes potential for my experience to introduce bias during analysis and interpretation of results. To mitigate these biases, analysis and interpretation was done with guidance from Dr. Kathleen Martin Ginis. My research is currently supported by the UBCO Graduate Studies Research Scholarship under supervision of Dr. Kathleen Martin Ginis and guidance of lab mates in the SCI Action Canada Lab. I feel grateful to have space to learn and create at the University of British Columbia Okanagan, where my research is inspired by personal experience and the desire to improve the lives of others experiencing chronic pain. 1 Chapter 1. Introduction 1.1 Thesis Rationale Pain and pain-related diseases are the leading cause of disability worldwide (Vos et al., 2015). Approximately 20% of the population suffer from chronic pain; in Canada, this is an estimated 8 million people (Government of Canada, 2023). To be classified as having chronic pain, individuals must experience pain for three months or more (Treede et al., 2015). Those who experience pain for such lengths of time often demonstrate continued nervous system dysfunction accompanying pain that significantly interferes with their daily activities and reduces quality of life (Fine, 2011; Yang & Chang, 2019). Yearly, millions of dollars are allocated to pain-related treatments, which have historically consisted of ineffective and addictive medications (Chou et al., 2020; Vargas et al., 2018). People with spinal cord injuries (SCI) represent a population with a high prevalence of chronic pain. Although an estimated 68% of people with SCI report experiencing chronic pain (Hunt et al., 2021), pain research on people with SCI is limited. Notably, people with SCI report their pain being more debilitating than the injury itself (Anson & Shepherd, 1996). Despite this astounding reality, the most commonly prescribed treatments for pain for people with SCI are still pharmaceutical treatments, which have only shown up to 50% effectiveness in 30% of patients (Siddall & Middleton, 2015), speaking to the need for alternative treatments for SCI-related pain. The most common types of chronic pain reported in individuals with SCI are chronic neuropathic pain (NP) and chronic musculoskeletal (MSK) pain (Hunt et al., 2021). These pain types differ widely in their symptomology. MSK pain symptoms encompass throbbing, dull, aching feelings of pain which are often localized to a specific area. NP symptoms are typically 2 described as burning, shock-like, and tingling feelings of pain which is often non-localized (El-Tallawy et al, 2021; Zalh et al, 2023). Despite their different symptomology, both types of pain affect individuals’ physical, cognitive, and emotional functioning and impact quality of life (Dogru Huzmeli & Melek, 2017; Zahl et al., 2023). There has been a recent shift to seeking holistic, multi-dimensional treatment recommendations for pain as more findings point to pain being a subjective experience, affected by not only biological but psychological and social factors. There is accumulating evidence to suggest that physical activity promotes positive changes in physiological measures, such as fitness and cardiometabolic health in people with SCI (Van Der Scheer et al., 2017). In addition, a recent meta-analysis reported positive effects of exercise on overall well-being, including subjective, psychological, and social well-being as well as health-related quality of life (Ponzano et al., 2024). Adding to this, another recent systematic review argues for the dual-benefitting effects of exercise interventions, reducing pain and altering brain function in pain-related areas in populations of people with chronic pain (Palmer et al, 2023). Furthermore, physical activity is considered in the CanPain SCI clinical practice guidelines recommendations for neuropathic pain management after SCI (Loh et al., 2022). Taken together, whilst considering a biopsychosocial approach to chronic pain management, this evidence suggests that physical activity may have the potential to improve pain through all three physical, cognitive, and social aspects. However, there is little data comparing, pain, well-being, and physical activity across different SCI-related pain problems (NP and MSK). Therefore, the proposed project is a cross-sectional study to compare levels of pain, well-being, and physical activity in people with chronic NP and/or MSK pain. This study addresses a critical knowledge gap in research of an understudied population and will therefore help inform 3 clinical recommendations and future practices for improving the quality of life of people with SCI experiencing chronic pain. 1.2 Spinal Cord Injury Spinal cord injury (SCI) is defined as any traumatic or non-traumatic event that causes damage to the spinal cord and results in a loss of motor, sensory or autonomic function (temporarily or permanently) (Maynard et al., 1997). Injury can be caused by an incision, compulsion, or contusion, commonly resulting from traffic accidents, gunshot and knife injuries, falls, and sports injuries (Nas, 2015). The effects of SCI on functionality are largely related to whether the injury is considered complete or incomplete (Nas, 2015). Complete SCIs are injuries that result in complete sensory and motor loss to regions distal to the injury level, while incomplete SCIs are injuries that result in partial loss of sensory and/or motor function below the injury level (Nas, 2015). The terms “tetraplegia” and “paraplegia” are commonly used when referring to an SCI as they provide descriptive information about functionality of individuals. Tetraplegia is used to describe a cervical SCI that impairs sensory and/or motor and/or autonomic function in the areas of the body under control of the cervical segments of the spinal cord that are affected, while paraplegia is used to describe thoracic, lumbar, or sacral SCI that impairs sensory and/or motor and/or autonomic function in the areas of the body under control of the sacral segments of the spinal cord that are affected (Nas, 2015). A simplistic distinction between the two is that arm function is affected during tetraplegia, but not paraplegia (Nas, 2015). Considering its key role in whole-body function, damage to the spinal cord can have detrimental and varying effects to those affected. It is estimated that 40-80 million people worldwide experience SCI, which is accompanied by disability, reduced quality of life, and 4 potentially debilitating, life threatening secondary complications including severe pain (Nas, 2015; World Health Organization, 2013). Although disability due to loss of motor function is commonly regarded as the most impairing complication after traumatic SCIs, Anson and Shepherd report a tragic reality for many people with SCI; their SCI-related pain is more debilitating than the injury itself (Anson & Shepherd, 1996). 1.3 Pain and Spinal Cord Injury Pain Definitions and Classifications Pain is defined as “an unpleasant sensory and emotional experience associated with actual or potential tissue damage” (Loeser & Treede, 2008). Historically, there has been a host of different pain classifications used across the field of SCI pain research (Bryce, Biering-Sørensen, Finnerup, Cardenas, Defrin, Ivan, et al., 2012). The International Spinal Cord Injury Pain (ISCIP) Classification was created to address the discrepancy in pain classifications by combining the three most commonly used classification systems (Bryce, Biering-Sørensen, Finnerup, Cardenas, Defrin, Ivan, et al., 2012). Therefore, the ISCIP is currently the most comprehensive system for classifying SCI pain. However, its authors still speak to the challenges and ambiguity faced when classifying pain subtypes (Bryce, Biering-Sørensen, Finnerup, Cardenas, Defrin, Ivan, et al., 2012). The ISCIP identifies four types of pain experienced by those with SCI; including nociceptive, neuropathic, other pain, and unknown pain (Bryce, Biering-Sørensen, Finnerup, Cardenas, Defrin, Lundeberg, et al., 2012). The authors identify subtypes of nociceptive pain and neuropathic pain based upon previous classifications; these subtypes include MSK, visceral, and other (nociceptive pain) and at-level, below-level, and other (neuropathic pain) (Bryce, Biering-Sørensen, Finnerup, Cardenas, Defrin, Lundeberg, et al., 2012). The hierarchical system 5 also includes a third tier with common primary sources and/or pathologies accompanying each subtype (Bryce, Biering-Sørensen, Finnerup, Cardenas, Defrin, Lundeberg, et al., 2012). Nociceptive Pain (Musculoskeletal) The International Association for the Study of Pain defines nociceptive pain as “pain arising from activation of nociceptors”, otherwise stated as pain arising from activation of “a sensory receptor that is capable of transducing and encoding noxious stimuli” (Loeser & Treede, 2008). Under this definition, to classify pain as nociceptive, it must be the result of nociception in an area where sensory receptors are free from damage that would inhibit them from transducing signals. One of its subtypes, MSK pain, is used to describe pain that falls into this category, but arises from nociceptors specifically belonging to a region of the MSK system, such as muscles, tendons, ligaments, joints, and bones (Bryce, Biering-Sørensen, Finnerup, Cardenas, Defrin, Lundeberg, et al., 2012). Importantly, this definition requires there to be sensory preservation in the region pain is believed to arise from (Bryce, Biering-Sørensen, Finnerup, Cardenas, Defrin, Lundeberg, et al., 2012). MSK pain encompasses pain stemming from MSK conditions inclusive of joint arthritis, spinal fractures, muscle injury, rotator cuff tendinopathy and muscle spasms (Bryce, Biering-Sørensen, Finnerup, Cardenas, Defrin, Lundeberg, et al., 2012). This is in contrast to another subtype of nociceptive pain, visceral pain, which arises from nociceptors in the visceral structures, which includes the thorax, abdomen, or pelvis, and is thought to be involved with pathology of internal factors like constipation, infections, and more (Bryce, Biering-Sørensen, Finnerup, Cardenas, Defrin, Lundeberg, et al., 2012). Other nociceptive pain encompasses pain that does not fit the previously described criteria for either MSK or visceral; for example, pain 6 from pressure sores, or headaches (Bryce, Biering-Sørensen, Finnerup, Cardenas, Defrin, Lundeberg, et al., 2012). Neuropathic Pain The second type of pain identified in the 2012 ISCIP classification is NP, which is defined as ‘‘pain caused by a lesion or disease of the somatosensory system’’ (Bryce, Biering-Sørensen, Finnerup, Cardenas, Defrin, Lundeberg, et al., 2012; T. S. Jensen et al., 2011). This type of pain is often spontaneous and presents as a variety of symptomology including burning, tingling, shocking, and shooting pains (Zahl et al., 2023). Under its current classification, NP is differentiated by several subtypes, including at-level, below-level, and other NP (Bryce, Biering-Sørensen, Finnerup, Cardenas, Defrin, Lundeberg, et al., 2012). At-level SCI encompasses pain that presents within three dermatomes below the individual’s level of injury and is thought to arise from nerve damage resulting from compression of the spinal cord, nerve roots, and/or cauda equina (Bryce, Biering-Sørensen, Finnerup, Cardenas, Defrin, Lundeberg, et al., 2012). Below-level SCI encompasses pain that presents in any of the dermatomes below the three dermatomes associated with individual’s level of injury and is thought to arise from spinal cord ischemia or spinal cord compression (Bryce, Biering-Sørensen, Finnerup, Cardenas, Defrin, Lundeberg, et al., 2012). The subtype of other NP encompasses pain that is thought to arise from carpal tunnel syndrome, trigeminal neuralgia, and diabetic pain (Bryce, Biering-Sørensen, Finnerup, Cardenas, Defrin, Lundeberg, et al., 2012). The “other” and “unknown” types of pain are used to classify pain resulting from conditions like fibromyalgia and Complex Regional Syndrome or of unknown origin, respectively (Bryce, Biering-Sørensen, Finnerup, Cardenas, Defrin, Lundeberg, et al., 2012). 7 Pain Prevalence in SCI Due to the many different definitions of pain types prior to the ISCIP classifications, it has been difficult to calculate the prevalence of SCI related pain, leading to large variations in estimates (Bryce, Biering-Sørensen, Finnerup, Cardenas, Defrin, Lundeberg, et al., 2012). This is important when considering the reported prevalence of all pain following SCI is estimated to be between 25-96% (Bryce, Biering-Sørensen, Finnerup, Cardenas, Defrin, Lundeberg, et al., 2012; Dijkers et al., 2009; Siddall et al., 2003). A systematic review and meta-analysis was conducted in 2021 on 37 studies to compare rates of SCI-related pain after SCI. This was the first review conducted using the comprehensive ISCIP pain classification system (Hunt et al., 2021). According to this review, 68% of people develop some type of chronic pain following a SCI (Hunt et al., 2021). The two most prevalent types of chronic pain reported in the reviewed studies were NP and MSK pain, affecting 58% and 56% of people with SCI, respectively (Hunt et al., 2021). These numbers are consistent with previous literature suggesting that the prevalence of chronic pain after SCI averages around 65% across multiple studies (Finnerup, 2013; Siddall & Loeser, 2001). As chronic MSK pain and chronic NP are the most prevalent types of chronic pain following SCI, they will be the focus of this study. 1.4 The Biopsychosocial Model of Health and its Application to Chronic Pain The Biopsychosocial Model was first used to hypothesize about the integration of the mind and body in 1977 by Gregor Engel (Gogineni et al., 2023; Trachsel et al., 2024). He provided in depth description into its implication for health and disease; which included describing complex interactions between biological, psychological, and social factors that affect an individual’s health (Gogineni et al., 2023; Trachsel et al., 2024). For example, taking into 8 account both environmental and genetic interactions that affect development of mood related disorders (Craig, 2023). A number of theories have been developed to attempt to understand pain pathology. For example, the gate-control theory was proposed in 1965 and was particularly popular among theorists as it was the first pain theory to entertain the idea of a mind-body perspective (Trachsel et al., 2024). However, pain is much more complex than the mind-body relationship can describe. It was not until John D. Loesser noticed commonalities between the interworking’s of the Biopsychosocial Model and factors affecting pain presenting in his patients (nociception, pain, suffering, and pain behaviors) that the Biopsychosocial model began to be applied in pain research (Trachsel et al., 2024). In 2007, a biopsychosocial approach to pain processing, formulated on concepts of the Biopsychosocial Model, was described by Gatchel and colleagues (Gatchel et al., 2007). This approach depicts pain as a unique experience with an etiology governed by a multi-disciplinary relationship between biological, psychological, and social mechanisms (Gatchel et al., 2007). The Biopsychosocial Model as an approach to pain processing is the only pain theory that provides rationale to account for the maladaptive pathology of chronic pain, including its development and continuation (Trachsel et al., 2024). This model goes beyond the physical to account for the psychological and social factors that may attribute to the chronicity of pain after the healing stage ends. For example, biological processes, like increased receptor sensitivity, influence pain processing from a bottom-up process. However, cognitive processes, like predetermined beliefs about pain, can also influence pain processing in a top-down process. Since the pain experience is largely subjective, understanding psychosocial factors at play in the life of the person experiencing it, is key. 9 1.5 Pain and Subjective Well-being in Spinal Cord Injury Subjective well-being (SWB) is a concept defined by Ed Diener that takes into consideration how an individual thinks and feels about their own life (Das et al., 2020). Diener breaks SWB into three core components: positive affect, negative affect, and life satisfaction (Diener et al., 1999). Because the individual components are interrelated, Diener labeled the overarching concept “SWB” to encompass all three components (Diener et al., 1999). Investigating SWB has been helpful in gaining insight into the state of economic, societal, and health of populations (Das et al., 2020; National Research Council Committee on National Statistics, 2013). In the following sections I review literature on components of SWB in people with SCI. As NP and MSK pain arise from different mechanisms and present with different symptoms, their effect on SWB may differ. Where possible, literature is reviewed separately for the two pain types. Where this is not possible (i.e., research has not been published for the two different types of pain), a review of the literature is provided from studies of people with chronic pain in general. Subjective Well-Being: Positive Affect The frequency at which you think positively or negatively is known to impact SWB (Diener, 1984). The term “affect” can be used to describe the frequency of positive or negative thinking. Affect is a momentrary feeling of pleasure (positive affect) or displeasure (negative affect) (Ekkekakis, 2013). Diener argued that operating with a majority positive affect is related to a pleasant emotional experience, referred to as feelings of happiness, joy, contentment, pride, elation, affection, or ecstasy (Diener et al., 1999). One study found that, in general, individuals with SCI reported less positive affect than those who did not have SCI (Salter et al., 2013). We 10 were unable to identify any studies that looked at positive affect and pain in people with SCI or differences in affect for people with musculoskeletal and NP pain types. However, literature on positive affect and chronic pain suggests that there is a negative correlation between pain severity and positive affect (Fredrickson, 2001; Ong et al., 2020) and that positive affect can attenuate pain experiences in clinical and healthy populations by reducing pain sensitivity (Hanssen et al., 2017). Subjective Well-Being: Negative Affect Negative affect includes feelings of guilt, shame, sadness, anxiety, worry, depression, stress, and envy (Diener et al., 1999). A cross-sectional study conducted in 2013 reported on multiple aspects of unpleasant affect in 100 people with SCI (Mann et al., 2013). The authors reported anxiety in more than half of all participants (59%) and depression in 51% of those with severe pain (Mann et al., 2013). In addition, there were trends of poorer health and vitality and higher pain interference with higher levels of pain (Mann et al., 2013). As these trends show low SWB levels and high pain levels in those with SCI, this is evidence to suggest pain may be a largely contributing factor for low levels of SWB in this population. It has been suggested that pain and affective states are interconnected, where affect has been shown to have bidirectional pain modulation effects (Janssen, 2002). That is, increasing pain has been shown to be associated with increasingly negative affect. In addition, pain modulation mechanisms are suggested whereby negative affect magnifies chronic pain, leading to pain sensitivity (Janssen, 2002). This suggestion is further supported by the Biopsychosocial approach to pain (Figure 1), where the interplay between cognitive and physical factors are important to consider during pain treatment (Gatchel et al., 2007). 11 In a study conducted in people with SCI and MSK pain, the authors found correlations between low quality of life and high pain catastrophizing (a negative affective response) after SCI (Finley et al., 2021). In people with SCI who have NP, evidence indicates that negative affective states are related to negative mood (Cairns et al., 1996; M. P. Jensen et al., 2007). There is little literature describing differences in affect between those with chronic NP and MSK pain in SCI. A recent study reported that individuals with SCI and chronic NP experience lower levels of quality of life along with higher levels of depression, pain interference, and pain catastrophizing than those with SCI and MSK pain (Canori et al., 2024). Similarly, two other recent reviews suggest that NP has more of an impact on quality of life compared to MSK types of chronic pain, indicated by lower quality of life in NP populations (Rodrigues et al., 2021; Szewczyk et al., 2022). As these findings are recent, potential explanations are not discussed; however, we hypothesize that the uncontrollable nature and array of symptomology of NP could be leading to lower quality of life through greater pain catastrophizing. NP is known to provoke individuals to adopt an external locus of control (Torta, 2017), which is the belief that you cannot control outcomes of your life. Having an external locus of control is known to decrease well-being (Kesavayuth et al., 2022). Therefore, we provide this explanation as a potential suggestion for why individuals with chronic NP may report lower levels of SWB than those with chronic MSK pain. To summarize, the frequency with which an individual experiences feelings of pleasant and unpleasant affect are indicators of SWB. Literature indicates low levels of positive affect and high levels of negative affect, including anxiety and depression in those with SCI and chronic pain. In the limited studies that compared between pain types, greater negative affect (including pain catastrophizing and depression) and lower quality of life was found in individuals with 12 chronic NP compared to those with chronic musculoskeletal pain (Canori et al., 2024; Rodrigues et al., 2021; Szewczyk et al., 2022). However, only one of these studies was conducted in people with SCI, and is limited by its small sample size of 17 (Canori et al., 2024). Subjective Well-Being: Life satisfaction Life satisfaction is the third component of SWB (Diener, 1984). According to the American Psychological Association, life satisfaction is the extent to which an individual finds meaning, quality, or richness with their life (American Psychological Association, 2018). Those with SCI report low levels of life satisfaction compared to the average of the population (Post & Van Leeuwen, 2012). However, in a survey conducted with 191 people with SCI, those with pain reported even lower life satisfaction than those with SCI and no pain, which is thought to be attributed to higher levels of anxiety and depression reported in the pain group (Budh & Österåker, 2007). In a recent cross-sectional study, there were significant negative correlations between pain outcomes and life satisfaction, where authors suggested improvements in pain can lead to improvements in life satisfaction and vice versa (Williams et al., 2024). Importantly, in a longitudinal study involving 676 people with SCI, lower levels of life-satisfaction were predictors of mortality; with significant associations between upward trends of life satisfaction and lower odds of mortality among participants (Cao et al., 2023). This speaks to the importance of improving life satisfaction in this population. To our knowledge, there are no studies that compare life satisfaction between those with chronic NP and musculoskeletal pain and SCI. To summarize, there is a need for more investigation on SWB in chronic NP and musculoskeletal pain in people with SCI. To target improvements in SWB in these populations, we need to first describe and understand differences and/or similarities in affect and life satisfaction. Understanding differences in affect and life satisfaction in those with chronic NP 13 versus chronic musculoskeletal pain will allow for more insight into which SWB components should be targeted in future interventions of the specific pain types, improving specificity and efficiency of potential treatments. 1.6 Benefits of Physical Activity Caspersen’s definitions of physical activity, exercise, and physical fitness have been used since 1985 to distinguish these concepts for health-related research (Caspersen et al., 1985). Physical activity is described as “any bodily movement produced by skeletal muscles” (Caspersen et al., 1985). When referring to physical activity levels, we take into consideration activities like commuting, household chores, as well as recreational and leisure time activities. Physical activity differs from exercise, which is defined as “a subset of physical activity that is planned, structured, and repetitive” (Caspersen et al., 1985). In people with SCI, recommended types of exercise include aerobic training, such as arm ergometry and wheeling their wheelchairs, as well as resistance training, including strength building movements (Martin Ginis et al., 2018). Any activity requiring physical exertion that people choose to do in their free time is referred to as Leisure Time Physical Activity (LTPA) (Bouchard et al., 1994). As such, LTPA encompasses time spent playing sports, exercising, and going for a leisure walk or a wheel outside of what is necessary for daily activities of living (Bouchard et al., 1994). There is accumulating evidence to suggest that physical activity participation promotes positive changes in physiological measures, such as fitness, in people with SCI (Van Der Scheer et al., 2017). The Scientific Exercise Guidelines for SCI were created to determine the minimum exercise dose required to elicit these health improvements (Martin Ginis et al., 2018). Beyond physiological benefits, those with SCI who are physically active may benefit from improvements in overall well-being, as suggested by a recent meta-analysis. Findings indicated positive effects 14 of exercise interventions on subjective, psychological, and social well-being as well as health-related quality of life in people with SCI (Ponzano et al., 2024). In addition to both physiological and psychological health benefits, a recent systematic review reported that exercise interventions reduced pain in adults with chronic pain (Palmer et al, 2023). Authors discussed the dual-benefitting effects of exercise, reducing pain and altering brain function in pain-related brain regions of adults with chronic pain (Palmer et al, 2023). In addition to this, a scoping review of the effects of physical activity interventions on chronic pain and SWB in people with SCI found reductions in pain alongside improvements of SWB post exercise for most studies (Todd, Lawrason, et al., 2021). In the wider population, there is a general tendency to use movement to relieve discomfort, with new trends emerging recommending stretching during lunch breaks to alleviate MSK discomfort (Alqhtani et al., 2023). Evidence can be found in Babault and colleagues’ study from 2021 reporting findings from a survey conducted on 3546 participants in physical activity programs, where 89.3% of people rely on stretching exercises to reduce muscle soreness (Babault et al., 2021). Studies suggest that like the general population, people with chronic MSK pain also use range of motion and mobility exercises to relieve muscle and joint pain (Tallawy et al, 2021). However, authors suggest steering away from excessive levels of physical activity that could result in overuse injuries (Tallawy et al, 2021), which can cause pain, therefore negating the very benefits people are trying to achieve. The possibility of overuse injuries or pain during movement can lead to increased pain catastrophizing and individuals avoiding physical activity (Bordeleau et al., 2022); as high levels of pain are associated with high levels of kinesiophobia in people with chronic pain (Larsson et al., 2016). 15 Research speaking to the effects of physical activity for chronic NP is limited compared to that of research reporting the effects of physical activity for chronic MSK pain (Leitzelar & Koltyn, 2021). In people with SCI and chronic NP, two studies conducted on the acute effects of exercise on chronic NP suggest that even a single bout of exercise may provide pain-alleviating and mood-boosting effects, although there was inconsistency across participants (Todd, Van Der Scheer, et al., 2021; Todd & Martin Ginis, 2018). Furthermore, one study was conducted looking at correlations between pain and min/week of exercise in athletes and recreational exercisers with SCI and NP (Todd et al., 2023). Interestingly, authors found that moderate to high levels of exercise may exacerbate NP in athletes (Todd et al., 2023). To our knowledge, only one study has compared physical activity levels among people with SCI and chronic MSK or chronic NP (Canori et al., 2024). In a cross-sectional study involving 17 individuals with SCI, authors found greater pain intensity, pain interference, and pain catastrophizing in those with NP than MSK pain (Canori et al., 2024). In addition, they found that those with NP did more minutes of moderate to vigorous physical activity per day than those with MSK pain (Canori et al., 2024). Significant associations between average minutes per day of physical activity and pain levels in those with chronic NP were found, whereby people who did more physical activity reported less pain compared to those who did less physical activity (Canori et al., 2024). In those with chronic MSK pain, no significant associations between pain and physical activity levels were found. However, a curvilinear relationship was proposed whereby physical activity is associated with lower pain until it reaches a certain level, and then it becomes associated with greater pain due to overuse (Canori et al., 2021). As previously noted, these authors also reported higher levels of depression, lower quality of life, and higher pain interference and pain catastrophizing in people with chronic NP 16 compared to those with chronic MSK pain (Canori et al., 2024). The authors recommended replication of their study with a larger sample as detecting significant differences across pain types, and generalizing across injury levels was not achievable with their sample size of 17 (Canori et al., 2024). Nevertheless, their findings indicate that there may be differences in the relationships between pain, SWB, and physical activity levels between people with SCI who have different pain types (MSK, NP). In summary, there is little reported on the levels of pain, SWB, and physical activity in people with different SCI-related pain problems (NP and MSK). As differences exist between chronic NP and MSK pain development, symptomology, and epidemiology, differences in pain severity, pain interference, (positive and negative) affect, life satisfaction, and LTPA in these two populations could also be expected. Further research comparing these variables in people with SCI and MSK and NP pain is needed to advance a more fulsome understanding of NP and MSK pain in people with SCI and ultimately, to improve pain treatments. 1.7 Purpose Understanding differences between levels of pain, SWB, and LTPA in those with chronic NP and chronic MSK pain is crucial for the development of future practices and clinical recommendations for management of different pain types, as well as to improve the quality of life of individuals with SCI. Therefore, the overarching purpose of this thesis is to describe and compare differences between pain, SWB, and LTPA across pain groups. 17 Chapter 2. Hypotheses Hypothesized Differences Between Pain Groups 2.1 Primary Hypothesis. Levels of Pain Recent findings indicate that individuals with SCI and NP present with higher pain levels than those with MSK pain (Canori et al., 2024). For this reason, we hypothesize that the NP group will report greater pain severity and interference than the MSK group. 2.2 Secondary Hypothesis. Levels of Subjective Well-Being Chronic pain is extremely debilitating. However, with NP being random in nature (i.e., uncontrollable), as well as presenting as an array of different symptomology (such as tingling, shooting, stabbing pains, and/or pins and needles), it often provokes individuals to view the world through the lens of an external locus of control (Torta, 2017), which is known to decrease well-being (Kesavayuth et al., 2022). Furthermore, the limited research comparing NP and MSK pain shows a trend of those with NP experiencing lower SWB than those with MSK pain (Canori et al., 2024). For these reasons, we expect those with chronic NP to have greater stress and lower scores on satisfaction with life and positive affect than those with chronic MSK pain. 2.3 Tertiary Hypothesis. Levels of Leisure Time Physical Activity There is a lack of research identifying and interpreting differences between leisure time physical activity in those with chronic NP and chronic MSK pain and SCI. Therefore, it was difficult to formulate a hypothesis for this variable. Rationalizing that those who experience more pain and worse subjective well-being may be less likely to participate in physical activity, we hypothesized that those with chronic NP will participate in less physical activity than those with chronic MSK pain. 18 Chapter 3. Methodology 3.1 Study Design This is a cross-sectional study utilizing a subset of baseline data from the Exercise guideline Promotion and Implementation in Chronic SCI (EPIC-SCI) trial. EPIC-SCI is a single-blind, double arm, pragmatic randomized controlled trial (RCT) testing the effects of exercise on pain in adults with SCI (Martin Ginis et al., 2020). The design of EPIC-SCI, including the testing protocol used in this study, was a collaborative effort involving over 150 people with SCI and 50 SCI Clinicians and was informed by integrated knowledge translation principles. All testing took place at the University of British Columbia (UBC) Vancouver and Okanagan Campuses in Canada. For this cross-sectional study, only pain, SWB, and LTPA are relevant to our research question; therefore, assessment of other outcomes that were measured for the larger trial will not be discussed. For a list of all variables and outcome measurements included in this study, please see Table 1 below. 19 Table 1. Outcome measures for pain, SWB, and LTPA. Study Variable Outcome Measure Score Pain Pain Interference Pain Severity of worst pain problem International SCI Basic Pain Dataset Score out of 10 Score out of 10 Leisure Time Physical Activity Leisure Time Physical Activity Questionnaire for SCI Mild min/day Moderate min/day Heavy min/day All LTPA Subjective Well-Being Negative Affect Positive Affect Satisfaction with Life Perceived Stress Scale SCI-QoL Positive Affect and Well-Being Diener’s Satisfaction with Life Scale Score from 0-49 Score is a standardized T-Metric: 50 ± 10 (mean ± std deviation) Score from 5-35 3.2 Participants, Sample Size, and Effect Size Calculation The desired demographic of this study are adults (≤18 years of age) with chronic SCI (≤12 months post-injury) who experience either chronic neuropathic pain and/or chronic musculoskeletal pain. Participants were recruited through social media, website, email, communications with previous study participants, advertising through community partner organizations, and word of mouth. Target enrolment was 84 participants, including men and women with SCI(Martin Ginis et al., 2020); however, after all recruitment efforts were exhausted, the final sample size was 50 participants. A two-group comparison using ANOVA with an n of 50 participants and a power of 0.80. can detect a medium to large effect at a=0.05 (J. Cohen, 1992). 20 3.3 Inclusion and Exclusion Criteria Inclusion Criteria To participate in this study, participants had to be adults 18 years or older with a traumatic or non-traumatic SCI, 12 months or longer following injury, with AIS impairment scale classification from A-D presenting and injury levels from C-3 or below. Participants had to be reporting chronic musculoskeletal or chronic neuropathic pain, otherwise described as pain persisting or recurring for three months or more (Treede et al., 2019). Participants would also be included only when a physician approved them for a maximal exercise test. Due to the objective of the primary exercise trial, only those who are not meeting the SCI exercise guidelines were included (Martin Ginis et al., 2018). Exclusion Criteria Participants who met the following criteria were excluded from this study: non-MSK or NP related chronic-pain (incl. abdominal pain, headaches), pregnancy, and insufficient diaphragmatic control to do upper-body exercise (as necessary for exercise testing). Furthermore, anyone who was a hospital in-patient at time of enrolment, had been previously informed of a cognitive impairment, or whose English proficiency was not sufficient to complete questionnaires and communicate with research staff was excluded. Those without access to a phone, and/or located outside driving distance of two research sites were also excluded from this study. Lastly, people who met both the aerobic and strength training guidelines were excluded (Martin Ginis et al., 2018). 3.4 Study Protocol Firstly, potential participants were contacted to do familiarization and screening with a research coordinator over the phone. After eligibility was confirmed, participants reviewed 21 detailed study information and then provided informed consent after they read and understood the consent form. Participants were then enrolled in the study and invited complete questionnaires via REDCAP and an over the phone interview. Many outcomes were assessed; however, only those relevant to this thesis will be described next. 3.41 Self-Report Questionnaires Demographic Information Demographic information including age, sex, gender, ethnicity, marital status, work status, AIS classification, cause of injury, time since injury, and time since onset of pain was collected at the beginning of the 45-minute self-report questionnaire in the form of a demographic form via REDCAP. For the first nine participants, questionnaires were done in-person on a computerized tablet. If participants required assistance using the tablet to do so due to any reason (e.g, limited hand function), a staff member assisted them in doing so. All subsequent participants did the questionnaires at home via REDCAP due to protocol changes associated with COVID-19. If AIS classification was not known, the following multi-option AIS classification question was asked which coincides with AIS classifications A (option 1), B (option 2), C (option 3), D (option 4), and E (option 5);“Which best describes you: 1) No feeling or movement below level of injury, 2) Feeling all the way down to your rectum but no use of muscles, 3) Limited movement/ muscle contractions below level of injury but these serve no useful function, 4) Functional, but not necessarily full use of at least half of the muscle groups below level of the injury, or 5) Feeling and movement is normal below level of injury”. 22 Leisure Time Physical Activity The Leisure Time Physical Activity Questionnaire for people with SCI (LTPAQ-SCI) (Martin Ginis et al., 2012) was used to measure time spent doing leisure activity. The LTPAQ-SCI is a self-report assessment of LTPA that was created specifically for use in SCI populations. It has been assessed for validity and reliability in samples of people with SCI (Martin Ginis et al., 2012, 2021). The LTPAQ collects self-reported data on frequency (day/week), intensity (mild/moderate/vigorous), and duration (time/day) of LTPA for all aerobic activities performed over the last seven days. Additionally, days per week, number of exercises, and number of sets of strength training performed over the last seven days was collected. Time spent doing aerobic LTPA of all intensities (mild, moderate, heavy) for all seven days was summed to calculate total LTPA for each participant. Subjective Well-Being: Positive Affect, Negative Affect, and Life Satisfaction. The first component of Subjective Well-Being, Positive Affect, was assessed using the SCI Quality of Life (SCI-QOL) 10-item measure of Positive Affect and Well-Being (Bertisch et al., 2015; Tulsky et al., 2015). This measure was developed specifically for assessing positive affect in SCI samples (Bertisch et al., 2015). Ten items are presented and responses are made on a 5-point Likert-type scale ranging from 1 (“never”) to 5 (“always”). The total score is calculated by summing all 10 items and converting to a T score metric with a standardized mean of 50 and standard deviation of 10, which represents the “average” responses in the SCI population, with greater values indicative of better affect and well-being (Bertisch et al., 2015). The second component of Diener’s Subjective Well-Being concept, Negative Affect, was assessed using the Perceived Stress Scale (S. Cohen et al., 1983), as stress is a negative affective response that is high in those with SCI pain (Tran et al., 2016). This scale has previously been 23 applied to samples of those with SCI to give insight into long term coping ability after SCI (Gerhart et al., 1999). To score it, we must first account for directionality in which the question was asked, which includes reversing items 4, 5, 7, and 8. Scoring of the Perceived Stress Scale was then calculated by summation of all the individual responses; scores can range from 0-49 with a higher value indicating higher levels of stress (S. Cohen et al., 1983). Lastly, Life Satisfaction was assessed using Diener’s Satisfaction with Life Scale (Diener et al., 1985). Diener’s Satisfaction with Life Scale constitutes five items that are scored on a Likert scale from 1 (strongly disagree) to 7 (strongly agree) (Diener et al., 1985). Each response was summed to calculate a total score of life satisfaction that ranges from 5-35. Higher scores indicate higher life satisfaction and lower scores indicate a lower satisfaction with life (Diener et al., 1985). 3.4.2 Pain Interview Prior to in person testing, participants were scheduled for a 30-minute structured interview on NP and MSK pain with a trained pain accessor over the phone or using UBC’s videoconferencing software (Zoom). The 30-minute interview involved administering both the International SCI Pain Basic Dataset and the Doleur Neuropathique 4 (DN4). First, descriptive information was collected using the International SCI Pain Basic Dataset (Widerström-Noga et al., 2014), which measures overall pain interference, intensity, and collects detailed information about location, type, and onset of up to three pain problems over the last 7 days (Widerström-Noga et al., 2014). The International SCI Pain Basic The International SCI Pain Basic Dataset has demonstrated acceptable reliability and validity in clinical and research settings (M. P. Jensen et al., 2010). To measure pain 24 interference, three questions are asked pertaining to day-to-day activities, mood, and sleep over the last 7 days. Responses are made on a scale ranging from 0 (no interference) to 10 (extreme interference). Following this, up to three pain locations and their characteristics are described to classify pain locations and types. For the purpose of this study, only data pertaining to the first “worst” pain problem will be used in data analysis. Intensity of the first pain location is rated from 0 (no pain) to 10 (pain as bad as you can imagine). As such, the pain interference and intensity values (each scored out of 10) were the outcome measures of pain used for analysis. A higher score is indicative of greater interference and intensity, respectively (Widerström-Noga et al., 2014). Other information collected includes the date of onset and any treatments currently being used for the pain problem. After a pain location was identified by the participant, a series of investigative questions were asked in order to classify the type of pain. These questions are in line with the recommended classifications and associated descriptions given by authors of the questionnaire (Widerström-Noga et al., 2014). Examples of question topics include asking about whether the pain is dull or aching (MSK) versus tingling and burning (NP), localized (MSK) versus widespread (NP), aggravated by movement (MSK), more prevalent at the end of the day (MSK) versus random and spontaneous occurrence (NP). Distinguishing questions were asked until saturation (i.e., meaning the pain accessor was continuously receiving answers in line with the same pain type, therefore confident to choose a pain classification). If pain was presenting symptoms of NP and NP was chosen as the response on the International Basic Pain Dataset, the DN4 interview was conducted next to verify the existence of NP. 25 Douleur Neuropathique 4 The Douleur Neuropathique 4 is a tool used to verify the existence of NP based on symptomology. It has shown appropriate reliability (Hardt et al., 2023) and validity (Ríos-León et al., 2024) and has been previously applied to SCI populations (Hallström & Norrbrink, 2011). The DN4 is a ten-question questionnaire asking about presence of ten known NP pain symptoms. Each “yes” is counted as one point out of ten and a score of four or greater indicates probability of the presence of NP. It was used to verify that any pain classified as NP on the International SCI Basic Pain Dataset by a trained pain accessor was indeed NP. A score of 4 or greater is the cut off to determine whether enough symptoms are present to indicate the probability that there is NP. Only the first (worst) pain problem was further assessed using the DN4 for verification of NP. 26 Chapter 4. Data Analysis 4.1 Pain Classification After data was collected for all participants, each participant’s primary pain type was coded individually. Participants in the study were categorized based on their primary (worst) pain problem identified on the International Basic Pain Dataset. Those whose primary pain problem is musculoskeletal pain were categorized as “MSK group”. Those whose primary pain problem was neuropathic pain and who also report 4 or more symptoms of neuropathic pain on the DN4 (resulting in a score of 4 and above) were categorized as “NP group”. For various reasons, including accessor error or uncertainty, some participants did not have their pain type reported in the International Basic Pain Dataset. For these individuals, pain location, symptomology, and any additional comments available on the International Basic Pain Dataset were reviewed on REDCAP to assign their primary pain type. Those who did not have data entered about pain type, location, or symptomology were categorized as “No Data”. Lastly, participants who reported pain symptoms that we were unable to distinguish were coded as “Unknown”. 4.2 Analysis Plan and Treatment of Missing Data Descriptives were calculated for each study variable (Table 1) in each group (MSK group or NP group) using IBM SPSS version 27 (SPSS Inc., Chicago, IL.). Correlations between demographic variables and outcome measures were tested to determine covariates. Internal consistency and reliability of scales were checked by calculating Cronbach’s alpha and compared to the benchmark for acceptability (0.7) (Nunnally, 1978). Assumptions of ANOVA were tested prior to analysis. Averages were reported and compared between groups (NP group and MSK group) using ANOVA to address primary, secondary, and tertiary hypotheses. Effect size 27 calculations were done and interpreted as recommended: small (0.2), medium (0.5), and large (0.8) (Carson, 2004). Missing data was reported and where appropriate, missing data was replaced with the mean of the corresponding group or the next closest value -1. 28 Chapter 5. Results 5. 1 Participant Demographic Characteristics In this study, 87 people were screened for eligibility, while 50 of those participants met inclusion criteria and went on to be enrolled. Of those 50 participants, 4 were excluded prior to data analysis due to their primary pain not being clearly identifiable as NP or MSK (therefore unable to be categorized into either the NP or MSK group). Out of those 46, 34 (74%) were males and self-identified as men, while 12 (26%) were females and self-identified as women. All participants were people with SCI between the ages 22-73, with an average age of 50.3 +/- 14.2, not meeting physical activity guidelines for people with SCI, with sufficient diaphragmatic control to do upper-body exercise. They all had English proficiency, reported no previous cognitive impairment and lived within driving distance to one of two research sites in British Columbia. The 46 eligible participants were categorized based on their primary pain problem: NP group (n= 34) or MSK group (n=12) (Figure 1). Demographic characteristics for each group were reported as per recommendations by the Cochrane PROGRESS- Plus Guideline (Cochrane, 2024) for identifying and reporting characteristics that stratify social health determinants and are presented in Table 2. Independent samples t-tests revealed differences in quantitative demographic criteria (age, time since injury) between groups. 29 Figure 1. Flow of Participants Through Study Assessed for eligibility (n= 87) Excluded (n= 37) - not meeting eligibility (n=37) Eligible (n=50) Categorized to NP group (n=34) Excluded (n=4) - could not be classified as having either NP or MSK pain (n=4) Categorized to MSK group (n=12) Enrollment Categorization Analysis Analysed (n=34) Analysed (n=12) 30 Table 2. Participant Demographic Characteristics for the Neuropathic and Musculoskeletal Pain Groups Neuropathic n=34 Musculoskeletal n=12 Age (years) (n) 53.39 +/-14.2a 41.8 +/- 10.5 Sex Male 26 8 Female 8 4 Gender Man 26 8 Woman 8 4 Ethnicity Caucasian 29 10 Black 1 0 Asian 4 2 Marital Status a Single 10 5 Common law 6 3 Married 11 2 Divorced 6 1 Widowed 1 0 Work Status Employed full-time (40hr/wk) 4 2 Employed part-time (<40hr/wk) 0 1 Unemployed (looking) 1 2 Unemployed (not looking) 2 1 Student 2 1 Retired 12 5 Self-employed 7 0 Unable to work 5 0 Other 1 0 Education Level High School 2 0 Some college 5 6 Some university 4 0 College degree 10 2 University degree 13 4 ASIA Classification A 11 6 B 1 3 C 5 2 D 16 1 31 Note: amissing 1 data point, b missing two data points, cmissing three data points. 5.2 Preliminary Analyses Data were screened prior to analysis for entry errors, outliers, and missing data. As expected, due to participants having full autonomy to disclose or withhold any information they chose not to share, a couple of participants did not complete all of the questionnaire measures. Variables with missing data are identified in Table 3. As recommended by Tabachnick and Fidell, missing data for mild intensity LTPAQ of one participant was replaced with the mean of the group (Tabachnick & Fidell, 2007). Regarding outliers, one outlier was identified for each measure of physical activity in the LTPAQ (i.e., mild, moderate, and heavy intensity LTPA). Each outlier was replaced with the next highest data point on the distribution plus one, as recommended (Tabachnick & Fidell, 2007). Descriptive statistics were computed to characterize the distribution of data and skewness and kurtosis. Results are presented in Table 3. Cronbach’s alpha was calculated to assess Internal Reliability Consistency of each measure that was calculated by a multiple item questionnaire (Perceived Stress Scale, Positive Affect and Well-Being, and the Satisfaction with Life Scale) Neuropathic n=34 Musculoskeletal n=12 E 1 0 Level of Injury a Paraplegic 21 6 Tetraplegic 12 6 Time Since Injury (years) 13.71 +/- 12.6 24.3 +/- 10.7 Cause of Injury Motor vehicle accidents 15 5 Sports accidents 7 1 Traumatic wounds 1 Illnesses 5 3 Falls 0 2 Other 6 0 Time Since Pain Onset (years) 10.7 +/- 11.3 b 8.0 +/- 5.7 c 32 and is presented in Table 3. All Cronbach’s alpha results were above the threshold of acceptable values for internal reality consistency (a>0.7)(Nunnally, 1978). All three questionnaires, the Perceived Stress Scale (a=0.73), the Life Satisfaction Scale (a=0.88) and Positive Affect and Well-Being (a=0.9) were above the threshold of acceptability. Preliminary analyses were computed to test the assumptions of ANOVA, including Shapiro Wilks test for Normality and Levene’s Test for Homogeneity of Variances for all measures. Results are presented in Table 3. Level of significance was set at p< 0.05. Normality was a concern for the NP group’s pain severity scores, MSK group’s pain interference scores, NP group’s perceived stress scale sores, MSK positive affect and well-being scores, as well as both groups’ scores for mild, moderate, and heavy intensity LTPA, as well as NP group total LTPA. In attempt to correct for non-normalcy and equalize differences in variance for minutes of total LTPA, several data transformations were applied including logarithm and square root transformations. Results are presented in Appendix B. However, neither transformation rectified these concerns, therefore raw data was used for subsequent analyses of all variables. Linear regression models were computed to identify possible covariates for the hypothesis tests. Regression models identified the following covariates: fatigue as a significant correlate of Positive Affect and Well-Being and Satisfaction with Life, and age as a significant correlate of Heavy Intensity Leisure Time Physical Activity. However, as age is significantly different between the MSK and NP groups, it will not be used as a covariate. A covariate should not be used if the mean value differ between groups and the participants were not randomly allocated to those groups (Miller & Chapman, 2001). 33 Table 3. Tests for assumptions of ANOVA including Skewness, Kurtosis, Shapiro-Wilks test of Normality and Levene’s test of Homogeneity of Variance. Group n Skewness Kurtosis Shapiro- Wilks Levene’s Test Cronbach’s alpha Pain Severity NP MSK 33* 11* 0.108 0.369 -1.397 1.454 0.002 0.410 0.145 NA Pain Interference NP MSK 33* 11* 0.349 -0.405 -0.513 -0.453 0.286 0.015 0.176 NA Perceived Stress Scale NP MSK 33* 12 0.797 0.227 0.494 -0.222 0.037 0.483 0.215 0.725 Positive Affect and Well Being NP MSK 32* 12 -0.183 -2.064 -0.315 4.902 0.524 0.005 0.669 0.934 Satisfaction with Life Scale NP MSK 34 12 0.171 -0.405 -0.901 -0.296 0.391 0.963 0.760 0.882 Mild LTPA NP MSK 34 11 2.178 1.376 4.786 0.872 <0.001 0.004 0.071 NA Moderate LTPA NP 34 2.346 6.332 <0.001 0.140 NA MSK 12 1.044 0.285 0.036 Heavy LTPA NP MSK 34 12 2.685 1.048 6.390 -0.906 <0.001 <0.001 0.150 NA All LTPA NP MSK 34 12 1.514 0.549 1.207 -1.205 <0.001 0.097 0.029 NA Note: *= missing data. 5.3 Hypothesis Tests Results for the hypothesis tests, including descriptive statistics (means and standard deviations), Analysis of Variances (ANOVAs) and Analysis of Covariances (ANCOVAs) and their F- and p-values are presented in the following section. ANOVA results for all variables are presented in 34 Table 4 whereas ANCOVA results are presented in Table 5. Effect size calculations were done for all variables and are also presented in Tables 4 and 5. Primary Hypothesis: Levels of Pain 1) Pain severity. A general linear model ANOVA using the International Spinal Cord Injury Pain (ISCIP) Basic Data Set measurement of Pain Severity as the dependent measure, yielded a significant difference in pain severity between groups F (1, 42) = 5.295, p= 0.026, d= 0.798. The NP group had significantly greater pain severity scores and the difference/effect size was classified as large. This analysis supports our primary hypothesis that those with NP would have greater levels of pain severity. 2) Pain interference. The analysis of the ISCIP measurement of Pain Interference of Daily Activities yielded no statistically significant differences between groups, F (1,42) =1.276, p=0.265, d=0.393. This analysis does not support our hypothesis that those with NP would have greater levels of pain interference. However, the NP group tended toward greater pain interference, and the difference was a small to medium effect size. Secondary Hypothesis: Levels of Subjective Well-Being 1) Negative affect: a general linear model ANOVA and effect size calculation were conducted for the Perceived Stress Scale F (1, 43) = 1.917, p=0.173, d=0.466. The difference in means between groups was not statistically significant. This analysis does not support our secondary hypothesis that those with NP would have significantly greater levels of stress. However, there was a medium-sized effect with the NP group reporting greater levels of stress than the MSK group. 2) Positive affect. Univariate ANCOVAs using fatigue as a covariate were conducted for both Positive Affect and Well-Being and Satisfaction with Life. There was no statistically significant difference between groups in Positive Affect and Well-Being scores, F (1, 42) =0.245, p=0.623, d=-0.25 and fatigue was a significant covariate (p=0.003). There was a small effect 35 where those in the NP group had greater Positive Affect and Well-Being scores than the MSK group. 3) Life satisfaction. Lastly, there was no statistically significant differences in Satisfaction with Life scores, F (1, 43) = 2.009, p= 0.164, d=0.37 and fatigue was a significant covariate (p=0.008). This analysis does not support our hypothesis that those with NP would have significantly lower scores of Satisfaction with Life than those with NP. However, there was a small-medium effect found whereby those with NP had lower life satisfaction. Tertiary Hypothesis: Levels of Leisure Time Physical Activity A general linear ANOVA and effect size calculation was conducted for minutes of mild intensity LTPA per week F (1, 42) = 1.730, p=0.192, d=0.454. No significant differences were found between groups. A medium-sized effect was found whereby those in the NP group had greater total minutes of mild intensity physical activity per week. Similar results were found for minutes of moderate intensity LTPA, F (1, 44) = 0.520, p=0.475, d=0.263. There was no statistically significant difference between groups, but a small effect size was found, whereby those in the NP group reported more minutes of moderate LTPA. For minutes of heavy intensity LTPA F (1,44) = 1.585, p=0.215, d=0.359, there was also no statistically significant difference between groups. However, there was a small to medium effect and those with MSK had more minutes of heavy intensity LTPA than participants with NP. When total weekly minutes of LTPA were compared between groups we also found no difference between groups F (1,44) = 0.765, p=0.387, d=0.357. However, the NP group had more minutes of LTPA and a “small to medium” effect size was found. This analysis does not support our tertiary hypothesis, that there would be greater LTPA in those with MSK pain. 36 Table 4. Means and standard deviations for the NP and MSK groups, ANOVA results and effect sizes. Note: *= significant at p<0.05, min= minutes. NP mean (SD) MSK mean (SD) F value p value Cohen’s d Effect Size Pain Severity 5.21 (1.80) 3.82 (1.54) 5.295 0.026* 0.798 Large Pain Interference 4.36 (2.49) 3.45 (1.64) 1.276 0.265 0.393 Small-Medium Perceived Stress Scale 14.18 (6.86) 11.17 (5.11) 1.917 0.173 0.466 Medium LTPAQ Mild intensity aerobic training min /week 114.56 (168.45) 45.91 (68.19) 1.730 0.195 0.454 Medium LTPAQ Moderate intensity aerobic training min/week 81.91 (122.38) 52.92 (59.18) 0.616 0.437 0.263 Small LTPAQ Heavy intensity aerobic training min/week 17.88 (45.33) 35 (54.02) 0.141 0.709 0.359 Small-medium LTPAQ Total aerobic training min/week 195.44 (268.88) 110.00 (108.06) 1.133 0.293 0.357 Small-Medium 37 Table 5. Adjusted means and standard deviations for the NP and MSK groups, ANCOVA results and effect sizes. NP MSK F P Cohen’s d Effect Size Covariates (p-value) Positive Affect and Well-Being 38.44 (7.15) 36.67 (6.88) 0.245 0.623 -0.25 Small *Fatigue (p=0.003) Satisfaction with Life Scale 20.76 (7.45) 23.50 (7.23) 2.009 0.164 0.37 Small-medium *Fatigue (p=0.008) Note: * = Covariates are significant at p<0.05. Values are adjusted for the significant covariate. 5. 4 Results Summary A summary of results at the hypothesis level and by individual variable is presented in Table 5. Table 6. Summary of Results including all variables and hypotheses. Individual Measures Significance Effect Size Hypothesis 1: Levels of Pain Pain Severity Pain Interference √ X Large Small-medium Hypothesis 2: Subjective Well-Being Perceived Stress Scale Positive Affect and Well-Being Satisfaction with Life Scale X X X Medium Small Small-medium Hypothesis 3: Leisure Time Physical Activity Minutes of Leisure Time Physical Activity per week X Small-medium 38 Chapter 6. Discussion The primary purpose of this study was to compare levels of pain severity and pain interference in people with SCI who have chronic NP and those who have chronic MSK pain. A secondary purpose was to compare aspects of subjective well-being, including positive affect, life satisfaction, and perceived stress between those with NP versus MSK pain. The third purpose was to compare LTPA between MSK and NP pain groups. The primary finding was that pain severity was significantly greater in those with chronic NP than those with chronic MSK pain (clinically meaningful difference). Although there were no other statistically significant differences between groups, effect size calculations indicated meaningful differences between groups, including greater pain interference (clinically meaningful difference-small to medium effect), more stress (medium effect), and lower satisfaction with life (small to medium effect), in those with NP than those with MSK. And yet, participants with NP also had greater positive affect (small effect) and more minutes of physical activity per week (small to medium effect) than those with MSK. To our knowledge, this is only the second study (after (Canori et al., 2024) to distinguish between pain phenotypes in individuals with SCI and identify differences in biopsychosocial aspects of health between those with chronic MSK and chronic NP. While Canori et al.’s study reported differences between groups, they did not discuss or interpret them because it was not a primary purpose of the study (Canori et al., 2024). Therefore, this is the first study to focus on identifying differences between chronic pain types and to consider why such differences may exist, as well as the implications. This study provides insights into pain, well-being, and physical activity that have not yet been examined and will therefore be great use to future work in this field. 39 6.1 Providing Context and Meaning to Statistical Results It is important to contextualize statistical findings as context provides insight into the meaning of findings in the real world. As such, we tested for significance (based on p-values < .05) and calculated effect sizes (Cohen’s d) for all between-groups comparisons. Despite only finding one significant difference, we found clinically meaningful differences in pain, as well as effects of varying sizes between groups for all other outcomes. In the following sections, much of the discussion is based on interpretation of the effect sizes as effect sizes provide insight into the meaningfulness of results. Effect sizes provide information about meaning because they describe the size of the difference between groups, whereas a p-value tells us about the likelihood that a difference exists between groups (and is not due to chance). As such, there may be a difference between groups that is statistically significant (p-value < 0.05), but not meaningful to participants. For example, if there is a miniscule difference (no effect) in pain between groups but the sample size is very large, it is possible that the statistically significant result does not have meaningful impact in the participant’s life. The opposite is true, as there may not be a significant difference between groups (p-value > 0.05) but an effect that is meaningful to participants in the context of the study or in clinical settings in the real world. For example, in smaller sample sizes like the one in this study, it is common to be underpowered (unable to yield a statistically significant difference); however, the magnitude of the change may be meaningful to the participant’s life. For example, it has been reported that even a 0.1 decrease in standard deviation of the General Perceived Stress Scale is comparable in importance to enduring the loss of a loved one (Testa & Simonson, 1996). As such, even a small difference between groups could be extremely meaningful to 40 participants and have a significant impact on their daily life, regardless of a significant difference. For pain measures, there is a benchmark for a clinically meaningful difference. The benchmark is a 30% difference in pain score between groups (or over time in a longitudinal study). This difference represents the difference in pain score that is deemed to present with clinically meaningful impacts to one’s life and daily function. We were unable to identify benchmarks for clinically meaningful differences in SWB outcomes, therefore clinical meaningfulness is not discussed for SWB outcomes. The importance of interpreting the contextual meaning of results has been well documented (Crosby et al., 2003). Therefore, the results are interpreted in terms of their effect sizes (including small, medium, large effects) and clinical meaningfulness (for pain) in the following sections. 6.2 Pain Severity and Interference In support of the primary hypothesis, pain severity was significantly different between groups, with the NP group reporting greater pain severity than the MSK group. Levels of pain interference did not significantly differ between groups. However, a small to medium effect size was found whereby the NP group also had greater pain interference. Post hoc sample size calculations indicate that a sample size of 65 (per group) would have been necessary to detect a significant difference between groups. However, clinically meaningful differences between groups in both pain severity and pain interference were found. These findings align with previous research that reported greater pain intensity and more pain interference in people with SCI who have NP compared with those who have nociceptive (MSK) pain (Canori et al., 2024). Other research comparing pain severity and/or interference levels in people with NP versus MSK 41 pain and SCI is limited; however, our findings align with previous findings from a longitudinal study that reported greater severity of NP compared to MSK pain in SCI (Siddall et al., 2003). The following sections apply the Biopsychosocial Model (Gatchel et al., 2007) to explain why pain intensity and interference may be greater in those with NP than MSK pain. Each aspect of the biopsychosocial model will be addressed separately. However, it is acknowledged that no aspect of health (biological, psychological, or social) occurs in isolation of the others. 6.2.1 Biological mechanisms affecting pain severity Biological mechanisms affecting pain severity are especially relevant to people with SCI as there is often damage to the central (the brain and spinal cord) and/or peripheral (nerves and sensory and motor receptors) nervous system structures following SCI (Clark et al., 2024). Impacts of SCI on the nervous system are complex as they vary depending on injury location and severity (Clark et al., 2024). Damage to the brain can affect the pain experience, especially if pain processing centers of the brain are directly impacted by the injury. In addition, the structure and function of the brain can change as a result of nerve damage and neuropathic pain following SCI (Solstrand Dahlberg et al., 2018). Lastly, the ability to transmit pain signals from the brain through the spinal cord to the peripheral regions of the body can be impacted by SCI (Vierck, 2020). Currently, there is not enough evidence to suggest if these central mechanisms of pain differ between chronic MSK pain and chronic NP in people with SCI. However, research indicates potential peripheral mechanisms that may differ. Therefore, peripheral mechanisms that can be impacted by SCI, including damage and dysfunction of nerve fibers, are the focus of the following section. Differences in the peripheral mechanisms of NP and MSK pain may be key to understanding the difference in severity between pain experiences. NP is considered pain that 42 arises as a result of dysfunction or disease of the somatosensory nervous system (Bryce, Biering-Sørensen, Finnerup, Cardenas, Defrin, Lundeberg, et al., 2012; T. S. Jensen et al., 2011). Damaged nerve fibers, peripheral sensitization, and central sensitization are characteristic of NP (Finnerup et al., 2021). The main role of the nerves of the somatosensory nervous system is to respond to external stimuli and alert the body to potential danger (Koop & Tadi, 2024). When peripheral nerve fibers become damaged, there is an array of effects on the individual including symptoms such as: 1. loss of sensation, 2. hyperalgesia (hypersensitivity to painful stimuli that leads to an extreme pain response) (Purves et al., 2001), and 3. allodynia, (pain resulting from a stimulus that does not normally evoke pain, like light touch) (He & Kim, 2024). Hyperalgesia and allodynia are both part of the phenomenon called peripheral sensitization, where the peripheral nerves become hypersensitized (Gangadharan & Kuner, 2013). For someone who has peripheral sensitization, their sensory nerves are more responsive to stimuli and/or have a reduced threshold of stimulus they can withstand before sending pain signals to the brain (Gangadharan & Kuner, 2013). In a recent publication, C-fiber damage has been linked to the peripheral components of neuropathic pain (Arcilla & Tadi, 2024). C-fibers are “slow” nerve fibers, known for their large receptive fields that are responsible for relaying pain intensity (Kendroud et al., 2024). Activation of C-fibers results in diffuse, aching, and burning pain (Arcilla & Tadi, 2024). After nerve injury, it has been reported that only 1/3rd of C-fibers are capable of re-generating to reach the skin, leaving the remaining nerves damaged (Arcilla & Tadi, 2024). For this reason, it has been suggested that C-fibers may be responsible for the peripheral components of neuropathic pain (Arcilla & Tadi, 2024). This is an interesting suggestion, as C-fibers have large receptive fields that are responsible for producing poorly localized, burning type pain (Kendroud et al., 2024), which aligns with the most frequently 43 reported characteristic of chronic NP in SCI (i.e., widespread, burning pain) (Majedi et al., 2018). Furthermore, as C-fibers are known for relaying pain intensity (Kendroud et al., 2024), greater C-fiber damage/dysfunction could be a potential explanation for the greater pain severity scores in the NP group. There is another type of nerve fiber responsible for conducting pain signals that could be relevant in NP conditions. A-delta fibers have small receptive fields, fast conduction speed, and the ability to produce sharp, pricking pain (Dafny, 2020; Kendroud et al., 2024). These functions align with the “tingling” and “electric shock-like” symptomology of NP. However, more research should be conducted to identify whether tingling and electric shock-like NP symptoms could be attributed to damage of the A-delta fibers. In comparison, nerve damage is not a primary cause of chronic MSK pain. MSK pain is commonly caused by injury, degenerative diseases, and neuroinflammation affecting tissues of the MSK system (El-Tallawy et al., 2021). MSK pain is localized to specific tissues of the MSK system including muscles, joints, tendons, ligaments and bones (El-Tallawy et al., 2021) making its affected regions easier to pinpoint than NP pain regions. These areas are also supplied with nerve fibers, including C-fibers and A-deltas (Puntillo et al., 2021); however, their functions are different within the MSK system. Normally, in these regions, C-fibers and A-delta (sensory) fibers are silent (Puntillo et al., 2021). They can be triggered by high intensity stimulus, such as stimuli that occur with MSK injury (Puntillo et al., 2021). For example, after bone fracture, inflammation triggers some of these silent fibers to become active and to start to respond to mechanical stimuli that they used to be silent to (Puntillo et al., 2021). Once triggered, they cause the sharp pain characteristic of MSK injury, which is due to activation of the A-delta fibers (the fibers with small receptive fields and fast pain conduction processes; (Oostinga et al., 2020). 44 Over time, the pain evolves into a dull, aching pain which is caused by the activation of C-fibers (the fibers with large receptive fields and slow conduction processes) (Oostinga et al., 2020; Puntillo et al., 2021). In chronic MSK conditions, it is thought that the increased C-fiber activity in bones and joints contributes significantly to the pathological state (Puntillo et al., 2021). Presence of nerve damage and the mechanisms of peripheral sensitization are factors that vary between NP and MSK pain and affect pain severity and could explain greater pain severity for those with NP. It should be noted that there are two other important physiological factors that are involved in both chronic MSK and NP pain conditions: 1. central sensitization, where the neurons in the spinal cord change as a response to prolonged pain signalling and become overactive (Latremoliere & Woolf, 2009), and 2. maladaptive descending inhibitory control processes, where there is a reduction in pain inhibitory signalling coming from the brain after prolonged pain exposure (Ossipov et al., 2014). It is possible that central processes differ between the two pain types in people with SCI. However, there is not enough evidence currently available to support this idea, therefore this section focused on peripheral mechanisms. As such, the interaction between central mechanisms of pain (in both MSK pain and NP) and spinal cord injury should be further explored. In summary, damage of C-fiber nerves leads to dysfunction of the somatosensory nervous system and results in peripheral sensitization in chronic NP conditions. After identifying several shared characteristics between pathological C-fiber activity and NP symptomology (nerve damage causing dysfunction, and poor receptor localization causing widespread, burning pain) we suggest that C-fiber damage following SCI may be a potential explanation for the difference in pain severity found between those with chronic NP and chronic MSK and SCI found in this 45 study. Furthermore, we suggest this could be an area worthy of investigation for researchers and clinicians interested in identifying mechanistic targets for NP treatment. 6.2.2 Psychological mechanisms affecting pain severity The pain experience becomes even more complex when the interplay of psychological and social interactions is considered. A new type of pain was recently described, called nociplastic pain, which is considered pain with symptoms much more severe than would be expected due to the observed level of tissue (MSK) or nerve damage (NP) (Fitzcharles et al., 2021). In the case of nociplastic pain, severity of physical and psychological symptoms-- including pain, mood, memory, and sleep disruption--cannot be explained by underlying biological mechanisms (Fitzcharles et al., 2021). The identification of a pain type that cannot be explained by biological mechanisms provides a basis for considering psychological mechanisms that affect the pain experience. A person’s pain response is highly susceptible to psychological factors, including top-down input from the brain such as beliefs, perceptions, and thoughts about pain (Linton & Shaw, 2011). Negative affective psychological factors, for example, feelings of negativity, sadness, guilt, fear, anxiety, and stress are known to aggravate pain (Janssen, 2002; Linton & Shaw, 2011). In the current study, there tended to be greater negative affect (in the form of stress) in the NP group as well as greater pain severity. This finding points towards a psychological interaction between negative psychological states and pain severity. Between-groups differences in negative affect, and their potential causes, will be discussed further in Section 7.2.2. As further evidence of the importance of psychological mechanisms, psychological interventions show effectiveness at improving chronic pain regardless of pain condition (Driscoll et al., 2021). These findings indicate that: 1. psychological intervention can provide pain relief 46 for those suffering from chronic pain, and 2. finding the root cause of the pain may not be necessary before starting a psychological intervention. Therefore, psychological interventions could provide relief while chronic pain patients wait on waitlists seeking medical help. In summary, between group differences in psychological factors, such as beliefs and perceptions about pain, as well as negative affect (e.g., fear, anxiety, stress) could provide a potential explanation for the greater levels of pain severity reported amongst the chronic NP group. Exploring between group differences further, has important implications for helping to develop specific psychological interventions for those with chronic NP and MSK pain and SCI. 6.2.3 Social mechanisms affecting pain severity Social factors also play a role in the pain experience. They include social environment, level of social support, social interactions, and intrapersonal relationships (Meints & Edwards, 2018). Positive social factors, such as a positive work or home environment, adequate social support, and healthy intrapersonal relationships are known to be beneficial for reducing pain and improving physical functioning in those with pain and disability, including in studies involving individuals with SCI and chronic pain (Meints & Edwards, 2018). Differences in social isolation may provide explanation for the differences in pain severity reported between groups in this study. Past research indicates that those with chronic pain are more susceptible to social isolation, and that improvements in social isolation can directly improve individuals’ emotional and physical functioning (Bannon et al., 2021). There have been no studies comparing social isolation between those with different types of chronic pain and SCI; however, when research on NP and MSK pain is compared, those with NP appear to be at greater risk of social isolation than those with MSK pain. 47 Firstly, those with NP and SCI feel extremely socially isolated (Sparkes & Smith, 2008). In a qualitative study involving men with SCI and NP, participants reported having difficulty articulating their pain experience with others and hiding their pain from people around them. Participants described their experience with NP as a lonely, frustrating time due to difficulty finding the words to explain how NP felt, and socio-cultural pressures to appear masculine and “tough” (Sparkes & Smith, 2008). As evidence of social isolation, one participant said “There was no way to share the pain I was in, it felt there was no way out of this prison I was locked in, and I was very isolated because of all that” due to the inability to understand and describe his pain in a way he could communicate with others (Sparkes & Smith, 2008). Another individual said “I didn’t want to appear a wimp, so I kept it to myself” speaking to the socio-cultural factors at play that may make men even more susceptible to social isolation stemming from NP due to the resistance to sharing intimate details about just how bad it really was (Sparkes & Smith, 2008). As a result of NP, it appears those with NP and SCI can experience extremely isolating emotions and behaviour (Sparkes & Smith, 2008). The biopsychosocial model of pain identifies social isolation as a mechanism that can increase perceived pain (Gatchel et al., 2007). Therefore, extreme social isolation in those with NP and SCI may provide an explanation for the greater levels of pain severity experienced in this group compared to those with MSK pain and SCI. In comparison, those with MSK pain and SCI are also susceptible to loneliness. However, in a recent study, they were no more likely to be socially isolated than those with SCI without chronic MSK pain (T. O. Smith et al., 2019). Together, the results of these studies suggest that people with SCI and NP experience social isolation, which could play a role in the greater pain severity of this condition in comparison to those with SCI and chronic MSK pain. 48 6.2.4 Mechanisms affecting pain interference Given the biological, psychological, and social factors that influence pain, and the possibility that they are experienced more severely in people with NP than MSK pain (see sections 7.1.1, 7.1.2, 7.1.3 above), those with NP may also be more susceptible to pain interference than those with MSK. Those with NP report not being able to escape their pain (Sparkes & Smith, 2008), due to the spontaneous and uncontrollable nature of NP (Costigan et al., 2009). Pain interference is a direct measure of how much pain interferes with day-to-day activities. Therefore, it makes sense that the NP group would experience greater pain interference than the MSK group. Previous research supports that there is greater pain interference in those with NP and SCI compared to those with MSK pain and SCI (Canori et al., 2024). Based on the effect size findings of the current study, pain interference was greater in those with NP than those with chronic MSK (small to medium effect). There are known differences in symptomology associated with chronic NP and chronic MSK pain (Bryce, Biering-Sørensen, Finnerup, Cardenas, Defrin, Lundeberg, et al., 2012), which may explain differences in pain interference. Differences between NP and MSK include: 1. The spontaneous nature of NP attacks, and 2. less ability to control NP attacks. Firstly, there are known triggers of chronic MSK pain, such as beginning movement, over-activity, and time of day (more prevalent at the end of the day) (El-Tallawy et al., 2021). In contrast, NP is known for being spontaneous, intermittent, and attacking the individual sporadically throughout the day (Costigan et al., 2009; Sparkes & Smith, 2008). Secondly, those with chronic MSK pain may receive relief from common treatments, including physical and pharmaceutical intervention (Babatunde et al., 2017; Fullen et al., 2023). In comparison, current 49 treatments for NP have severe adverse effects and are only moderately effective, resulting in inadequate treatment for most people with NP (Hange et al., 2022). As a result, those with NP face extreme challenges managing their symptoms which create difficulty with daily activities, work, social activities, sleep disturbances, and emotional distress (Szewczyk et al., 2022). For these reasons, chronic NP may be more disruptive in nature and more difficult to manage than chronic MSK pain, which could provide an explanation for the greater levels of pain interference in this group compared to those with chronic MSK. 6.3 Subjective well-being Well-being related findings were unsupportive of our secondary hypothesis, as there were no statistically significant differences in aspects of SWB (life satisfaction, unpleasant affect, pleasant affect) found between groups. However, NP tended to score higher than MSK on perceived stress (medium effect) and lower on life satisfaction (small to medium effect). These findings are supported by previous research reporting that those with NP have lower subjective quality of life than those with nociceptive (MSK) pain (Canori et al., 2024). However, findings for positive affect trended in the opposite direction as hypothesized, indicating higher positive affect in those with NP than those with MSK (small effect). Findings will be discussed separately for the three aspects of SWB. 6.3.1 Life satisfaction Life satisfaction was measured using the Satisfaction with Life Scale. Results from the ANOVA were unsupportive of the secondary hypothesis that the chronic NP group would have lower life satisfaction than those with chronic MSK. Post hoc sample size calculations indicate that a sample size of 57 (per group) would have been necessary to detect a significant difference between groups. However, there was a small to medium effect in the hypothesized direction. 50 Canori and colleagues compared SWB between groups and reported lower SWB scores in those with NP, although life satisfaction specifically was not compared between groups (Canori et al., 2024). As such, were unable to identify any previous research comparing levels of life satisfaction in individuals with SCI and different chronic pain types. More generally, these findings are supported by research that suggests experiencing chronic pain is associated with lower life satisfaction than experiencing no pain (Budh & Österåker, 2007). Furthermore, a correlation between life satisfaction and pain has been widely demonstrated, whereby improvements in pain can lead to improvements in life satisfaction and vice versa (Williams et al., 2024). The findings from the current study support the idea that pain and life satisfaction go together, as the group with higher pain severity (NP group) also showed relatively lower levels of life satisfaction. Although our results did not indicate significant differences between groups, effect sizes are an indication that further research should be done with a larger sample size to investigate potential differences in life satisfaction between those with chronic NP and chronic MSK pain and SCI. Ultimately, if a difference exists between groups, efforts to improve life satisfaction may be a worthwhile avenue to explore in the development of future interventions for those with SCI and chronic NP. 6.3.2 Negative affect Stress is an example of negative affect and was measured using the Perceived Stress Scale. ANOVA findings were unsupportive of the secondary hypothesis that there would be greater stress in the chronic NP group. However, effect size calculations showed tendency for those in the NP group had greater stress (medium effect) than those in the MSK group. Post hoc sample size calculations indicate that a sample size of 37 (per group) would have been necessary to detect a significant difference between groups. We were unable to identify any studies that 51 compared stress between those with chronic NP and chronic MSK pain. Despite this challenge, results are supported by previous research that suggests those with SCI and NP experience greater levels of other types of negative affect, including depression and pain catastrophizing, compared with those who have SCI and MSK (Canori et al., 2024). Furthermore, the interplay between pain and stress is well documented, including the suggestion of mechanisms of pain modulation whereby negative affect leads to magnification of chronic pain and results in pain sensitivity (Janssen, 2002). This relationship can be bi-directional, as pain can also be a source of stress among individuals with chronic pain (Mickle et al., 2020). In people with SCI, reductions in pain and stress have been suggested as potential mediators for improvements in subjective well-being in exercise interventions (Martin Ginis et al., 2003). Furthermore, the role of stress in the pain experience has been depicted in the biopsychosocial model of pain (Gatchel et al., 2007) and the usefulness of considering stress in pain treatment has been highlighted by current psychological pain theories (Meints & Edwards, 2018). Since the primary findings of this study suggest that those with chronic NP and SCI experience significantly more pain than those with chronic MSK pain (Section 7.1), we suggest this group is also susceptible to greater stress. This is supported by our secondary findings, as effect size findings indicate that those with chronic NP tend to experience greater stress than those with chronic MSK. Ultimately, research should be conducted with a larger sample size to determine if there are significant differences in stress levels between the two pain groups and explore potential implications of high stress for those with SCI and chronic pain. 6.3.3 Positive affect As previously stated, results were unsupportive of our secondary hypothesis as there was no significant difference in positive affect between groups. However, effect size calculations for 52 pleasant affect suggest a small, but meaningful difference between groups, although it was in the opposite direction as hypothesized. Post hoc sample size calculations indicate that a sample size of 123 or greater (per group) would have been necessary to detect a significant difference between groups. In the current study, results demonstrated that the NP group had greater positive affect (small effect) than the MSK group. These findings are not supported by any previous research as this is the first study to compare positive affect between people with chronic NP and chronic MSK pain and SCI. Interestingly, research conducted in athletes with SCI and NP demonstrated similar findings, where the group with greater pain severity also had greater positive affect than the comparison group (Todd et al., 2023). In the following sections, potential explanations will be provided for why the direction of the observed findings are opposite to what were hypothesized. In general, there is a negative correlation between positive affect and pain severity, where positive affect can attenuate pain experiences in clinical and healthy populations by reducing pain (Hanssen et al., 2017; Ong et al., 2020). Considering this relationship and given those with NP experience greater levels of pain (Section 5.3), we expected to observe lower levels of positive affect in the NP group. However, effect sizes indicate that those with chronic NP and SCI report greater positive affect (small effect) than those with chronic MSK. Todd et al. found that paralympic athletes with SCI and NP experienced greater pain severity but greater positive affect compared to recreational athletes with SCI and NP (Todd et al., 2023). Todd et al’s findings coupled with the present thesis findings prompt the question: what is unique about people with SCI and NP that could explain why they report greater positive affect than a SCI group that reports less pain? To try to answer this question, I spoke with a person with lived experience of SCI and NP and conducted a post-hoc analysis of additional data 53 within the larger EPIC-SCI data set. Based on these other sources of knowledge, I propose that people with chronic NP and SCI may rely on positive affective behaviours as a way of coping with NP. 6.3.4 Positive affect as a coping mechanism for those with SCI and NP Positive affect is described as momentary feelings of pleasure, including happiness, joy, contentment, and pride (Diener et al., 1999). Positive affect is known to have beneficial psychological effects, such as increasing well-being and reducing pain (Fredrickson, 2001; Ong et al., 2020). Aspects of positive affect are highly involved in pain coping strategies. For example, the Coping Strategies Questionnaire (CSQ) is a questionnaire aimed at assessing pain-related beliefs and coping strategies (Monticone et al., 2014). The CSQ asks individuals how often they use certain coping strategies like distraction, positive self-statements, and praying to cope with their pain. Specifically, coping strategies include things like thinking of things they enjoy, thinking of something other than pain, praying, replaying pleasant experiences in their mind, and more. Many of these coping strategies induce positive affective states (happiness, joy, pride, hope) in users. For instance, “I replay in my mind pleasant experiences” (CSQ Item 8) and “I think of things I enjoy” (CSQ Item 1) are examples of coping strategies that induce a positive affective state (i.e., happiness) (M. M. Smith et al., 2016). After reviewing research on pain coping and positive affect, I decided that accessing information about participants’ pain coping strategies could provide valuable insight into interpretation of the positive affect results. The 7-Item CSQ was included in the larger EPIC-SCI trial. Data were available for 30 participants in the NP group and 11 in the MSK group. As such, I conducted a post-hoc analysis to determine if a difference in pain coping could help explain the effect size in positive affect found in this study. Interestingly, those with chronic NP used significantly more pain coping 54 strategies (19.61 + 6.1) than those with chronic MSK pain (11.00 +3.07; p<0.001, large effect size—Cohen’s d= 1.78). These findings support the idea that people with NP are using more positive affective coping strategies, which in turn could lead to more positive affect. Differences in coping between groups could be explained by the difficulty of adapting to and managing NP compared to MSK pain. First, likely everyone has had or will have some form of MSK pain during the course of their lives (El-Tallawy et al., 2021), such as an acute injury, and are familiar with the experiences (e.g., feelings, implications) associated with MSK pain. In contrast, most individuals are not exposed to NP to the same extent. For those with NP resulting after SCI, the NP is typically an entirely new challenge. For example, the prevalence of NP in the general population is 7-10%, whereas the prevalence of NP in those with complete and incomplete SCI is 74% and 67%, respectively (Baskozos et al., 2023; Kim et al., 2020a). A newly injured person not only has to adapt to lifestyle changes associated with SCI, but they are also burdened by uncontrollable pain. In summary, people with NP may have to work harder to cope with pain, resulting in greater use of pain coping strategies on the CSQ than those with MSK. Secondly, there are several commonly available treatments that are effective at providing short-term MSK pain relief, including acetaminophen (Tylenol), non-steroidal anti-inflammatory drugs (NSAIDS) (e.g., aspirin), corticosteroid injection, and physical therapy (Babatunde et al., 2017; Fullen et al., 2023) (Section 7.1.4). In contrast, current treatments available for NP have harsh side effects for moderate efficacy (Hange et al., 2022). As a result, most people with NP receive inadequate and incomplete treatment (Hange et al., 2022). People with chronic NP and SCI report feeling helpless, and report the pain experience is “unescapable” as they are unable to find relief (Sparkes & Smith, 2008). When people become desperate for pain relief, they are 55 more likely to seek alternative treatments, including psychological intervention (Farley et al., 2023). As evidence of this, it has been reported that those who seek psychological intervention are those who suffer from greater pain intensity and lower quality of life (Farley et al., 2023). Furthermore, the authors reported that those who sought psychological intervention had already applied many more coping strategies than those who had not sought psychological intervention. Therefore, we suggest that those with SCI and chronic NP are more likely to be trying to cope with their pain through positive affective behaviours, such as thinking happy thoughts, compared to those with chronic MSK pain. Their greater reliance on psychological intervention, including practicing more positive affect as a last resort for pain relief could explain the greater levels of pain coping and positive affect found among this group. 6.4 Leisure Time Physical Activity LTPA was not significantly different between groups, which is unsupportive of the tertiary hypothesis, that those in the MSK group would have greater levels of LTPA. Interestingly, differences were in the opposite direction of the predicted findings, suggesting those with NP participate in more minutes of total LTPA per week than those with MSK pain. Post hoc sample size calculations indicate that a sample size of 62 (per group) would have been necessary to detect a significant difference between groups. The NP group also did more minutes of mild and moderate intensity LTPA per week (small to medium effect) but the MSK group reported more heavy intensity LTPA. The finding for moderate intensity LTPA in those with NP is supported by previous research that demonstrated more minutes of moderate-vigorous physical activity per week in those with NP and SCI compared to those with MSK and SCI (Canori et al., 2024). Unfortunately, Canori et al. did not separate intensities of MVPA into moderate and vigorous, 56 therefore we do not know if differences in time spent on the two LTPA intensities followed the same pattern as our findings. Also, Canori et al. did not discuss potential explanations for differences in LTPA. In the following sections, we will discuss potential explanations drawing on both scientific research and anecdotal evidence/lived experience. We suggest that greater levels of LTPA in those with NP may be explained by the different immediate effects of exercise on individuals with varying pain types. Furthermore, there may be psychological factors (i.e., motivation, fear avoidance) at play that motivate and deter each group from specific exercise intensities. Firstly, exercise may increase NP but not MSK pain. Movement has a tendency to aggravate MSK pain at the beginning, provide relief during, and can result in discomfort and soreness after, if the affected MSK tissue is overused (El-Tallawy et al., 2021). Many individuals with SCI are limited to upper extremity exercises due to physical impairment of the lower body. Wheelchair dependent users are also reliant on their upper extremities for daily ambulation in their chairs. On one hand, the reliance on upper extremity movement for exercise and daily activity puts individuals with chronic MSK pain (pain of the shoulders, arms, wrists, back, neck, etc) at high risk of overuse injury (Liampas et al., 2021). On the other hand, moderate intensity exercise can alleviate NP during and immediately after a training session (Leitzelar & Koltyn, 2021; Todd, Van Der Scheer, et al., 2021; Todd & Martin Ginis, 2018). Considering NP is alleviated by exercise, those with NP are less likely to aggravate their pain problem by being physically active than those with MSK pain. For these reasons, it is likely that those with NP are more motivated to participate in activity as they reap immediate benefits. Likewise, those with MSK may be more avoidant of exercise due to the immediate discomfort that they experience as they begin activity, and the risk of overuse injury afterward. 57 Secondly, the influences of motivation and fear-avoidance on physical activity are well studied phenomenon and can be explained by the COM-B Model for Behaviour Change (Capability-Opportunity-Motivation) and the Fear-Avoidance Model (Michie et al., 2011; Vlaeyen & Linton, 2000). The COM-B model describes that if an individual is capable, has the opportunity, and the motivation to do a behaviour, it is more likely they will perform the behaviour. In this case, for people in the NP group, experiencing pain relief when exercising may increase their motivation to exercise. In contrast, when people experience pain, negative thoughts can lead to fear of movement, causing them to develop avoidance to the pain-inducing behaviour. This phenomenon is described by the Fear-Avoidance Model and is known to occur in people with chronic musculoskeletal pain (Vlaeyen & Linton, 2000). People in the MSK pain group may be avoiding physical activity due to the fear of aggravating of their pain and/or experiencing overuse injury. Furthermore, we suggest considerations should be made when measuring and recommending exercise in those with SCI and chronic pain, as exercise intensities may have differential effects on chronic pain. Our data suggest that both groups are more likely to do moderate LTPA than heavy intensity LTPA. This is supported by previous research that reports more activity being done by people with SCI of a moderate than vigorous intensity (Martin Ginis, Arbour-Nicitopoulos, et al., 2010). As described in the previous section, overuse can cause injury to MSK tissue. Therefore, those with MSK could be less likely to participate in heavy intensity LTPA. Interestingly, heavy intensity LTPA may have a similar effect on those with NP as those with MSK. High intensity exercise increases the level of cortisol (stress hormone) in the bloodstream, which heightens the sympathetic nervous system and results in increased physical stress (Hill et al., 2008). Since NP is caused by disease or dysfunction of the 58 nervous system, increasing the sympathetic response in individuals with NP may not be beneficial for this reason. Research has reported stress as a known aggravator of NP (Li et al., 2017). Therefore, it is possible heavy intensity activity may be less enjoyable for individuals with NP, as it heightens the stress response (Hill et al., 2008). It should also be noted that depending on injury severity and access to accessible exercise equipment and opportunities, it may be difficult for individuals with SCI to reach heavy intensity activity. Therefore, individual capability and opportunity could also be a factor explaining fewer minutes of heavy intensity LTPA than mild and moderate intensity LTPA in both of these groups. In summary, researchers and clinicians should be cautious of exercise intensity while measuring or recommending exercise for those with SCI and chronic pain, as literature suggests that higher intensity activity may aggravate chronic pain in SCI, regardless of pain type. In conclusion, we suggest that greater levels of LTPA in those with NP (small to medium effect) found in this study can be explained by the different immediate effects of exercise on pain types and the psychological factors that contribute to their motivation (or avoidance) to participate in physical activity. Furthermore, distinguishing intensities of physical activity may be an important consideration for measuring or recommending physical activity in populations with SCI and chronic pain. 6.5 Strengths and Limitations The following section will outline strengths and limitations of this study. 6.5.1 Sample size First, we did not have equal numbers of participants in each group. This study used a cross-sectional design with natural groupings, whereby groups were created based on pain type, after data was collected. As a result, final sample sizes were n=34 (NP group) and n=12 (MSK 59 group). Having unequal sample sizes is disadvantageous for statistical power. In this study, ANOVAs were used to test primary, secondary, and tertiary hypotheses. Generally, having unequal sample sizes between comparison groups introduces lower statistical power in ANOVAs as statistical power is based on the smallest sample size (Bhandari, 2023). Lower power is less desirable as it means there is a smaller chance of detecting an effect (Bhandari, 2023). This is a study limitation as several comparisons had small and small-medium effect sizes (hypothesis 2 & 3) but did not reach statistical significance. Post hoc sample size calculations indicated that sample sizes ranging from 37 to 123 (per group) would have been necessary to detect a significant difference in the SWB and LTPA variables. Alternatively, the unequal sample sizes represent a strength of this study. Literature reports higher prevalence of NP compared to MSK pain in individuals with SCI (Hunt et al., 2021). Therefore, using a natural grouping approach tells us about how many individuals in a sample of the population with SCI have each type of pain as their worst pain problem. In our sample of 46 participants, 73.9% (n= 34) had primary NP and 26.1% (n=12) had primary MSK pain. This is on par with other studies, as Kim et al found that 69.1% of people with SCI reported NP among their sample of 253, and Canori et al showed 70% of people with SCI reported primary NP among their sample of 17 (Canori et al., 2024; Kim et al., 2020b). Similar to our findings, Canori et al showed a lower prevalence of primary MSK compared to primary NP, with 41% of individuals reporting primary MSK. These similarities speak to the representativeness of our sample. In contrast, had we purposefully recruited the same number of people for each group, we would not have gained insight into the prevalence of chronic pain types among people with SCI and chronic pain who live in BC. Furthermore, although the sample was not large enough to detect significance for two hypotheses, the achieved sample size of 46 participants 60 should be considered an accomplishment. To date, this is the largest study to compare levels of pain, SWB, and LTPA between people with SCI and chronic NP and MSK pain. 6.5.2 Restricted physical activity levels Second, inclusion criteria for the larger EPIC-SCI trial purposefully selected individuals not currently reaching the SCI exercise guidelines. This is a limitation as analyses compared PA levels among those who are relatively inactive. As such, this study lacks insight from those with SCI and chronic pain who are currently meeting the SCI physical activity guidelines. The inclusion of low active people was purposeful as it strengthens other aspects of the EPIC-SCI study design. First, for the larger trial, we can assess the effects of increasing PA participation among participants who are currently at the lower end of the PA scale. Second, sampling individuals who do not meet the SCI exercise guidelines is representative of the population of those with chronic SCI. A population-based study of 695 people with SCI reported that 50% do not do any physical activity (Martin Ginis, Latimer, et al., 2010). Furthermore, as pain presents additional barriers to being physically active (Connolly et al., 2024), those with chronic pain and SCI may be even less physically active. Thus, an inactive sample may contribute to the representativeness of findings. 6.5.3 Complexity of pain problems Third, as many individuals with SCI experience more than one pain problem, categorization of pain type is a complex process. Complexity of pain presentation is a limitation of this study as many individuals reported both NP and MSK pain. By recommendation of our colleagues (Canori et al., 2024), we categorized pain type based on the primary pain (worst pain) reported. This resulted in 34 individuals with primary NP and 12 individuals with primary MSK. However, when secondary and tertiary pain problems are considered, 16 individuals only had 61 NP, 4 individuals only had MSK, and 26 individuals had both types of pain (primary NP with secondary or tertiary MSK =17, and primary MSK with secondary or tertiary NP=9). This poses a limitation to the study as comparison groups are not specific to participants who only experienced one type of pain. As such, it is not possible to say pain and SWB results of each pain group (NP or MSK) are specific to that only those who have that type of pain. However, if we were to limit inclusion to only those with one pain problem, sample sizes would have not been enough (n=17 [NP], n= 4 [MSK]) to make meaningful comparisons or draw any conclusions. In addition, the complexity of participants’ pain presentation is representative of the real-world experience of the population with chronic pain and SCI, who are often affected by more than one pain type (Mahnig et al., 2016). The ability to categorize based on primary pain type despite the difficulty and complexity of pain presentation is a very big accomplishment and strength of this study. Furthermore, despite this challenge, we were still able to identify significant differences in pain severity between groups based on primary pain problems. In summary, conducting research in individuals with SCI and chronic pain is challenging due to the complexity of classifying pain phenotypes. This challenge introduces limitations to the study, such as 1) unequal sample sizes of NP and MSK groups, and 2) individuals presenting with multiple pain problems. In addition, sampling individuals at the lower end of the PA scale limits us to drawing conclusions about people with SCI who may be more physically active. However, research suggests that: 1) unequal distributions of those with NP and MSK, 2) individuals experiencing multiple pain problems, and 3) individuals experiencing low levels of physical activity, are all common in this population. Therefore, we propose that these challenges also pose strengths to the study, increasing the representativeness of our findings to the population of those with SCI and chronic pain. 62 Chapter 7. Conclusion 7.1 Contributions, Implications, and Future Directions This study contributes to the minimal literature examining differences in biopsychosocial factors that affect chronic pain in individuals with SCI. Firstly, this is the largest study to collect and compare levels of pain, well-being, and physical activity between individuals with different types of chronic pain and SCI. In addition, to our knowledge, this is only the second study to measure these outcomes (cf. Canori et al) and the first study to discuss or interpret between- groups differences in these variables, as a function of pain type. Thirdly, this is the first study to compare life satisfaction and affective states (positive and negative) between those with different types of chronic pain and SCI. This study has important implications for scientists and clinicians. From a scientific standpoint, this study provides direction and impetus for scientists to study biopsychosocial factors associated with different pain types, as we have demonstrated that there are meaningful differences across the two pain groups. In addition to the specific research directions presented in the preceding paragraphs, in general, future research should look at mechanisms that might account for these and other differences. From a clinical standpoint, the results suggest people with SCI and chronic NP experience worse outcomes (greater pain, greater stress, and lower life satisfaction) and therefore may require more support from clinicians than those with MSK pain. It is important to start providing additional support for people experiencing chronic NP as research is unlikely to impact their lives for many years. Future research should look at targeting multiple components of the biopsychosocial model of pain to improve outcomes in those with SCI and chronic pain; with emphasis on treating chronic NP. Specifically, improving pain, stress, and life satisfaction 63 in those with chronic NP, as they tend to experience worse outcomes and have greater difficulty managing their pain. 7.2 Conclusion The purpose of this study was to describe and compare pain, well-being, and LTPA between people with SCI who have chronic NP versus chronic MSK pain. Findings indicate that those with NP have significantly greater pain, greater levels of pain interference (small to medium effect size), greater negative affect (i.e., stress; medium effect size), and lower life satisfaction (small to medium effect size). Perhaps the most interesting finding is that despite worse pain severity, stress, and life satisfaction, the NP group tended to have more positive affect (small effect size) and did more LTPA (small to medium effect) than those with MSK pain. Additionally, post hoc analyses indicated that those with NP also have significantly greater levels of pain coping. Taken together, results suggest there are meaningful differences in pain, well-being, and physical activity between individuals with SCI chronic NP versus chronic MSK that may be explained by different mechanisms associated with the two pain phenotypes. 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Therapeutic Recreation Journal. https://doi.org/10.18666/TRJ-2023-V57-I2-11760 85 APPENDICES Appendix A: Study Materials Demographic Form International Spinal Cord Injury Basic Pain Dataset v2.0 SF-36 Vitality (Fatigue) Subjective Well-Being Measures: 1. Perceived Stress Scale 2. SCI-QOL measures of Positive Affect and Well-being 3. Diener’s Satisfaction with Life Scale Modified LTPAQ-SCI to capture exercise guideline activity DN4 86 87 88 89 90 91 92 93 94 95 96 DN4 – QUESTIONNAIRE To estimate the probability of neuropathic pain, please answer yes or no for each item of the following four questions. INTERVIEW OF THE PATIENT QUESTION 1: Does the pain have one or more of the following characteristics? YES NO Burning . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ❏ ❏ Painful cold . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ❏ ❏ Electric shocks . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ❏ ❏ QUESTION 2: Is the pain associated with one or more of the following symptoms in the same area? YES NO Tingling . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ❏ ❏ Pins and needles . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ❏ ❏ Numbness . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ❏ ❏ Itching . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ❏ ❏ EXAMINATION OF THE PATIENT 97 YES = 1 point NO = 0 points QUESTION 3: Is the pain located in an area where the physical examination may reveal one or more of the following characteristics? YES NO Hypoesthesia to touch . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ❏ ❏ Hypoesthesia to pinprick . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ❏ ❏ QUESTION 4: In the painful area, can the pain be caused or increased by: YES NO Brushing? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ❏ ❏ Patient’s Score: /10 98 The 7-Item Pain Coping Strategies Questionnaire Adapted from the 14-Item Pain Coping Strategies Questionnaire, available from: https://www.phenxtoolkit.org/protocols/view/860301#:~:text=The%20Coping%20Strategies%20Questionnaire%20(CSQ,representing%20%22Always%20Do%20That%22 99 Appendix B. Testing assumptions of ANOVA for transformed variables. Group n Skewness Kurtosis Shapiro-Wilks Levene’s Test SQRT (Pain Severity) NP 33 -0.055 -1.456 0.002 0.526 MSK 11 -0.548 1.998 0.285 Log10 (Perceived Stress Scale) NP 33 -0.161 0.820 0.316 0.715 MSK 12 -1.633 4.181 0.025 Log10 (Positive Affect and Well Being) NP 33 -0.701 -0.635 0.150* 0.995 MSK 12 -2.552 7.199* <0.001 Log10 (LTPA mild) NP 34 -0.451 -1.275 <0.001 0.805 MSK 11 -0.188 -1.792 0.029 Log10 (LTPA moderate) NP 34 -0.283 -1.556 <0.001 0.683 MSK 12 -0.466 -1.746 0.012 Log10 (LTPA heavy) NP 34 1.897 1.890 <0.001 0.033 MSK 12 0.834 -1.569 <0.001 Log10 (LTPA mod + heavy) NP 34 -0.011 -1.807 <0.001 0.319 MSK 12 -0.330 -1.742 0.022 Log10 (LTPA all) NP 34 -0.306 -1.654 <0.001 0.134 MSK 12 -0.879 -0.917 0.010 100 Note: SQRT= square-root, Log10= logarithm, NP= neuropathic pain, MSK= musculoskeletal pain.
Thesis/Dissertation
eng
Health and Exercise Sciences
Vancouver : University of British Columbia Library
Attribution-NonCommercial-NoDerivatives 4.0 International
Graduate
Martin Ginis, Kathleen A. (Kathleen Anne), 1968-
Pain, well-being, and physical activity in adults with chronic pain and spinal cord injury
Text