Characterization of nociceptin/orphanin FQ-induced pain responses in conscious mice: Neonatal capsaicin treatment and N-methyl-D-aspartate receptor GluR epsilon subunit knockout mice

Activation of primary afferent C fibers gives rise to spinal release of sub stance P and glutamate, and these mediators facilitate the cascade of nocic eptive processing. We recently showed that intrathecal administration of no ciceptin or orphanin FQ thereafter called nociceptin) induced hyperalgesia to noxious thermal stimuli and allodynia to innocuous tactile stimuli appli ed to conscious mice. In the present study, we designed experiments to eluc idate the pathways and mediators of nociceptin-evoked pain responses. Neona tal capsaicin treatment eliminated the induction of hyperalgesia and allody nia by nociceptin. Whereas this treatment markedly reduced the content of s ubstance P in the spinal cord, it did not affect the nociceptin content or the expression of nociceptin receptors and GluR epsilon and GluR xi subunit s of N-methyl-D-aspartate receptors in it. The substance P antagonists CP96 ,345 and CP99,994 blocked the nociceptin-induced hyperalgesia, but not the allodynia. In contrast, the nociceptin-evoked allodynia, but not hyperalges ia, disappeared in N-methyl-D-aspaaate receptor GluR epsilon 1 subunit knoc kout mice. Both nociceptin-evoked hyperalgesia and allodynia were attenuate d by morphine in a dose-dependent manner. Taken together, these results dem onstrate that capsaicin-sensitive primary afferent fibers are involved not only in thermal hyperalgesia but also in tactile allodynia induced by nocic eptin, but in different pathways; the former is mediated by substance P and the latter is mediated by glutamate through the N-methyl-D-aspartate recep tor comprising the GluR epsilon 1 subunit. (C) 2000 IBRO. Published by Else vier Science Ltd.