Cannabinoid modulation of dynorphin A: correlation to cannabinoid-induced antinociception

Intrathecal administration of anandamide, Delta(9)-tetrahydrocannabinol (THC) and(-)-3-[2-hydroxy-4-(1, 1-dimethyheptyl)ptyl)phenyl]-4(3-hydroxypropyl)-cicloexan-1-ol(CP55,930) induced spinal antinociception accompanied by differential kappa-opioid receptor involvement and dynorphin A peptide release. Antinociception using the tail-flick test was induced by the classical cannabinoid THC and was blocked totally by 17,17'-bis(cyclopropylmethyl)-6',6,7,7'-tetrahydro-4,5,4'5'-diepoxy-6,6'-(imino)[7,7'-bimorphinan]-3,3',14,14'-tetrol (norbinaltorphimine) indicating a significant and critical kappa-opioid receptor component. The endogenous cannabinoid, anandamide and the non-classical bicyclic cannabinoid, CP55,940, induced non-nor-BNI-sensitive effects. The N-piperidino-5-(4-chlorophenyl-1-(2,4-dichlorophenyl)-4-methyl-3-pyrazole-carboxamide (SR141716A)-mediated attenuation of spinal antinociception imparted by the various cannabinoids indicates cannabinoid CB1 receptor involvement. THC-induced an enhancement of immunoreactive dynorphin A release which coincided with the onset. but not duration antinociception. The release of dynorphin A was also attenuated by SR141716A suggesting it is cannabinoid CB1 receptor-mediated. These data indicate a critical role for dynorphin A release in the initiation of the antinociceptive effects of the cannabinoids at the spinal level. (C) 1999 Elsevier Science B.V. All rights reserved.