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
GM, Scoto;Simone, Ronsisvalle;
2012-01-01
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 stateFile | Dimensione | Formato | |
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Effects of intraplantar nocistatin pharmacology bichemistry and behav 2012.pdf
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