Effect of systemic FR140423, a new analgesic compound, in a rat model of postoperative pain: contribution of delta-opioid receptors.
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.
Ochi
Takehiro
T
Department of Immunology and Inflammation, Medicinal Biology Research Laboratories, Fujisawa Pharmaceutical Co., Ltd., 1-6, Kashima 2-chome, Yodogawa-ku, Osaka, 532-8514, Japan. takehiro_ochi@po.fujisawa.co.jp
Ohkubo
Yoshitaka
Y
Mutoh
Seitaro
S
D000700:Analgesics / Q000627:therapeutic use*; D000818:Animals; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D006930:Hyperalgesia / Q000188:drug therapy; D008297:Male; D009020:Morphine / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000145:classification / Q000494:pharmacology; D017288:Pain Threshold / Q000187:drug effects; D010149:Postoperative Pain / Q000188:drug therapy*; D011720:Pyrazoles / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017465:Receptors, Opioid, delta / Q000378:metabolism*; D013454:Sulfoxides / Q000627:therapeutic use*
D000700:Analgesics; D009292:Narcotic Antagonists; D011720:Pyrazoles; D017465:Receptors, Opioid, delta; D013454:Sulfoxides; C108904:3-(difluoromethyl)-1-(4-methoxyphenyl)-5-(4-(methylsulfinyl)phenyl)pyrazole; D009020:Morphine