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

Bullock, CM, Wookey, P, Bennett, A, Mobasheri, A, Dickerson, I and Kelly, S (2014) Peripheral Calcitonin Gene-Related Peptide Receptor Activation and Mechanical Sensitization of the Joint in Rat Models of Osteoarthritis Pain ARTHRITIS & RHEUMATOLOGY, 66 (8). pp. 2188-2200.

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Abstract

OBJECTIVE: To investigate the role of the sensory neuropeptide calcitonin gene-related peptide (CGRP) in peripheral sensitization in experimental models of osteoarthritis (OA) pain. METHODS: Experimental knee OA was induced in rats by intraarticular injection of monosodium iodoacetate (MIA) or by transection of the medial meniscus (MMT). Single-unit recordings of joint-innervating nociceptors were obtained in MIA- and saline-treated rats following administration of CGRP or the CGRP receptor antagonist CGRP 8-37. Effects of CGRP 8-37 were also examined in rats that underwent MMT and sham operations. Protein and messenger RNA (mRNA) levels of CGRP receptor components in the L3-L4 dorsal root ganglion (DRG) were investigated following MIA treatment. RESULTS: In both the MIA and MMT groups, the mechanical sensitivity of joint nociceptors was enhanced compared to that in the control groups. Exogenous CGRP increased mechanical sensitivity in a greater proportion of joint nociceptors in the MIA-treated rats than in the saline-treated rats. Local blockade of endogenous CGRP by CGRP 8-37 reversed both the MIA- and MMT-induced enhancement of joint nociceptor responses. Joint afferent cell bodies coexpressed the receptor for CGRP, called the calcitonin-like receptor (CLR), and the intracellular accessory CGRP receptor component protein. MIA treatment increased the levels of mRNA for CLR in the L3-L4 DRG and the levels of CLR protein in medium and large joint afferent neurons. CONCLUSION: Our findings provide new and compelling evidence implicating a role of 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.

Item Type: Article
Divisions : Faculty of Health and Medical Sciences > School of Veterinary Medicine
Authors :
AuthorsEmailORCID
Bullock, CMUNSPECIFIEDUNSPECIFIED
Wookey, PUNSPECIFIEDUNSPECIFIED
Bennett, AUNSPECIFIEDUNSPECIFIED
Mobasheri, AUNSPECIFIEDUNSPECIFIED
Dickerson, IUNSPECIFIEDUNSPECIFIED
Kelly, SUNSPECIFIEDUNSPECIFIED
Date : 1 August 2014
Identification Number : 10.1002/art.38656
Uncontrolled Keywords : Science & Technology, Life Sciences & Biomedicine, Rheumatology, AXONAL PROTEIN-SYNTHESIS, ROOT GANGLION NEURONS, MONOSODIUM IODOACETATE, SENSORY NEURONS, KNEE-JOINT, MODULATION, LOCALIZATION, INFLAMMATION, BEHAVIOR, HYPEREXCITABILITY
Related URLs :
Additional Information : © 2014 The Authors. Arthritis & Rheumatology is published by Wiley Periodicals, Inc. on behalf of the American College of Rheumatology. This is an open access article under the terms of the Creative Commons Attribution NonCommercial License, which permits use, distribution, and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
Depositing User : Symplectic Elements
Date Deposited : 23 Dec 2015 10:27
Last Modified : 23 Dec 2015 10:27
URI: http://epubs.surrey.ac.uk/id/eprint/809560

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