Nocistatin (NST) and Nociceptin/Orphanin FQ (N/OFQ) are derived from the same precursor protein, pre-proN/OFQ, and exert opposite effects on the modulation of pain signals. However, the role of the peripheral N/OFQ andthe NOP receptor, which is located at the endings of sensory nerves, in inflammatory pain was not ascertained.NST administered intrathecally (i.t.) prevented the nociceptive effects induced by i.t. N/OFQ and PGE2.Moreoveran up regulation of N/OFQ was shown in the rat in response to peripheral inflammation. Here, we investigatedthe effects of intraplantar (i.pl.) administration of functional N/OFQ and NOP receptor antagonists in a ratmodel of inflammatory pain. Our findings showed that i.pl. injection of (±)-J 113397, a selective antagonist ofthe NOP receptor, and NST, the functional N/OFQ antagonist, prior to carrageenan significantly reduced thepaw allodynic and thermal hyperalgesic threshold induced by the inflammatory agent. The resulting antiallodynicand antihyperalgesic effects by co-administering NST and (±)-J 113397 prior to carrageenan were markedlyenhanced, and the basal latencieswere restored. Thus, it is likely that the peripheral N/OFQ/NOP receptor systemcontributes to the abnormal pain sensitivity in an inflammatory state

Effects of intraplantar Nocistatin and (±)-J 113397 injections on nociceptive behavior in a rat model of inflammation

SCOTO, Giovanna Maria;RONSISVALLE, SIMONE;PARENTI, Carmela
2012

Abstract

Nocistatin (NST) and Nociceptin/Orphanin FQ (N/OFQ) are derived from the same precursor protein, pre-proN/OFQ, and exert opposite effects on the modulation of pain signals. However, the role of the peripheral N/OFQ andthe NOP receptor, which is located at the endings of sensory nerves, in inflammatory pain was not ascertained.NST administered intrathecally (i.t.) prevented the nociceptive effects induced by i.t. N/OFQ and PGE2.Moreoveran up regulation of N/OFQ was shown in the rat in response to peripheral inflammation. Here, we investigatedthe effects of intraplantar (i.pl.) administration of functional N/OFQ and NOP receptor antagonists in a ratmodel of inflammatory pain. Our findings showed that i.pl. injection of (±)-J 113397, a selective antagonist ofthe NOP receptor, and NST, the functional N/OFQ antagonist, prior to carrageenan significantly reduced thepaw allodynic and thermal hyperalgesic threshold induced by the inflammatory agent. The resulting antiallodynicand antihyperalgesic effects by co-administering NST and (±)-J 113397 prior to carrageenan were markedlyenhanced, and the basal latencieswere restored. Thus, it is likely that the peripheral N/OFQ/NOP receptor systemcontributes to the abnormal pain sensitivity in an inflammatory state
(±)-J 113397; Nocistatin; inflammation; hyperalgesia; allodynia; rat hind paw
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/20.500.11769/9642
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