Yonsei Med J.  2013 May;54(3):763-771. 10.3349/ymj.2013.54.3.763.

Effects of Co-Administration of Intrathecal Nociceptin/Orphanin FQ and Opioid Antagonists on Formalin-Induced Pain in Rats

• Lee H

• KMID: 1727895
• DOI: http://doi.org/10.3349/ymj.2013.54.3.763

Abstract

PURPOSE
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.
MATERIALS AND METHODS
I.t. N/OFQ was injected in different doses (1-10 nmol) via a lumbar catheter prior to a 50 microL 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), beta-funaltrexamine (1-10 nmol), and norbinaltorphimine (10 nmol), selective delta-, micro- and kappa-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 beta-funaltrexamine dose-dependently reversed the N/OFQ-induced attenuation of flinching responses in both phases; however, norbinaltorphimine did not.
CONCLUSION
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 delta- and micro-opioid receptors, but not kappa-opioid receptors, are involved in the antinociceptive effects of N/OFQ in the spinal cord of rats.

Keyword

Antinociception; formalin test; nociceptin/orphanin FQ; opioid receptor

MeSH Terms

Analgesics/administration & dosage/*pharmacology
Animals
Formaldehyde/toxicity
Injections, Spinal
Male
Naltrexone/administration & dosage/analogs & derivatives/pharmacology
Narcotic Antagonists/administration & dosage/*pharmacology
Opioid Peptides/administration & dosage/*pharmacology
Pain Measurement
Rats
Rats, Sprague-Dawley
Receptors, Opioid/*agonists/drug effects
Analgesics
Narcotic Antagonists
Opioid Peptides
Receptors, Opioid
Formaldehyde
Naltrexone