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Skilled reaching deterioration contralateral to cervical hemicontusion in rats is reversed by pregabalin treatment conditional upon its early administration Erskine, Erin

Abstract

Anticonvulsants like pregabalin (PGB) are the first-line treatment for neuropathic pain caused by traumatic injury and non-traumatic diseases of the central nervous system. Recent evidence from a human cohort study suggests that early use of pregabalin after spinal cord injury (SCI) may result in improved motor scores, however, it is unknown to what extent changes in spinal neural circuitry are involved. Backwards translation into a rat model is the first step towards understanding these possible changes. Using a rat model of unilateral cervical contusion, I examined the effect of pregabalin treatment on both motor and sensory function. For four weeks post-injury, rats were given daily pregabalin or filtered water via oral gavage. Motor function was scored using the Montoya staircase assessment (MSA) of fine motor skills. Additionally, pruritus and noxious mechanosensation were assessed through behavioural evidence of scratching and the Randall-Selitto analgesy-meter, respectively. I found no evidence of improved motor scores in the affected forelimb following MSA analysis with the early administration of pregabalin. There was an unexpected deterioration of motor function contralateral to injury, and this was mitigated by early PGB treatment. Additionally, I found that self-injurious scratching, often occurring in animals with this type of injury, was greatly reduced in those treated with PGB. Finally, results of the Randall-Selitto analgesy-meter indicate a protective effect of (PGB) even after its discontinuation. Our findings suggest that in rats with a unilateral SCI, pregabalin treatment has an at-time effect on pruritus and neuropathic pain, a possible protective effect on mechanosensory nociception, and contrary to a human cohort study, does not improve ipsilateral motor outcomes with early administration.

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