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Peripheral Calcitonin Gene-Related Peptide Receptor Activation and Mechanical Sensitization of the Joint in Rat Models of Osteoarthritis Pain

Lookup NU author(s): Dr Craig Bullock

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This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License (CC BY-NC 4.0).

Abstract

Objectives. To investigate the role of the sensory neuropeptide calcitonin gene-related peptide (CGRP) in peripheral sensitization in experimental osteoarthritis (OA) pain.Methods. Experimental knee OA was induced in rats by intra-articular monosodium iodoacetate (MIA) or meniscal transection (MNX). Single-unit recordings of joint-innervating nociceptors were obtained in MIA- and saline-treated rats following CGRP, and the CGRP receptor antagonist CGRP_8-37. Effects of CGRP_8-37 were also examined in MNX- and sham-operated rats. Protein and messenger RNA levels of CGRP receptor components in L3-4 dorsal root ganglion (DRG) were investigated following MIA-treatment.Results. In both MIA-treated and MNX-operated rats, the mechanical sensitivity of joint nociceptors was enhanced compared to controls. Exogenous CGRP increased mechanical sensitivity in a greater proportion of joint nociceptors in MIA- than saline-treated rats. Local blockade of endogenous CGRP by CGRP_8-37 reversed both the MIA and MNX-induced enhancement of joint nociceptor responses. Joint afferent cell bodies co-expressed the receptor for CGRP, named the calcitonin-like receptor (CLR) and the intracellular accessory CGRP-receptor component protein (RCP). MIA-treatment increased mRNA for CLR in L3-4 DRG and CLR protein in medium and large joint afferent neurones.Conclusions. Our findings provide new and compelling evidence implicating a role for CGRP in peripheral sensitization in experimental OA. Our novel finding of CGRP mediated control of joint nociceptor mechanosensitivity suggests that the CGRP receptor system may be an important target for the modulation of pain during OA. CGRP receptor antagonists recently developed for migraine pain should be investigated for their efficacy against pain in OA. © 2014 American College of Rheumatology.

Publication metadata

Author(s): Bullock CM, Wookey P, Bennett A, Mobasheri A, Dickerson I, Kelly S

Publication type: Article

Publication status: Published

Journal: Arthritis & Rheumatology

Year: 2014

Volume: 66

Issue: 8

Pages: 2188-2200

Print publication date: 01/08/2014

Online publication date: 28/07/2014

Acceptance date: 01/04/2014

Date deposited: 06/11/2015

ISSN (print): 2326-5191

ISSN (electronic): 2326-5205

Publisher: John Wiley & Sons, Inc.

URL: http://dx.doi.org/10.1002/art.38656

DOI: 10.1002/art.38656

PubMed id: 24719311

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