抄録
Marijuana (Cannabis sativa) has a large variety of therapeutic effects including analgesia, all of which are thought to be due to an action of its primary active constituent, ∆9-tetrahydrocannabinol, acting on cannabinoid receptors. Endocannabinoids such as N-arachidonoylethanolamide (anandamide) are also known to exert antinociceptive activity in various animal models of acute pain. A subtype of cannabinoid receptors, CB1, is predominantly expressed in the CNS including the spinal superficial dorsal horn. Although a number of studies have examined an action of cannabinoids on synaptic transmission in the CNS, this is not understood fully in the spinal dorsal horn. In order to know a role of cannabinoids in regulating pain transmission, we studied the effects of anandamide and a synthetic cannabinoid-receptor agonist, WIN-55212-2, on excitatory and inhibitory transmission in substantia gelatinosa (SG) neurons of adult rat spinal cord slices by using the blind whole-cell patch-clamp technique. In many of the cells examined, anandamide (10 µM) attenuated the amplitude of either monosynaptic glutamatergic EPSCs through Aδ and C primary-afferent fibers, γ-aminobutyric acid (GABA) or glycine-mediated focally-evoked IPSCs. Spontaneous GABAergic and glycinergic IPSCs were inhibited in frequency but not amplitude by anandamide, while spontaneous EPSCs were unaffected in amplitude and frequency. These actions were mimicked by WIN-55212-2 (5 µM). It is concluded in SG neurons that can nabinoids inhibit the release of L-glutamate from primary-afferent central terminals and also the release of GABA and glycine from interneuron terminals, all of which are possibly due to the activation of the CB1 receptor; these actions would contribute to a modulation of nociceptive transmission to the spinal dorsal horn from the periphery.
