In vivo pain-inhibitory role of nociceptin/orphanin FQ in spinal cord.
Because nociceptin/orphanin FQ (N/OFQ) has both pronociceptive (hyperalgesia) and antinociceptive actions in pharmacological experiments, and there is no significant difference in the nociceptive responses between NOP(-/-) mice and their wild-type (NOP(+/+)) littermates, the physiological role of N/OFQ in pain regulation remains to be determined. Under the hypothesis that the use of molecularly distinct nociception test may reveal the pain modality-specific role of N/OFQ, we attempted to examine the physiological role of N/OFQ in pain transmission by using newly developed algogenic-induced nociceptive flexion test in NOP(-/-) and NOP(+/+) mice or NOP antagonist-treated mice. The nociceptive flexor responses upon intraplantar injection of bradykinin or substance P, which stimulates polymodal substance P-ergic fibers, were markedly potentiated in NOP(-/-) mice, compared with those in its NOP(+/+) mice. However, there were no significant changes in NOP(-/-) mice with adenosine triphosphate or prostaglandin I(2) agonist, which stimulates glutamatergic but not substance P-ergic fibers. The nocifensive responses induced by substance P (i.t.) were also potentiated in NOP(-/-) mice. On the other hand, there were no significant differences in NK1-like immunoreactivity, [(3)H]substance P binding, or NK1 gene expression in the dorsal horn of the spinal cord between NOP(-/-) and NOP(+/+) mice. In addition, NOP antagonists decreased the threshold in nociception tests driving spinal substance P neurotransmission. All these findings suggest that the N/OFQ-ergic neuron may play an in vivo inhibitory role on the second-order neurons for primary polymodal substance P-ergic fibers in the spinal cord.
Inoue
Makoto
M
Division of Molecular Pharmacology and Neuroscience, Nagasaki University Graduate School of Biomedical Sciences, 1-14 Bunkyo-machi, Nagasaki 852-8521, Japan. ueda@net.nagasaki-u.ac.jp
Kawashima
Toshiko
T
Takeshima
Hiroshi
H
Calo
Girolamo
G
Inoue
Atsuko
A
Nakata
Yoshihiro
Y
Ueda
Hiroshi
H
D000818:Animals; D015153:Blotting, Western; D002211:Capsaicin; D004305:Dose-Response Relationship, Drug; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D006358:Hot Temperature; D007150:Immunohistochemistry; D007278:Injections, Spinal; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D016202:N-Methylaspartate / Q000494:pharmacology; D064729:Neurokinin-1 Receptor Antagonists; D018847:Opioid Peptides / Q000235:genetics / Q000502:physiology*; D010146:Pain / Q000503:physiopathology*; D010147:Pain Measurement; D011312:Pressure; D018040:Receptors, Neurokinin-1 / Q000096:biosynthesis; D012018:Reflex / Q000187:drug effects; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013116:Spinal Cord / Q000502:physiology*; D013373:Substance P / Q000494:pharmacology / Q000502:physiology; D013570:Synaptic Membranes / Q000187:drug effects / Q000378:metabolism; D009435:Synaptic Transmission / Q000187:drug effects; D000097629:Nociceptin
D002211:Capsaicin; D018690:Excitatory Amino Acid Agonists; D016202:N-Methylaspartate; D064729:Neurokinin-1 Receptor Antagonists; D018847:Opioid Peptides; D018040:Receptors, Neurokinin-1; D013373:Substance P; D000097629:Nociceptin