Peripheral orphanin FQ/Nociceptin analgesia in the mouse

• Published in: Life sciences (1973) 1999, Vol.64 (22), p.2021-2028
• Main Authors: Kolesnikov, Yuri A., Pasternak, Gavril W.
• Format: Article
• Language: English
• Subjects: Analgesia; Analgesics, Opioid - administration & dosage; Analgesics, Opioid - metabolism; Animals; anti-opioid; Antisense Elements (Genetics) - genetics; Base Sequence; Exons; Injections, Subcutaneous; KOR-3; Male; Mice; Mice, Inbred ICR; Naloxone - analogs & derivatives; Naloxone - pharmacology; Narcotic Antagonists - pharmacology; Nerve Tissue Proteins - agonists; Nerve Tissue Proteins - genetics; Nerve Tissue Proteins - metabolism; Nociceptin; Nociceptin Receptor; opioid; Opioid Peptides - administration & dosage; Opioid Peptides - metabolism; opioid receptor; ORL1; Pain Measurement; Receptors, Opioid; topical
• ISSN: 0024-3205; 1879-0631
• DOI: 10.1016/S0024-3205(99)00149-6

Orphanin FQ/Nociceptin (OFQ/N) administered peripherally was an effective analgesic in the tailflick test in mice (ED 5016.3 μg) It had a peak effect at 5 min and lasted up to 30 min. The kappa 3 analgesic naloxone benzoylhydrazone was also active peripherally (ED 50 3.8 μg). The analgesic actions of both agents were blocked by naloxone. Neither OFQ/N(1–11) nor OFQ/N(1–7) had appreciable peripheral activity. Antisense mapping both compounds against the murine orphan opioid receptor (KOR-3) confirmed the importance of this clone in their actions. Antisense probes targeting the second and third coding exons significantly lowered the analgesic effects of both compounds. However, the antisense targeting the first coding exon blocked only the actions of OFQ/N and not kappa 3 analgesia.