Antinociceptive Effects of Nociceptin/Orphanin FQ Administered Intrathecally in Monkeys

• Published in: The journal of pain Vol. 10; no. 5; pp. 509 - 516
• Main Authors: Ko, Mei-Chuan, Naughton, Norah N
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.05.2009
• Subjects: analgesia; Analgesics; Analgesics, Opioid - administration & dosage; Analgesics, Opioid - adverse effects; Analgesics, Opioid - pharmacology; Anesthesia & Perioperative Care; Animals; Behavior, Animal - drug effects; Dose-Response Relationship, Drug; Drug Synergism; Enkephalin, Ala-MePhe-Gly- - administration & dosage; Enkephalin, Ala-MePhe-Gly- - adverse effects; Enkephalin, Ala-MePhe-Gly- - pharmacology; Female; Hyperalgesia - psychology; Injections, Spinal; Macaca mulatta; Male; Morphine - adverse effects; Morphine - pharmacology; Nociceptin; NOP receptors; Opioid Peptides - administration & dosage; Opioid Peptides - adverse effects; Opioid Peptides - therapeutic use; Pain Measurement - drug effects; Pain Medicine; Pruritus - chemically induced; Receptors, Opioid - agonists; Spinal cord; substance P; Substance P - administration & dosage; Substance P - adverse effects; Substance P - pharmacology; thermal hyperalgesia; NOP receptors; thermal hyperalgesia; Spinal cord; substance P; analgesia
• ISSN: 1526-5900; 1528-8447
• DOI: 10.1016/j.jpain.2008.11.006

Abstract Nociceptin/orphanin FQ (N/OFQ) is the endogenous peptide for the NOP receptors. Depending on the doses, intrathecal administration of N/OFQ has dual actions (ie, hyperalgesia and antinociception) in rodents. However, the pharmacological profile of intrathecal N/OFQ is not fully known in primates. The aim of this study was to investigate behavioral effects of intrathecal N/OFQ over a wide dose range and to compare its effects with ligands known to produce hyperalgesia or antinociception in monkeys. Intrathecal N/OFQ from 1 fmol to 1 nmol did not produce any hyperalgesic or scratching responses. In contrast, intrathecal substance P 100 nmol produced hyperalgesia, and intrathecal DAMGO 10 nmol produced antinociception. At the dose range between 10 nmol and 1 μmol, intrathecal N/OFQ dose-dependently produced thermal antinociception against a noxious stimulus in 2 intensities. More importantly, N/OFQ in combined with intrathecal morphine dose-dependently potentiated morphine-induced antinociception without inhibiting morphine-induced itch/scratching. Taken together, this study is the first to provide a unique functional profile of intrathecal N/OFQ over a wide dose range in primates. Intrathecal N/OFQ produces thermal antinociception without anti-morphine actions or scratching responses, indicating that N/OFQ or NOP receptor agonists represent a promising target as spinal analgesics. Perspective Intrathecal administration of N/OFQ only produced thermal antinociception, not hyperalgesia, in monkeys. In addition, intrathecal N/OFQ does not have anti-morphine actions or itch/scratching responses. This study strongly supports the therapeutic potential of N/OFQ or NOP receptor agonists as spinal analgesics for clinical trials.