Cannabinoid CB1 receptors have been found in the superficial dorsal horn of the spinal cord, particularly the substantia gelatinosa (SG), which is thought to play a pivotal role in modulating nociceptive transmission. Although cannabinoids are known to inhibit excitatory transmission in SG neurons, their effects on inhibitory transmission have not yet been examined fully. In order to know further about a role of cannabinoids in regulating nociceptive transmission, we examined the effects of cannabinoids on inhibitory transmissions in adult rat SG neurons using whole-cell voltage-clamp recordings. Anandamide (10 μM) superfused for 2 min reduced glycinergic and GABAergic electrically-evoked inhibitory postsynaptic current (IPSC) amplitudes;these actions persisted for more than 6 min after washout. Similar actions were produced by cannabinoid-receptor agonist WIN55,212-2 (5 μM) and 2-arachidonoyl glycerol (20 μM). The evoked IPSC amplitudes reduced by anandamide recovered to the control level following superfusion of CB1-receptor antagonist SR141716A (5 μM). A ratio of the second to first evoked IPSC amplitude in paired-pulse experiments was increased by anandamide (10 μM). The frequencies of glycinergic and GABAergic spontaneous IPSCs were reduced by anandamide (10 μM) without a change in their amplitudes. It is concluded that cannabinoids depress inhibitory transmissions in adult rat SG neurons by activating CB1 receptors in nerve terminals. This action could contribute to the modulation of nociceptive transmission by cannabinoids.
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