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Peripheral mechanisms of nerve growth factor-induced masticatory muscle sensitization : a model of temporomandibular disorders pain Mann, Mandeep Kaur


It has been speculated that Nerve Growth Factor (NGF), a neurotrophic protein, may play a role in the pathophysiology of temporomandibular disorders (TMD). TMD are characterized by ongoing and activity-related pain in the jaw joint and muscles, and are more prevalent in women than in men. Indeed, intramuscular injection of human NGF into the masseter (jaw closer) muscle of healthy male subjects, though not acutely painful, does cause a prolonged period of activity-related muscle pain reminiscent of TMD symptoms [187]. The present study tested whether this human NGF-induced mechanical sensitization is mediated, in part, through a decrease in the mechanical sensitivity of primary afferent fibers that innervate the masseter muscle. In this randomized, blinded study, the effect of intramuscular injection of rat NGF (2.5 and 25 μg/ml) into non-inflamed masseter muscle on the mechanical threshold (MT) of rat masseter muscle afferent fibers was investigated for 6 hours post-injection. The level of plasma protein extravasation into the masseter muscle was also measured to determine if exogenous rat NGF causes muscle tissue inflammation. The results of the study indicated no treatment or sex differences in evoked afferent discharge, suggesting that administration of rat NGF did not excite afferent fibers in male or female rats. There was also no significant treatment, sex or time effect on the relative MT of masseter muscle afferent fibers. Intramuscular injection of rat NGF did not cause muscle inflammation. Nevertheless, some sex-related differences in the baseline properties of masseter muscle afferent fibers were observed. A significant log-linear relationship was identified between fiber CV and baseline MT for afferent fibers in males but not for fibers in females. There was also a positive correlation between baseline MT and estrogen levels for a subgroup of slow Aδ fibers (2-10 m/s) in females, but not in males. The finding that rat NGF does not evoke significant masseter muscle afferent discharge is consistent with previous results, which indicated injections of human NGF are not painful in human subjects. The failure of intramuscular injection of rat NGF to affect the mechanical sensitivity of masseter muscle afferent fibers suggests that central mechanisms may be more important for human NGF-induced mechanical sensitization.

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