Effect of systemic FR140423, a new analgesic compound, in a rat model of postoperative pain: contribution of delta-opioid receptors.

Abstract

We investigated the anti-hyperalgesic effect of FR140423, 3-(difluoromethyl)-1-(4-methoxyphenyl-5-[4-(methylsulfinyl)phenyl]pyrazole, in a rat model of postoperative pain. Oral administration of FR140423 at doses between 1 and 100 mg/kg after surgery dose dependently attenuated the punctate mechanical hyperalgesia caused by an incision of the plantar surface of the hind paw with an ED50 value of 59 mg/kg. The anti-hyperalgesic effect of systematically administered FR140423 was blocked by naloxone, a non-selective opioid receptor antagonist. Furthermore, the delta-opioid receptor antagonist naltrindole (0.2 mg/kg) reversed anti-hyperalgesia induced by FR140423. Naloxonazine and nor-binaltorphimine failed to antagonize the anti-hyperalgesic effect of FR140423. The action of FR140423 differs from the naloxonazine-reversible anti-hyperalgesia induced by morphine. The present findings suggest that delta-opioid systems play a role in the rat anti-hyperalgesia produced by FR140423 for postoperative pain characterized by mechanical hyperalgesia.

• Authors: Takehiro Ochi, Yoshitaka Ohkubo, Seitaro Mutoh
• Journal: Neuroscience letters (Neurosci Lett) Vol. 350 Issue 1 Pg. 29-32 (Oct 16 2003) ISSN: 0304-3940 [Print] Ireland
• PMID: 12962910 (Publication Type: Comparative Study, Journal Article)

Chemical References

• Analgesics
• Narcotic Antagonists
• Pyrazoles
• Receptors, Opioid, delta
• Sulfoxides
• 3-(difluoromethyl)-1-(4-methoxyphenyl)-5-(4-(methylsulfinyl)phenyl)pyrazole
• Morphine

Topics

• Analgesics (therapeutic use)
• Animals
• Disease Models, Animal
• Dose-Response Relationship, Drug
• Drug Interactions
• Hyperalgesia (drug therapy)
• Male
• Morphine (pharmacology)
• Narcotic Antagonists (classification, pharmacology)
• Pain Threshold (drug effects)
• Pain, Postoperative (drug therapy)
• Pyrazoles (therapeutic use)
• Rats
• Rats, Sprague-Dawley
• Receptors, Opioid, delta (metabolism)
• Sulfoxides (therapeutic use)