title: 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.affiliation: Department of Physiology and Biophysics, McCaig Centre for Joint Injury and Arthritis Research, University of Calgary, Calgary, AB T2N 4N1 Canada. mcdougaj@ucalgary.ca
authors.forename: Jason J
authors.initials: JJ
authors.lastname: McDougall
authors.forename: Chris L
authors.initials: CL
authors.lastname: Baker
authors.forename: Petra M
authors.initials: PM
authors.lastname: Hermann
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D001168:Arthritis / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D001808:Blood Vessels / Q000187:drug effects / Q000294:innervation / Q000503:physiopathology; D002199:Capillary Permeability / Q000187:drug effects / Q000502:physiology; D002211:Capsaicin / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004333:Drug Administration Routes; D007719:Knee Joint / Q000098:blood supply / Q000187:drug effects* / Q000503:physiopathology; D008297:Male; D009292:Narcotic Antagonists / Q000494:pharmacology; D036421:Nerve Fibers, Unmyelinated / Q000187:drug effects / Q000502:physiology; D020078:Neurogenic Inflammation / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D009498:Neurotoxins / Q000494:pharmacology; D009842:Oligopeptides / Q000494:pharmacology*; D010477:Perfusion; D010525:Peripheral Nerves / Q000187:drug effects* / Q000503:physiopathology; D051381:Rats; D017208:Rats, Wistar; D017450:Receptors, Opioid, mu / Q000187:drug effects / Q000378:metabolism; D011984:Sensory Receptor Cells / Q000187:drug effects / Q000503:physiopathology; D013583:Synovial Membrane / Q000098:blood supply / Q000187:drug effects* / Q000503:physiopathology
chemical_list: D000893:Anti-Inflammatory Agents; D009292:Narcotic Antagonists; D009498:Neurotoxins; D009842:Oligopeptides; D017450:Receptors, Opioid, mu; C105293:endomorphin 1; D002211:Capsaicin