title: Regulation of calcitonin gene-related peptide and TRPV1 in a rat model of osteoarthritis.
abstract: Pain in osteoarthritis (OA) remains an intractable problem in a majority of patients, with many of the commonly prescribed analgesics providing insufficient relief and considerable side effects. However, the structural or mechanistic cause of OA pain is still unknown. Animal models to address this issue have only recently been established, with much of the research to date focused on tissue pathology rather than pain. We have previously compared the surgically induced partial medial meniscectomy and chemically induced intra-articular iodoacetate injection rat models of OA in the rat, with reference to pain behaviour. This demonstrated relevant tissue pathology in both models, but greater evidence of pain related behaviour in the iodoacetate induced model. Here we further investigate the iodoacetate model using Fast Blue backlabelling from the articular joint space to identify the cell bodies of primary sensory afferents from the knee at the L4 dorsal root ganglion. Expression of calcitonin gene-related peptide (CGRP) and the vanilloid receptor TRPV1 was quantified in these backlabelled cells and was enriched in the knee afferents in all animals studied, compared to the expression in neurons across the whole dorsal root ganglia (DRG). Analysis of the backlabelled population in the osteoarthritis model and controls showed an increase in both CGRP and TRPV1 expression in the iodoacetate model compared with control animals. Therefore, there is a potential role for CGRP and TRPV1 in the manifestation of pain behaviour accompanied by OA changes in the knee in the iodoacetate induced model.
authors.affiliation: Novartis Institute for Medical Sciences, London WC1E 6BS, UK.
authors.forename: Janet
authors.initials: J
authors.lastname: Fernihough
authors.forename: Clive
authors.initials: C
authors.lastname: Gentry
authors.forename: Stuart
authors.initials: S
authors.lastname: Bevan
authors.forename: Janet
authors.initials: J
authors.lastname: Winter
mesh_terms: D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism*; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors; D005727:Ganglia, Spinal / Q000166:cytology; D007461:Iodoacetates; D007473:Ion Channels / Q000378:metabolism*; D007719:Knee Joint / Q000294:innervation / Q000378:metabolism; D008297:Male; D009475:Neurons, Afferent / Q000378:metabolism; D020370:Osteoarthritis, Knee / Q000139:chemically induced / Q000150:complications / Q000378:metabolism*; D010146:Pain / Q000209:etiology / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D050916:TRPV Cation Channels
chemical_list: D004791:Enzyme Inhibitors; D007461:Iodoacetates; D007473:Ion Channels; D050916:TRPV Cation Channels; C493922:Trpv1 protein, rat; D015740:Calcitonin Gene-Related Peptide