Long-lasting antinociceptive spinal effects in primates of the novel nociceptin/orphanin FQ receptor agonist UFP-112

Pain. 2010 Jan;148(1):107-113. doi: 10.1016/j.pain.2009.10.026. Epub 2009 Nov 28.


Chemical modifications of nociceptin/orphanin FQ (N/OFQ) peptide that result in increased potency and resistance to degradation have recently lead to the discovery of [(pF)Phe(4)Aib(7)Arg(14)Lys(15)]N/OFQ-NH(2) (UFP-112), a novel N/OFQ peptide (NOP) receptor agonist. The aim of this study was to investigate the pharmacological profile of intrathecally administered UFP-112 in monkeys under different behavioral assays. Intrathecal UFP-112 (1-10 nmol) dose-dependently produced antinociception against an acute noxious stimulus (50 degrees C water) and capsaicin-induced thermal hyperalgesia. Intrathecal UFP-112-induced antinociception could be reversed by a NOP receptor antagonist, J-113397 (0.1mg/kg), but not by a classic opioid receptor antagonist, naltrexone (0.03 mg/kg). Like intrathecal morphine, UFP-112 produced antinociception in two primate pain models with a similar magnitude of effectiveness and a similar duration of action that last for 4-5h. Unlike intrathecal morphine, UFP-112 did not produce itch/scratching responses. In addition, intrathecal inactive doses of UFP-112 and morphine produced significant antinociceptive effects when given in combination without increasing scratching responses. These results demonstrated that intrathecal UFP-112 produced long-lasting morphine-comparable antinociceptive effects without potential itch side effect. This study is the first to provide functional evidence that selective NOP receptor agonists such as UFP-112 alone or in conjunction with morphine may improve the quality of spinal analgesia.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Analgesics / therapeutic use*
  • Animals
  • Benzimidazoles / pharmacology
  • Capsaicin / adverse effects
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Female
  • Hyperalgesia / chemically induced
  • Hyperalgesia / drug therapy*
  • Hyperalgesia / physiopathology
  • Injections, Spinal / methods
  • Macaca mulatta
  • Male
  • Morphine / therapeutic use
  • Naltrexone / pharmacology
  • Opioid Peptides / agonists*
  • Opioid Peptides / therapeutic use*
  • Pain Measurement
  • Pain Threshold / drug effects
  • Piperidines / pharmacology


  • Analgesics
  • Benzimidazoles
  • J 113397
  • Opioid Peptides
  • Piperidines
  • nociceptin-amide, Nphe(1)-(pF)Phe(4)-Aib(7)-Arg(14)-Lys(15)-
  • Naltrexone
  • Morphine
  • nociceptin
  • Capsaicin