title: Absence of nalbuphine anti-analgesia in the rat.
abstract: In humans, kappa agonist-antagonist opioids such as nalbuphine have been proposed to produce both analgesia and anti-analgesia by acting at distinct receptors. The anti-analgesia appears to be greater in men, which may contribute to the greater nalbuphine analgesia observed in women. Kappa agonist-antagonists are also known to produce sexually dimorphic antinociception in nonhuman species but are generally more potent in males; anti-analgesia has not been reported in animals. The aim of the present study was to determine if nalbuphine anti-analgesia can be detected in the rat. Since nalbuphine anti-analgesia is more sensitive to naloxone antagonism than its analgesic effect, low doses of naloxone were combined with nalbuphine. Using the Randall-Selitto paw-withdrawal test, nalbuphine (0.5-10 mg/kg) induced dose-dependent antinociception in the rat. The antinociceptive effect of nalbuphine (0.5 or 1 mg/kg) was not enhanced by lower doses of naloxone but was antagonized by higher doses. These data do not support the hypothesis that the naloxone-sensitive anti-analgesic effect of nalbuphine observed in humans is present in the rat and could explain, at least in part, the opposite direction of the sex differences for kappa agonist-antagonist opioid analgesia observed in these two species.
authors.affiliation: Department of Oral and Maxillofacial Surgery, University of California, San Francisco, CA 94143, USA.
authors.forename: Sachia G
authors.initials: SG
authors.lastname: Khasar
authors.forename: Robert W
authors.initials: RW
authors.lastname: Gear
authors.forename: Jon D
authors.initials: JD
authors.lastname: Levine
mesh_terms: D000698:Analgesia / Q000379:methods; D000701:Analgesics, Opioid / Q000494:pharmacology*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D008297:Male; D015999:Multivariate Analysis; D009266:Nalbuphine / Q000494:pharmacology*; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D010147:Pain Measurement / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time; D017473:Receptors, Opioid, kappa / Q000819:agonists*
chemical_list: D000701:Analgesics, Opioid; D009292:Narcotic Antagonists; D017473:Receptors, Opioid, kappa; D009270:Naloxone; D009266:Nalbuphine