Following unilateral spinal contusion pregabalin has an at‐time effect on pruritus and a protective effect on mechanosensory nociception, but does not improve ipsilateral motor outcomes with early administration in rats

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. Using a rat model of unilateral cervical contusion, we 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 for food pellet retrieval (MSA). Additionally, pruritus and noxious mechosensation were assessed through behavioural evidence of scratching and the Randall‐Selitto analgesiometre, respectively. Finally, we used immunohistochemistry to characterize the primary afferent axons responsible for conveying signals related to nociception and itch. We found no significant relationship between the early administration of pregabalin and improved motor scores in the affected forelimb following MSA analysis. However, rats receiving pregabalin had improved performance on the MSA using their contralateral paw, suggesting alleviation of ongoing pain. Additionally, we found that self‐injurious scratching, often displayed by animals with this type of injury, was greatly reduced in those treated with PGB. However, following a two‐month sham injury experiment without PGB treatment, it was found that the scratching was not necessarily due to SCI, except for a small number of cases in which scratching included the territory of the greater auricular nerve. Furthermore, results of the Randall‐Selitto analgesiometre indicate a protective effect that lasted after discontinuation of PGB. Finally, we saw no changes in the density of pruritic and nociceptive primary afferents just rostral to the site of injury. Our findings suggest that in rats with a unilateral SCI, PGB treatment has a possible protective effect on mechanosensory nociception, aids in diminishing pain and itch during use, and contrary to the human cohort study, does not improve motor outcomes with early administration.Support or Funding InformationWings for Life; Natural Sciences and Engineering Research Council (NSERC)This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.