Changes in Spinal Cord Following Inflammatory and Neuropathic Pain and the Effectiveness of Resiniferatoxin
Mruvil Abooj, Mahendra Bishnoi*, Christine A. Bosgraaf, Louis S. Premkumar
Identifiers and Pagination:Year: 2016
First Page: 1
Last Page: 14
Publisher Id: TOPAINJ-9-1
Article History:Received Date: 31/3/2015
Revision Received Date: 20/11/2015
Acceptance Date: 24/11/2015
Electronic publication date: 14/3/2016
Collection year: 2016
open-access license: This is an open access article licensed under the terms of the Creative Commons Attribution-Non-Commercial 4.0 International Public License (CC BY-NC 4.0) (https://creativecommons.org/licenses/by-nc/4.0/legalcode), which permits unrestricted, non-commercial use, distribution and reproduction in any medium, provided the work is properly cited.
Peripheral inflammation or nerve injury results in changes in the spinal cord, initiating a process of central sensitization. Although nociceptive Transient Receptor Potential (TRP) channels have been studied extensively, the role of these channels expressed at the central terminals in the spinal cord is not fully understood. Here, we studied the expression and function of TRPV1 channels at the spinal cord following induction of inflammatory pain by Complete Freund's Adjuvant (CFA) and neuropathic pain by Chronic Constriction Injury (CCI). Rats treated with CFA or subjected to CCI developed long-term thermal and mechanical hypersensitivity. Peripheral inflammation or injury induced an inflammatory response at the levels of spinal cord, which included activation of glia and increased levels of proinflammatory mediators. As a result, expression of TRPV1 was significantly increased and the associated function of TRPV1-mediated CGRP release was also significantly increased. Single intrathecal administration of resiniferatoxin (RTX), an ultrapotent TRPV1 agonist, selectively reversed inflammatory thermal hypersensitivity and the associated changes in TRPV1 expression and function without affecting mechanical hypersensitivity. In summary, peripheral nerve activity triggers an inflammatory response at the spinal dorsal horn, which results in enhanced expression and function of TRPV1 channels. Targeting TRPV1 expressed in the central terminals is a viable strategy to alleviate certain modalities of pain.