ANTIALLODYNIC AND ANTIHYPERALGESIC EFFECTS OF INTRAPLANTAR NOCISTATIN AND (±)-J 113397 IN INFLAMMATORY PAIN

Nociceptin/Orphanin FQ (N/OFQ) and Nocistatin (NST), two neuropeptides derived from the same precursor protein pre-proN/OFQ, have opposite effects in several biological function such as the modulation of pain. In particular, an up regulation of N/OFQ was shown in the rat in response to peripheral inflammation and NST administered intrathecally (i.t.) prevented the nociceptive effects induced by i.t. N/OFQ and PGE2. However, the role of the peripheral N/OFQ and the NOP receptor, which is located at the endings of sensory nerves, in inflammatory pain needs to be elucidated. To this regard, we administered a selective antagonist of the NOP receptor, (±)-J 113397, and the functional N/OFQ antagonist, NST, into the hind paw of rats treated with carrageenan. We observed that intraplantar injection of (±)-J 113397 or NST prior to carrageenan significantly reduced the paw allodynic and thermal hyperalgesic threshold induced by the inflammatory agent, measured with von Frey’s filaments and plantar test respectively. Moreover, the co-administration of (±)-J 113397 and NST prior to carrageenan induced an improved antiallodynic and antihyperalgesic effect. These results support the hypothesis that the peripheral N/OFQ/NOP receptor system could be involved, at peripheral level, in the abnormal pain sensitivity during an inflammatory state.