The effect of WIN 55,212-2, a cannabinoid agonist, on tactile allodynia in diabetic rats.
The antinociceptive action of cannabinoids in acute and inflammatory pain states have been well-documented. There is also accumulating evidence suggesting that cannabinoids are effective analgesics in chronic pain conditions. WIN 55,212-2, a mixed CB1 and CB2 cannabinoid receptor agonist, has been shown to be effective against hyperalgesia and allodynia in painful peripheral mononeuropathy. Recently, in addition to their spinal and supraspinal antinociceptive action, cannabinoids have also reported to exert local analgesic effects. The aim of this study is to observe the effect of a high affinity cannabinoid, WIN 55,212-2, on tactile allodynia and thermal hyperalgesia in diabetic rats. Diabetes was produced with the injection of a single dose of streptozocin (50 mg/kg, i.p.) and this procedure resulted in neuropathic pain behaviors in the hindlimbs. Mechanical allodynia was detected by application of von Frey filaments to the plantar surface of the foot, and thermal hyperalgesia was studied using the Hargreaves' method; however, thermal hyperalgesia did not develop in diabetic rats. With its higher doses, both systemic (3 and 10 mg/kg, i.p.) and peripheral (30 microg, i.p.l.) injections of WIN 55,212-2 reduced mechanical allodynia. These results suggest that WIN 55,212-2 has an antiallodynic effect in streptozocin-induced diabetic rats and may be a promising approach in the treatment of diabetic neuropathy.
Ulugol
Ahmet
A
Department of Pharmacology, Faculty of Medicine, Trakya University, 22030-Edirne, Turkey. aulugol@trakya.edu.tr
Karadag
Hakan C
HC
Ipci
Yesim
Y
Tamer
Melek
M
Dokmeci
Ismet
I
D000818:Animals; D048588:Benzoxazines; D002186:Cannabinoids / Q000494:pharmacology* / Q000627:therapeutic use; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D008297:Male; D009025:Morpholines / Q000494:pharmacology* / Q000627:therapeutic use; D009281:Naphthalenes / Q000494:pharmacology* / Q000627:therapeutic use; D010147:Pain Measurement / Q000187:drug effects* / Q000379:methods; D051381:Rats; D017208:Rats, Wistar; D014110:Touch / Q000187:drug effects* / Q000502:physiology
D048588:Benzoxazines; 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