Spinal anandamide inhibits nociceptive transmission via cannabinoid receptor activation in vivo.
The endocannabinoid anandamide has affinity for cannabinoid and vanilloid receptors, which have opposing effects on nociceptive transmission. Effects of spinal administration of anandamide on innocuous and noxious evoked spinal neuronal responses in non-inflamed and carrageenin-inflamed rats were studied. Anandamide (0.1-50 microg/50 microl) had inconsistent effects in non-inflamed rats. Following carrageenin inflammation, anandamide (50 microg/50 microl) significantly reduced evoked neuronal responses, C-fibre mediated non-potentiated and post-discharge responses of neurones reduced to 65 +/- 5% and 57 +/- 10% of control, respectively. Effects of anandamide were blocked by SR141716A, a selective CB1 receptor antagonist. Spinal SR141716A (0.001-1 ng/50 microl) alone did not influence neuronal responses in inflamed rats. Spinal anandamide inhibited nociceptive transmission via CB1 receptors; following inflammation there is evidence for a loss of spinal endogenous cannabinoid tone.
Harris
J
J
School of Biomedical Sciences, University of Nottingham Medical School, Queen's Medical Centre, UK.
Drew
L J
LJ
Chapman
V
V
D000818:Animals; D001095:Arachidonic Acids / Q000494:pharmacology*; D063385:Cannabinoid Receptor Modulators; D002351:Carrageenan; D004558:Electric Stimulation; D063388:Endocannabinoids; D006614:Hindlimb; D007249:Inflammation / Q000139:chemically induced; D007278:Injections, Spinal; D009619:Nociceptors / Q000187:drug effects*; D010880:Piperidines / Q000494:pharmacology; D053284:Polyunsaturated Alkamides; D011720:Pyrazoles / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug / Q000037:antagonists & inhibitors / Q000502:physiology*; D012016:Reference Values; D000077285:Rimonabant; D009435:Synaptic Transmission / Q000187:drug effects* / Q000502:physiology*
D001095:Arachidonic Acids; D063385:Cannabinoid Receptor Modulators; D063388:Endocannabinoids; D010880:Piperidines; D053284:Polyunsaturated Alkamides; D011720:Pyrazoles; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug; D002351:Carrageenan; D000077285:Rimonabant; C078814:anandamide