Calcitonin gene-related peptide receptor antagonists: beyond migraine pain--a possible analgesic strategy for osteoarthritis?
Osteoarthritis (OA) pain is poorly understood and managed, as current analgesics have only limited efficacy and unwanted side effect profiles. A broader understanding of the pathological mechanisms driving OA joint pain is vital for the development of improved analgesics. Both clinical and preclinical data suggest an association between joint levels of the sensory neuropeptide calcitonin gene-related peptide (CGRP) and pain during OA. Whether a direct causative link exists remains an important unanswered question. Given the recent development of small molecule CGRP receptor antagonists with clinical efficacy against migraine pain, the interrogation of the role of CGRP in OA pain mechanisms is extremely timely. In this article, we provide the background to the importance of CGRP in pain mechanisms and review the emerging clinical and preclinical evidence implicating a role for CGRP in OA pain. We suggest that the CGRP receptor antagonists developed for migraine pain warrant further investigation in OA.
Arthritis Research UK Pain Centre, School of Biosciences, University of Nottingham, Sutton Bonington Campus, Leicestershire, LE12 5RD, UK, stxcb1@nottingham.ac.uk.
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Bullock
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Kelly
D000700:Analgesics / Q000627:therapeutic use*; D015740:Calcitonin Gene-Related Peptide / Q000187:drug effects / Q000378:metabolism*; D000077221:Calcitonin Gene-Related Peptide Receptor Antagonists; D005260:Female; D006801:Humans; D008297:Male; D008881:Migraine Disorders / Q000188:drug therapy* / Q000503:physiopathology; D059225:Nociception / Q000187:drug effects; D010003:Osteoarthritis / Q000188:drug therapy* / Q000503:physiopathology; D010146:Pain / Q000188:drug therapy* / Q000503:physiopathology; D018015:Receptors, Calcitonin Gene-Related Peptide / Q000378:metabolism; D016896:Treatment Outcome
D000700:Analgesics; D000077221:Calcitonin Gene-Related Peptide Receptor Antagonists; D018015:Receptors, Calcitonin Gene-Related Peptide; D015740:Calcitonin Gene-Related Peptide