title: Cannabinoids blocks tactile allodynia in diabetic mice without attenuation of its antinociceptive effect.
abstract: Diabetic neuropathic pain is one of the most commonly encountered neuropathic pain syndromes. However, the treatment of diabetic neuropathic pain is challenging because of partial effectiveness of currently available pain relievers. It is well known that diabetic animals are less sensitive to the analgesic effect of morphine, and opioids are found to be ineffective in the treatment of diabetic neuropathic pain. Cannabinoids are promising drugs and they share a similar pharmacological properties with opioids. It has been reported that cannabinoid analgesia remained intact and to be effective in some models of nerve injury. Thus, we investigated antinociceptive efficacy and the effects of cannabinoids on behavioral sign of diabetic neuropathic pain in diabetic mice by using WIN 55, 212-2, a cannabinoid receptor agonist. Diabetes was induced by streptozotocin (STZ) (200mg/kg) and animals were tested between 45 and 60 days after onset of diabetes. Antinociception was assessed using the radiant tail-flick test. Mechanical and thermal sensitivities were measured by Von Frey filaments and hot-plate test, respectively. Tactile allodynia, but not thermal hyperalgesia developed in diabetic mice. Systemic WIN 55, 212-2 (1, 5 and 10mg/kg) produced a dose-dependent antinociception both in diabetic and control mice. WIN 55, 212-2-induced antinociception were found to be similar in diabetic mice when compared to controls suggesting efficacy of cannabinoid antinociception was not diminished in diabetic mice. WIN 55, 212-2 also produced a dose-dependent antiallodynic effect in diabetic mice. This study suggests that cannabinoids have a potential beneficial effect on experimental diabetic neuropathic pain.
authors.affiliation: Department of Pharmacology, Gülhane Academy of Medicine, 06018 Etlik, Ankara, Turkey. dogrula@gata.edu.tr
authors.forename: Ahmet
authors.initials: A
authors.lastname: Doğrul
authors.forename: Hüsamettin
authors.initials: H
authors.lastname: Gül
authors.forename: Oğuzhan
authors.initials: O
authors.lastname: Yildiz
authors.forename: Ferruh
authors.initials: F
authors.lastname: Bilgin
authors.forename: M Erdal
authors.initials: ME
authors.lastname: Güzeldemir
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D048588:Benzoxazines; D063386:Cannabinoid Receptor Agonists; D002186:Cannabinoids / Q000494:pharmacology*; D003921:Diabetes Mellitus, Experimental / Q000150:complications* / Q000503:physiopathology; D004305:Dose-Response Relationship, Drug; D005260:Female; D006358:Hot Temperature; D051379:Mice; D008807:Mice, Inbred BALB C; D009025:Morpholines / Q000494:pharmacology; D009281:Naphthalenes / Q000494:pharmacology; D010146:Pain / Q000517:prevention & control*; D010147:Pain Measurement / Q000187:drug effects; D010812:Physical Stimulation; D011930:Reaction Time / Q000187:drug effects
chemical_list: D048588:Benzoxazines; D063386:Cannabinoid Receptor Agonists; D002186:Cannabinoids; D009025:Morpholines; D009281:Naphthalenes; C070417:(3R)-((2,3-dihydro-5-methyl-3-((4-morpholinyl)methyl)pyrrolo-(1,2,3-de)-1,4-benzoxazin-6-yl)(1-naphthalenyl))methanone