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Veterinary journal (London, England : 1997)2012; 196(1); 40-46; doi: 10.1016/j.tvjl.2012.07.030

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.
Publication Date: 2012-08-28 PubMed ID: 22939088DOI: 10.1016/j.tvjl.2012.07.030Google Scholar: Lookup
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  • Journal Article
  • Randomized Controlled Trial

Summary

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This research investigated how acute inflammation may increase µ-opioid receptors (MOR) in equine synovial membranes, and whether anti-inflammatory treatment could prevent this increase. Results indicate that inflammation does up-regulate MORs, but anti-inflammatory treatment may mitigate this response.

Methodology

  • The study used a two-period, blinded, placebo-controlled randomized cross-over design.
  • Seven healthy ponies were injected with lipopolysaccharide (LPS, 1.0 ng) into the left or right middle carpal joint. This substance induces localized infection-like symptoms, effectively simulating an inflammatory condition.
  • Arthroscopy and synovial membrane biopsies were performed under general anaesthesia at three phases: baseline, 48 hours (T48), and 672 hours (T672) after LPS injection.
  • Ponies received either phenylbutazone (PBZ 2.2mg/kg PO BID), which is an anti-inflammatory medication, or a placebo starting from 2 hours post-LPS injection.
  • Pain and lameness, indicative of discomfort, were scored to evaluate the effectiveness of the treatment.
  • Synovitis, inflammation of the joint lining, was evaluated both macroscopically and microscopically using repeated synovial fluid samples.
  • Immunohistochemical techniques were used to determine any changes in the density and staining pattern of MOR-like protein in synovial membrane biopsies over the duration of the inflammation, with or without PBZ treatment.

Key Findings

  • The injection of LPS consistently triggered a severe transient synovitis, simulating the effects of acute inflammation.
  • Significant pain and lameness were observed following the injection, indicating the effectiveness of the method in inducing inflammation.
  • PBZ treatment significantly decreased these symptoms, demonstrating its effectiveness as an anti-inflammatory medication in this context.
  • An increase in MOR-like protein was observed in the inflamed equine synovial membrane of the placebo-treated animals. This provides evidence that acute inflammation will up-regulate MOR.
  • However, this effect was not observed in the PBZ-treated animals, providing support to the idea that anti-inflammatory treatment could prevent such up-regulation.
  • While there were no significant differences at any individual time point between the two groups, the overall observation leads to the conclusion that inflammation can lead to upregulation of MORs, but this can be potentially limited with effective anti-inflammatory treatment.

Cite This Article

APA
van Loon JP, de Grauw JC, Brunott A, Weerts EA, van Weeren PR. (2012). Upregulation of articular synovial membrane μ-opioid-like receptors in an acute equine synovitis model. Vet J, 196(1), 40-46. https://doi.org/10.1016/j.tvjl.2012.07.030

Publication

ISSN: 1532-2971
NlmUniqueID: 9706281
Country: England
Language: English
Volume: 196
Issue: 1
Pages: 40-46
PII: S1090-0233(12)00340-1

Researcher Affiliations

van Loon, J P A M
  • Department of Equine Sciences, Faculty of Veterinary Medicine, Utrecht University, Yalelaan 114, 3584 CM Utrecht, The Netherlands. j.p.a.m.vanloon@uu.nl
de Grauw, J C
    Brunott, A
      Weerts, E A W S
        van Weeren, P R

          MeSH Terms

          • Animals
          • Anti-Inflammatory Agents, Non-Steroidal / therapeutic use
          • Arthroscopy / veterinary
          • Blotting, Western / veterinary
          • Carpal Joints / metabolism
          • Carpal Joints / pathology
          • Cross-Over Studies
          • Escherichia coli / physiology
          • Horse Diseases / chemically induced
          • Horse Diseases / drug therapy
          • Horse Diseases / metabolism
          • Horses
          • Inflammation / chemically induced
          • Inflammation / drug therapy
          • Inflammation / metabolism
          • Inflammation / veterinary
          • Injections, Intra-Articular / veterinary
          • Lameness, Animal / chemically induced
          • Lameness, Animal / drug therapy
          • Lameness, Animal / metabolism
          • Lipopolysaccharides / administration & dosage
          • Lipopolysaccharides / immunology
          • Locomotion / drug effects
          • Male
          • Pain / drug therapy
          • Pain / veterinary
          • Phenylbutazone / therapeutic use
          • Receptors, Opioid, mu / metabolism
          • Synovial Fluid / metabolism
          • Synovial Membrane / metabolism
          • Synovitis / chemically induced
          • Synovitis / drug therapy
          • Synovitis / metabolism
          • Synovitis / veterinary
          • Up-Regulation

          Citations

          This article has been cited 2 times.
          1. Skiöldebrand E, Ley C, Björklund U, Lindahl A, Hansson E. Serotonin-evoked cytosolic Ca(2+) release and opioid receptor expression are upregulated in articular cartilage chondrocytes from osteoarthritic joints in horses. Vet Anim Sci 2019 Dec;8:100078.
            doi: 10.1016/j.vas.2019.100078pubmed: 32734095google scholar: lookup
          2. Varela L, van de Lest CHA, van Weeren PR, Wauben MHM. Synovial fluid extracellular vesicles as arthritis biomarkers: the added value of lipid-profiling and integrated omics. Extracell Vesicles Circ Nucl Acids 2024;5(2):276-296.
            doi: 10.20517/evcna.2024.14pubmed: 39698533google scholar: lookup