Nociceptin/orphanin FQ evokes knee joint pain in rats via a mast cell independent mechanism

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.