Repeated treatment with the synthetic cannabinoid WIN 55,212-2 reduces both hyperalgesia and production of pronociceptive mediators in a rat model of neuropathic pain.
The antinociceptive properties of cannabinoids in persistent pain are not fully elucidated. We investigated the effect of repeated treatment with the synthetic cannabinoid receptor agonist WIN 55,212-2 on the neuropathic pain induced in rats by chronic constriction of the sciatic nerve. WIN 55,212-2 administered daily throughout the development of neuropathy reversed the hyperalgesia, at a dose (0.1 mg x kg(-1), s.c.) that had no effect on the nociceptive responses of either paw contralateral to the sciatic ligation or of animals subjected to sham surgery. At 14 days after injury, the levels of mediators known to be involved in neuropathic pain, such as prostaglandin E2, NO and the neuronal NOS, were increased. Repeated treatment with WIN 55,212-2 abolished these increases. In the light of the current clinical need for neuropathic pain treatments, these findings indicate that cannabinoid agonists, at doses devoid of psychoactive effects, could constitute important compounds for the development of new analgesics.
Costa
B
B
Department of Biotechnology and Bioscience, University of Milan-Bicocca, Piazza della Scienza 2, Milan 20126, Italy. barbara.costa@unimib.it
Colleoni
M
M
Conti
S
S
Trovato
A E
AE
Bianchi
M
M
Sotgiu
M L
ML
Giagnoni
G
G
D000700:Analgesics / Q000627:therapeutic use*; D000818:Animals; D048588:Benzoxazines; D002186:Cannabinoids / Q000138:chemical synthesis / Q000494:pharmacology / Q000627:therapeutic use*; D015232:Dinoprostone / Q000096:biosynthesis / Q000378:metabolism; D004195:Disease Models, Animal; D004334:Drug Administration Schedule; D006358:Hot Temperature / Q000009:adverse effects; D006930:Hyperalgesia / Q000188:drug therapy* / Q000517:prevention & control; D007279:Injections, Subcutaneous; D008297:Male; D009025:Morpholines / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D009281:Naphthalenes / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D052248:Nitric Oxide Synthase Type I; D009619:Nociceptors / Q000187:drug effects / Q000502:physiology; D010147:Pain Measurement / Q000379:methods; D051381:Rats; D017208:Rats, Wistar; D043882:Receptors, Cannabinoid / Q000187:drug effects; D012584:Sciatic Nerve / Q000293:injuries / Q000378:metabolism; D020426:Sciatic Neuropathy / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism*; D013997:Time Factors
D000700:Analgesics; D048588:Benzoxazines; D002186:Cannabinoids; D009025:Morpholines; D009281:Naphthalenes; D043882:Receptors, Cannabinoid; D009569:Nitric Oxide; C070417:(3R)-((2,3-dihydro-5-methyl-3-((4-morpholinyl)methyl)pyrrolo-(1,2,3-de)-1,4-benzoxazin-6-yl)(1-naphthalenyl))methanone; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; C496322:Nos1 protein, rat; D015232:Dinoprostone