PMID:10771345

Citation	Minami, T, Okuda-Ashitaka, E, Mori, H, Sakimura, K, Watanabe, M, Mishina, M and Ito, S (2000) Characterization of nociceptin/orphanin FQ-induced pain responses in conscious mice: neonatal capsaicin treatment and N-methyl-D-aspartate receptor GluRepsilon subunit knockout mice. Neuroscience 97:133-42
Abstract	Activation of primary afferent C fibers gives rise to spinal release of substance P and glutamate, and these mediators facilitate the cascade of nociceptive processing. We recently showed that intrathecal administration of nociceptin or orphanin FQ (hereafter called nociceptin) induced hyperalgesia to noxious thermal stimuli and allodynia to innocuous tactile stimuli applied to conscious mice. In the present study, we designed experiments to elucidate the pathways and mediators of nociceptin-evoked pain responses. Neonatal capsaicin treatment eliminated the induction of hyperalgesia and allodynia by nociceptin. Whereas this treatment markedly reduced the content of substance P in the spinal cord, it did not affect the nociceptin content or the expression of nociceptin receptors and GluRvarepsilon and GluRzeta subunits 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 hyperalgesia, disappeared in N-methyl-D-aspartate receptor GluRvarepsilon1 subunit knockout mice. Both nociceptin-evoked hyperalgesia and allodynia were attenuated by morphine in a dose-dependent manner. Taken together, these results demonstrate that capsaicin-sensitive primary afferent fibers are involved not only in thermal hyperalgesia but also in tactile allodynia induced by nociceptin, but in different pathways; the former is mediated by substance P and the latter is mediated by glutamate through the N-methyl-D-aspartate receptor comprising the GluRvarepsilon1 subunit.
Links	PubMed
Keywords	Analgesics, Opioid/pharmacology; Animals; Animals, Newborn; Capsaicin/pharmacology; Consciousness/physiology; Immunohistochemistry; Injections, Spinal; Male; Mice; Mice, Knockout; Morphine/pharmacology; Nerve Fibers/drug effects; Nerve Fibers/metabolism; Nerve Fibers/ultrastructure; Nociceptors/drug effects; Nociceptors/physiology; Opioid Peptides/metabolism; Opioid Peptides/pharmacology; Pain/drug therapy; Pain/pathology; Pain/physiopathology; Posterior Horn Cells/metabolism; Receptors, N-Methyl-D-Aspartate/drug effects; Receptors, N-Methyl-D-Aspartate/metabolism; Substance P/metabolism; Time Factors; Vasodilator Agents/pharmacology
edit table

Annotations

Gene product	Qualifier	GO ID	GO term name	Evidence Code	with/from	Aspect	Notes	Status
edit table

References

See Help:References for how to manage references in GONUTS.