title: The additive antinociceptive interaction between WIN 55,212-2, a cannabinoid agonist, and ketorolac.
abstract: Combinations of nonsteroidal antiinflammatory drugs (NSAIDs) and opioids are widespread in the management of pain, allowing better analgesia with reduced side effects. Cannabinoids are promising analgesic drugs that have pharmacological properties similar to those of opioids. However, the beneficial effects of cannabinoids for pain treatment are counterbalanced by their psychotomimetic side effects. We designed the present study to evaluate the antinociceptive interaction between cannabinoids and NSAIDs in mice, using the acetic acid-induced writhing test and tail-flick test. Interactions were analyzed using isobolographic analysis. WIN 55,212-2, a cannabinoid agonist, and the NSAID ketorolac, either alone or in combination, produced dose-dependent antinociception in the writhing test. Isobolographic analysis showed additive interactions between WIN 55,212-2 and ketorolac when they were coadministered systemically. Ketorolac is inactive in the radiant heat tail-flick test in which WIN 55,212-2 was active. Ketorolac did not influence WIN 55,212-2-induced antinociception in the tail-flick test. This study demonstrated an additive antinociceptive interaction between WIN 55,212-2 and ketorolac in an inflammatory visceral pain model. The combination of cannabinoids and NSAIDs may have utility in the pharmacotherapy of pain.
authors.affiliation: Department of Pharmacology, Trakya University, Edirne, Turkey.
authors.forename: Ahmet
authors.initials: A
authors.lastname: Ulugöl
authors.forename: Filiz
authors.initials: F
authors.lastname: Ozyigit
authors.forename: Ozgür
authors.initials: O
authors.lastname: Yesilyurt
authors.forename: Ahmet
authors.initials: A
authors.lastname: Dogrul
mesh_terms: D000700:Analgesics / Q000008:administration & dosage*; D000818:Animals; D048588:Benzoxazines; D002186:Cannabinoids / Q000008:administration & dosage*; D052246:Cyclooxygenase 2 Inhibitors / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D007279:Injections, Subcutaneous; D020911:Ketorolac Tromethamine / Q000008:administration & dosage*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009025:Morpholines / Q000008:administration & dosage*; D009281:Naphthalenes / Q000008:administration & dosage*; D010146:Pain / Q000139:chemically induced; D010147:Pain Measurement
chemical_list: D000700:Analgesics; D048588:Benzoxazines; D002186:Cannabinoids; D052246:Cyclooxygenase 2 Inhibitors; D009025:Morpholines; D009281:Naphthalenes; D020911:Ketorolac Tromethamine; C070417:(3R)-((2,3-dihydro-5-methyl-3-((4-morpholinyl)methyl)pyrrolo-(1,2,3-de)-1,4-benzoxazin-6-yl)(1-naphthalenyl))methanone