Abstract | OBJECTIVE: METHODS: 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.
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Authors | Craig M Bullock, Peter Wookey, Andrew Bennett, Ali Mobasheri, Ian Dickerson, Sara Kelly |
Journal | Arthritis & rheumatology (Hoboken, N.J.)
(Arthritis Rheumatol)
Vol. 66
Issue 8
Pg. 2188-200
(Aug 2014)
ISSN: 2326-5205 [Electronic] United States |
PMID | 24719311
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | © 2014 The Authors. Arthritis & Rheumatology is published by Wiley Periodicals, Inc. on behalf of the American College of Rheumatology. |
Chemical References |
- Receptors, Calcitonin Gene-Related Peptide
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Topics |
- Animals
- Arthritis, Experimental
- Disease Models, Animal
- Male
- Mechanical Phenomena
- Osteoarthritis
(complications, physiopathology)
- Pain
(etiology)
- Rats
- Rats, Sprague-Dawley
- Receptors, Calcitonin Gene-Related Peptide
(physiology)
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