SR 141716A, a cannabinoid receptor antagonist, produces hyperalgesia in untreated mice.
Antinociceptive effects of cannabinoids are well documented. However, the physiological role of endogenous cannabinoids in nociception is unknown. We evaluated the effects of the cannabinoid receptor antagonist SR 141716A (N-piperidino-5-(4-chlorophenyl)-1-(2, 4-dichlorophenyl)-4-methyl-3-pyrazolecarboxamide) on mouse hot plate latencies. Intrathecal injection of SR 141716A evoked a significant thermal hyperalgesia. These results suggest that the cannabinoid system tonically regulates thermal nociceptive thresholds. Furthermore, the absence of this regulation results in hyperalgesia suggesting that hypoactivity of this system may be involved in certain types of chronic pain.
Richardson
J D
JD
Department of Pharmacology, University of Minnesota, Minneapolis 55455, USA. jennelle@lenti.med.umn.edu
Aanonsen
L
L
Hargreaves
K M
KM
D000818:Animals; D002186:Cannabinoids / Q000037:antagonists & inhibitors*; D006930:Hyperalgesia / Q000139:chemically induced* / Q000503:physiopathology; D007278:Injections, Spinal; D008297:Male; D051379:Mice; D009119:Muscle Contraction / Q000187:drug effects; D010147:Pain Measurement / Q000187:drug effects; D017288:Pain Threshold / Q000187:drug effects; D010880:Piperidines / Q000008:administration & dosage / Q000494:pharmacology*; D011720:Pyrazoles / Q000008:administration & dosage / Q000494:pharmacology*; D011930:Reaction Time / Q000187:drug effects; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug / Q000037:antagonists & inhibitors*; D000077285:Rimonabant
D002186:Cannabinoids; D010880:Piperidines; D011720:Pyrazoles; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug; D000077285:Rimonabant