title: The effect of intra-articular capsaicin on nerve fibres within the synovium of the rat knee joint.
abstract: The aim of this study was to establish the effects of intra-articular capsaicin (pelargonic acid vallinylamide) on synovial innervation of the rat knee. Rats were sacrificed 1, 2, 4 and 7 days after intra-articular injection of capsaicin and joint tissues stained with either conventional haematoxylin and eosin (H and E) or with specific antibodies to the calcitonin gene-related peptide (CGRP), substance P (both of which are markers for primary afferent fibres), the C-flanking peptide of neuropeptide Y (CPON) (localised in postganglionic sympathetic fibres), or protein gene product 9.5 (a pan-neuronal marker). At lower concentrations (0.1% and 0.25%), capsaicin produced no change in peptide staining pattern or histological appearance. At 0.5% capsaicin, there was complete loss of nerve fibres showing positive staining for CGRP and substance P at all time points. Staining for CPON and protein gene product 9.5 was still present, but decreased, 1 and 2 days after treatment and virtually absent at 4 and 7 days. These findings provide evidence for partially selective denervation induced by 0.5% capsaicin, in contrast to 1% capsaicin which abolished staining for all peptide markers, indicating a total ablation of nerve fibres. A consistent but unexpected finding was the presence of a severe inflammatory response in joints treated with 0.5% and 1% capsaicin. An influx of polymorphonuclear leucocytes was found to occur within 4 h of injection, with progressive appearance of mononuclear cells after this time. We conclude that it is difficult to specifically deplete sensory nerve fibres from the synovium by means of local capsaicin injection. Although selective loss of staining for sensory nerve fibres could be achieved by injection of 0.5% capsaicin, there was progressive non-specific loss of post-ganglionic autonomic fibres which may be related to the severe inflammatory response provoked by the higher doses of capsaicin.
authors.affiliation: Inflammation Group, London Hospital Medical College, UK.
authors.forename: P I
authors.initials: PI
authors.lastname: Mapp
authors.forename: S
authors.initials: S
authors.lastname: Kerslake
authors.forename: S D
authors.initials: SD
authors.lastname: Brain
authors.forename: D R
authors.initials: DR
authors.lastname: Blake
authors.forename: H
authors.initials: H
authors.lastname: Cambridge
mesh_terms: D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000032:analysis / Q000187:drug effects; D002211:Capsaicin / Q000494:pharmacology*; D007150:Immunohistochemistry; D007249:Inflammation / Q000139:chemically induced; D007270:Injections, Intra-Articular; D007719:Knee Joint / Q000187:drug effects*; D007963:Leukocytes, Mononuclear / Q000166:cytology; D008297:Male; D009412:Nerve Fibers / Q000187:drug effects*; D009419:Nerve Tissue Proteins / Q000032:analysis / Q000187:drug effects; D009478:Neuropeptide Y / Q000032:analysis / Q000187:drug effects; D009504:Neutrophils / Q000166:cytology; D051381:Rats; D017208:Rats, Wistar; D013373:Substance P / Q000032:analysis / Q000187:drug effects; D013583:Synovial Membrane / Q000187:drug effects / Q000294:innervation*; D013869:Thiolester Hydrolases / Q000032:analysis / Q000187:drug effects; D043222:Ubiquitin Thiolesterase
chemical_list: D009419:Nerve Tissue Proteins; D009478:Neuropeptide Y; D013373:Substance P; D013869:Thiolester Hydrolases; D043222:Ubiquitin Thiolesterase; D015740:Calcitonin Gene-Related Peptide; D002211:Capsaicin