title: Effects of co-administration of intrathecal nociceptin/orphanin FQ and opioid antagonists on formalin-induced pain in rats.
abstract: OBJECTIVE
  Nociceptin/orphanin FQ (N/OFQ) as an endogeneous hexadecapeptide is known to exert antinociceptive effects spinally. The aims of this study were to demonstrate the antinociceptive effects of i.t. N/OFQ and to investigate the possible interaction between N/OFQ and endogenous opioid systems using selective opioid receptor antagonists in rat formalin tests.
  
  
  METHODS
  I.t. N/OFQ was injected in different doses (1-10 nmol) via a lumbar catheter prior to a 50 μL injection of 5% formalin into the right hindpaw of rats. Flinching responses were measured from 0-10 min (phase I, an initial acute state) and 11-60 min (phase II, a prolonged tonic state). To observe which opioid receptors are involved in the anti-nociceptive effect of i.t. N/OFQ in the rat-formalin tests, naltrindole (5-20 nmol), β-funaltrexamine (1-10 nmol), and norbinaltorphimine (10 nmol), selective δ-, μ- and κ-opioid receptor antagonists, respectively, were administered intrathecally 5 min after i.t. N/OFQ.
  
  
  RESULTS
  I.t. N/OFQ attenuated the formalin-induced flinching responses in a dose-dependent manner in both phases I and II. I.t. administration of naltrindole and β-funaltrexamine dose-dependently reversed the N/OFQ-induced attenuation of flinching responses in both phases; however, norbinaltorphimine did not.
  
  
  CONCLUSIONS
  I.t. N/OFQ exerted an antinociceptive effect in both phases of the rat-formalin test through the nociceptin opioid peptide receptor. In addition, the results suggested that δ- and μ-opioid receptors, but not κ-opioid receptors, are involved in the antinociceptive effects of N/OFQ in the spinal cord of rats.
authors.affiliation: Department of Anesthesiology and Pain Medicine, School of Medicine, Ewha Womans University, 1071 Anyangcheon-ro, Yangcheon-gu, Seoul 158-710, Korea. leehee@ewha.ac.kr
authors.forename: Heeseung
authors.initials: H
authors.lastname: Lee
mesh_terms: D000700:Analgesics / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D005557:Formaldehyde / Q000633:toxicity; D007278:Injections, Spinal; D008297:Male; D009271:Naltrexone / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D018847:Opioid Peptides / Q000008:administration & dosage / Q000494:pharmacology*; D010147:Pain Measurement; D051381:Rats; D017207:Rats, Sprague-Dawley; D011957:Receptors, Opioid / Q000819:agonists* / Q000187:drug effects; D000097629:Nociceptin
chemical_list: D000700:Analgesics; D005557:Formaldehyde; D009271:Naltrexone; D009292:Narcotic Antagonists; D018847:Opioid Peptides; D011957:Receptors, Opioid; D000097629:Nociceptin; C051844:norbinaltorphimine; C024524:beta-funaltrexamine; C055382:naltrindole
keywords: Antinociception; formalin test; nociceptin/orphanin FQ; opioid receptor
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