title: Nociceptin/orphanin FQ evokes knee joint pain in rats via a mast cell independent mechanism.
abstract: Nociceptin/orphanin FQ (N/OFQ) is an opioid-like neuropeptide that has been shown to cause peripheral sensitization of knee joint afferents; however, the effect of the peptide on joint pain behaviour is unknown. In addition to having a direct effect on peripheral nerves, N/OFQ has also been shown to activate connective tissue mast cells causing the local release of potentially pain causing mediators. The present study tested the effect of peripherally administered N/OFQ on joint pain and examined whether synovial mast cells contribute to these responses. Hindlimb weight bearing and von Frey hair algesiometry were measured before and following a single injection of N/OFQ in the vicinity of the right knee of male Wistar rats. Compared to saline-treated controls, N/OFQ caused a conspicuous shift in hindlimb weight bearing in favour of the contralateral non-injected leg. Similarly, paw withdrawal threshold and latency were significantly reduced following N/OFQ administration indicative of secondary hyperalgesia. To test the involvement of synovial mast cells in these pain reactions, a separate group of rats were treated with the mast cell stabilizer cromolyn (20 mg/kg s.c.) 5 min prior to N/OFQ injection. Cromolyn treatment had no significant effect on N/OFQ-induced weight bearing deficit nor secondary hyperalgesic responses. In conclusion, these data support the premise that N/OFQ has a pain causing effect in the periphery which occurs independently of mast cell activation.
authors.affiliation: Department of Physiology & Biophysics, University of Calgary, 3330, Hospital Drive NW, Calgary, Alta., Canada T2N 4N1. mcdougaj@ucalgary.ca
authors.forename: Jason J
authors.initials: JJ
authors.lastname: McDougall
authors.forename: Sarah E M
authors.initials: SE
authors.lastname: Larson
mesh_terms: D000818:Animals; D006614:Hindlimb; D007596:Joints / Q000187:drug effects / Q000503:physiopathology*; D008297:Male; D008407:Mast Cells / Q000502:physiology*; D018847:Opioid Peptides / Q000494:pharmacology / Q000502:physiology*; D010146:Pain / Q000503:physiopathology*; D010147:Pain Measurement; D051381:Rats; D017208:Rats, Wistar; D013583:Synovial Membrane / Q000473:pathology; D016474:Weight-Bearing; D000097629:Nociceptin
chemical_list: D018847:Opioid Peptides; D000097629:Nociceptin