Intraplantar injection of anandamide inhibits mechanically-evoked responses of spinal neurones via activation of CB2 receptors in anaesthetised rats.
Anti-nociceptive effects of the endocannabinoid anandamide are well established. Anandamide has, however, also been shown to activate pro-nociceptive vanilloid 1 (VR1) receptors present on primary afferent nociceptors. The aim of the present study was to determine the effect of intraplantar injection of anandamide on dorsal spinal neuronal responses in control rats and rats with hindpaw carrageenan-induced inflammation. Effects of intraplantar administration of anandamide (50 microg in 50 microl) on peripheral mechanically-evoked responses of spinal neurones were studied in halothane-anaesthetised rats in vivo. Responses of spinal neurones to mechanical punctate stimulation (von Frey filaments, 8-80 g) of the peripheral receptive field were similar in non-inflamed rats and rats with hindpaw carrageenan-induced inflammation. Intraplantar injection of anandamide, but not vehicle, significantly (P<0.05) inhibited innocuous and noxious mechanically-evoked responses of spinal neurones in rats with hindpaw inflammation, but not in non-inflamed rats. Co-administration of the cannabinoid (2) (CB(2)) receptor antagonist, SR144528 (10 microg in 50 microl), but not the cannabinoid (1) (CB(1)) receptor antagonist, SR141716A (10 microg in 50 microl), significantly blocked inhibitory effects of anandamide on peripheral evoked neuronal responses in rats with hindpaw inflammation. This study demonstrates inhibitory effects of exogenous anandamide on mechanically-evoked responses under inflammatory conditions in vivo, which are mediated by peripheral CB(2) receptors.
Sokal
D M
DM
Queen's Medical Centre, School of Biomedical Sciences, E Floor Medical School, University of Nottingham, NG7 2UH, Nottingham, UK.
Elmes
S J R
SJ
Kendall
D A
DA
Chapman
V
V
D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D000818:Animals; D001095:Arachidonic Acids / Q000008:administration & dosage*; D063385:Cannabinoid Receptor Modulators; D002186:Cannabinoids / Q000008:administration & dosage*; D063388:Endocannabinoids; D006614:Hindlimb / Q000187:drug effects / Q000503:physiopathology; D007249:Inflammation / Q000139:chemically induced / Q000188:drug therapy / Q000503:physiopathology; D008297:Male; D010812:Physical Stimulation / Q000379:methods; D053284:Polyunsaturated Alkamides; D020671:Posterior Horn Cells / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D043885:Receptor, Cannabinoid, CB2; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug / Q000819:agonists / Q000037:antagonists & inhibitors / Q000502:physiology*
D018685:Anesthetics, Inhalation; D001095:Arachidonic Acids; D063385:Cannabinoid Receptor Modulators; D002186:Cannabinoids; C469526:Cnr2 protein, rat; D063388:Endocannabinoids; D053284:Polyunsaturated Alkamides; D043885:Receptor, Cannabinoid, CB2; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug; C078814:anandamide