title: Upregulation of articular synovial membrane μ-opioid-like receptors in an acute equine synovitis model.
abstract: Intra-articular injection of opioids provides analgesia in painful equine joints and μ-opioid receptors (MORs) have been demonstrated in equine synovial membranes. The aim of this study was to determine whether acute inflammatory conditions will lead to up-regulation of MOR in equine synovial membranes and whether anti-inflammatory treatment can prevent any such upregulation. In a two-period, blinded, placebo-controlled randomised cross-over design, lipopolysaccharide (LPS, 1.0 ng) was injected into the left or right middle carpal joint of seven healthy ponies. Arthroscopy and synovial membrane biopsy was performed under general anaesthesia at baseline, 48 h (T48) and 672 h (T672) after LPS injection, with ponies assigned to receive either phenylbutazone (PBZ 2.2mg/kg PO BID) or placebo from 2h post-LPS. Ponies were scored for pain and lameness. Repeated synovial fluid samples were obtained and the degree of synovitis scored both macroscopically and microscopically. The density and staining pattern of MOR-like protein in synovial membrane biopsies over the course of the synovitis with or without PBZ treatment was evaluated using immunohistochemical techniques. LPS injection consistently induced a severe transient synovitis. Pain and lameness were significantly attenuated by treatment with PBZ. Up-regulation of MOR-like protein in the inflamed equine synovial membrane could be demonstrated in the placebo treated animals, but not in the PBZ-treated animals overall, although there were no significant differences at any individual time-point between the two groups. It was concluded that acute inflammation will up-regulate MOR, while anti-inflammatory treatment will attenuate this response.
authors.affiliation: Department of Equine Sciences, Faculty of Veterinary Medicine, Utrecht University, Yalelaan 114, 3584 CM Utrecht, The Netherlands. j.p.a.m.vanloon@uu.nl
authors.forename: J P A M
authors.initials: JP
authors.lastname: van Loon
authors.forename: J C
authors.initials: JC
authors.lastname: de Grauw
authors.forename: A
authors.initials: A
authors.lastname: Brunott
authors.forename: E A W S
authors.initials: EA
authors.lastname: Weerts
authors.forename: P R
authors.initials: PR
authors.lastname: van Weeren
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D001182:Arthroscopy / Q000662:veterinary; D015153:Blotting, Western / Q000662:veterinary; D050824:Carpal Joints / Q000378:metabolism / Q000473:pathology; D018592:Cross-Over Studies; D004926:Escherichia coli / Q000502:physiology; D006734:Horse Diseases / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D006736:Horses; D007249:Inflammation / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism / Q000662:veterinary; D007270:Injections, Intra-Articular / Q000662:veterinary; D007794:Lameness, Animal / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D008070:Lipopolysaccharides / Q000008:administration & dosage / Q000276:immunology; D008124:Locomotion / Q000187:drug effects; D008297:Male; D010146:Pain / Q000188:drug therapy / Q000662:veterinary*; D010653:Phenylbutazone / Q000627:therapeutic use*; D017450:Receptors, Opioid, mu / Q000378:metabolism*; D013582:Synovial Fluid / Q000378:metabolism; D013583:Synovial Membrane / Q000378:metabolism*; D013585:Synovitis / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism / Q000662:veterinary*; D015854:Up-Regulation
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D008070:Lipopolysaccharides; D017450:Receptors, Opioid, mu; D010653:Phenylbutazone