Attenuation of knee joint inflammation by peripherally administered endomorphin-1.

Abstract

Endomorphin-1 is a selective endogenous ligand for the micro-opioid receptor, and this study investigated the effect of endomorphin-1 on rat knee joint inflammation by examining the ability of the neuropeptide to modulate synovial protein extravasation. Acute joint inflammation was induced by intraarticular injection of 2% kaolin followed by 2% carrageenan and the animals allowed to recover for 3 h. Immunohistochemical examination of these inflamed joints revealed endomorphin-1-like immunoreactive nerves in deep synovium with a proportion of the nerve fibers occurring in close proximity to synovial blood vessels. Perfusion of inflamed knees with exogenous endomorphin-1 across the dose range 10-9-10-6 M produced a significant reduction in synovial vascular permeability with the 10-7M dose producing the greatest fall in protein exudation (approx 55%). These effects were blocked by the specific micro-opioid receptor antagonist CTOP. Destruction of knee joint unmyelinated afferent nerve fibers by capsaicin treatment significantly attenuated the anti-inflammatory effects of endomorphin-1, suggesting that the peptide is acting via a neurogenic mechanism. The findings of this study indicate that endomorphin-1 acts peripherally in knee joints to reduce synovial protein extravasation. These anti-inflammatory effects are mediated by micro-opioid receptors located on capsaicin-sensitive afferent nerves.

• Authors: Jason J McDougall, Chris L Baker, Petra M Hermann
• Journal: Journal of molecular neuroscience : MN (J Mol Neurosci) Vol. 22 Issue 1-2 Pg. 125-37 ( 2004) ISSN: 0895-8696 [Print] United States
• PMID: 14742917 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anti-Inflammatory Agents
• Narcotic Antagonists
• Neurotoxins
• Oligopeptides
• Receptors, Opioid, mu
• endomorphin 1
• Capsaicin

Topics

• Animals
• Anti-Inflammatory Agents (pharmacology)
• Arthritis (drug therapy, metabolism, physiopathology)
• Blood Vessels (drug effects, innervation, physiopathology)
• Capillary Permeability (drug effects, physiology)
• Capsaicin (pharmacology)
• Dose-Response Relationship, Drug
• Drug Administration Routes
• Knee Joint (blood supply, drug effects, physiopathology)
• Male
• Narcotic Antagonists (pharmacology)
• Nerve Fibers, Unmyelinated (drug effects, physiology)
• Neurogenic Inflammation (drug therapy, metabolism, physiopathology)
• Neurotoxins (pharmacology)
• Oligopeptides (pharmacology)
• Perfusion
• Peripheral Nerves (drug effects, physiopathology)
• Rats
• Rats, Wistar
• Receptors, Opioid, mu (drug effects, metabolism)
• Sensory Receptor Cells (drug effects, physiopathology)
• Synovial Membrane (blood supply, drug effects, physiopathology)