RESEARCH ARTICLE
Cathepsin S Inhibition Attenuates Neuropathic Pain and Microglial Response Associated with Spinal Cord Injury
Anna K.Clark, Fabien Marchand, Marta D’ Auria, Meirion Davies, John Grist, Marzia Malcangio, Stephen B.McMahon
Article Information
Identifiers and Pagination:
Year: 2010Volume: 3
First Page: 117
Last Page: 122
Publisher ID: TOPAINJ-3-117
DOI: 10.2174/18763863010030400117
Article History:
Received Date: 08/03/2010Revision Received Date: 02/07/2010
Acceptance Date: 05/07/2010
Electronic publication date: 11/10/2010
Collection year: 2010
open-access license: This is an open access article distributed under the terms of the Creative Commons Attribution 4.0 International Public License (CC-BY 4.0), a copy of which is available at: https://creativecommons.org/licenses/by/4.0/legalcode. This license permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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.
