Analgesic and antiinflammatory effects of cannabinoid receptor agonists in a rat model of neuropathic pain.
Cannabinoid receptor (CB) agonists are known to attenuate allodynia in a range of pain models, but their long-term effects and their mechanisms of action are controversial. The present study compares the antiallodynic effects of long-term treatment with a mixed CB1/CB2 (WIN55,212-2) and a selective CB2 (GW405833) cannabinoid receptor agonist and correlates these effects with their influences on spinal cord (SC) glial activation. The substances were applied daily in a rat neuropathic pain model. Tactile allodynia was assessed, and the development of gliosis was illustrated with immunohistochemical methods. Both substances reduced mechanical allodynia. Their analgesic effect was accompanied by a significant reduction in reactive gliosis and cathepsins (CAT) X and S expression. A daily injection of either substance for 8 days was sufficient to induce a sustained antiallodynic effect, which persisted up to 6 days after the last injection. The re-appearance of mechanical allodynia after this period was associated with a breakout of a strong gliotic response in the lumbar SC. Our results emphasize the therapeutic efficacy of cannabinoid receptor agonists and their inhibitory effects on the formation of gliosis.
Leichsenring
Anna
A
Animal Physiology, Biology and Biotechnology, ND5/132, Ruhr-University Bochum, 44780, Bochum, Germany.
Andriske
Michael
M
Bäcker
Ingo
I
Stichel
Christine C
CC
Lübbert
Hermann
H
D000700:Analgesics / Q000627:therapeutic use*; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D048588:Benzoxazines / Q000627:therapeutic use; D063386:Cannabinoid Receptor Agonists; D002186:Cannabinoids / Q000627:therapeutic use; D004195:Disease Models, Animal; D007211:Indoles / Q000494:pharmacology / Q000627:therapeutic use; D008297:Male; D009025:Morpholines / Q000494:pharmacology / Q000627:therapeutic use; D009281:Naphthalenes / Q000627:therapeutic use; D009437:Neuralgia / Q000188:drug therapy* / Q000473:pathology; D010146:Pain / Q000188:drug therapy* / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D043882:Receptors, Cannabinoid / Q000502:physiology
C463040:1-(2,3-dichlorobenzoyl)-5-methoxy-2-methyl-(2-(mopholin-4-yl)ethyl)-1H-indole; D000700:Analgesics; D000894:Anti-Inflammatory Agents, Non-Steroidal; D048588:Benzoxazines; D063386:Cannabinoid Receptor Agonists; D002186:Cannabinoids; D007211:Indoles; D009025:Morpholines; D009281:Naphthalenes; D043882:Receptors, Cannabinoid; C070417:(3R)-((2,3-dihydro-5-methyl-3-((4-morpholinyl)methyl)pyrrolo-(1,2,3-de)-1,4-benzoxazin-6-yl)(1-naphthalenyl))methanone