Spinal analgesic activity of orphanin FQ/nociceptin and its fragments.
Previous work reveals that orphanin FQ/nociceptin (OFQ/N) administered supraspinally produces an initial hyperalgesic response followed by analgesia. Spinally, OFQ/N elicits a rapidly appearing, naltrexone-reversible, dose-dependent analgesia in the tailflick assay without any indication of hyperalgesia. Two OFQ/N fragments, OFQ/N (1-7) and OFQ/N (1-11), are active, but far weaker. Blockade of sigma receptors with haloperidol enhances the analgesic potency of spinal OFQ/N, OFQ/N (1-7) and OFQ/N (1-11), but not as dramatically as supraspinal OFQ. Antisense probes targeting the second and third coding exons, but not the first exon, of the cloned mouse OFQ/N receptor (KOR-3) partially block OFQ/N analgesia.
King
M A
MA
George Cotzias Laboratory of Neuro-Oncology, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.
Rossi
G C
GC
Chang
A H
AH
Williams
L
L
Pasternak
G W
GW
D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D016375:Antisense Elements (Genetics) / Q000494:pharmacology; D003001:Cloning, Molecular; D004357:Drug Synergism; D005091:Exons; D006220:Haloperidol / Q000494:pharmacology; D006930:Hyperalgesia / Q000139:chemically induced; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D018847:Opioid Peptides / Q000494:pharmacology*; D010446:Peptide Fragments / Q000494:pharmacology*; D011957:Receptors, Opioid / Q000819:agonists* / Q000187:drug effects / Q000235:genetics; D017480:Receptors, sigma / Q000037:antagonists & inhibitors; D013116:Spinal Cord / Q000187:drug effects*; D000094942:Nociceptin Receptor; D000097629:Nociceptin
D000700:Analgesics; D016375:Antisense Elements (Genetics); D006220:Haloperidol; D018847:Opioid Peptides; D010446:Peptide Fragments; D011957:Receptors, Opioid; D017480:Receptors, sigma; D000094942:Nociceptin Receptor; D000097629:Nociceptin; C000722287:Oprl1 protein, mouse