Abstract
Loss of function is usually considered the major consequence of spinal cord injury (SCI). However, chronic pain severely compromises the quality of life of many SCI patients. Recently, microglial cells in enhanced response states have been proposed to contribute to chronic pain following SCI. Here we report that following contusion injury, the microglial cysteine protease cathepsin S (CatS) is critical for the maintenance of SCI-induced neuropathic pain and spinal microglial response. Following SCI, significant mechanical and thermal hypersensitivity developed in both hind-paws. Prolonged intrathecal administration of the CatS inhibitor LHVS (morpholinurea-leucine-homophenylalanine- vinyl sulfone-phenyl), commencing day 26 post-SCI, resulted in significant attenuation of established mechanical and thermal pain behaviours compared to vehicle. This attenuation was evident as early as 24hrs following treatment initiation, and was maintained throughout the 7 day duration of drug administration. In addition, following the 7 day treatment period LHVS significantly attenuated the SCI-induced response of microglial in the lumbar dorsal horn of the spinal cord. We suggest that following SCI, CatS expressed by spinal microglia, is critical for the maintenance of below the level pain induced by contusion injury and suggest that CatS inhibition constitutes a novel therapeutic approach for the treatment of chronic pain associated with SCI.
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call