Role of cannabinoids in regulating nociceptive transmission in the rat spinal dorsal horn

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Nociceptive information is transmitted through. primary-afferent AS and C fibers to the spinal dorsal horn, particularly the substantia gelatinosa (SG), where this transmission is modulated by a variety of endogenous substances including cannabinoids. This research project examined the effects of cannabinoids on excitatory (glutamatergic) and. inhibitory. (GABAergic and glycinergic) transmission by applying the blind whole-cell patch-clamp technique to SG neurons of adult rat spinal cord slices. The following results were obtained : (1) an endogenous cannabinoid anandamide (ANA ;0.01-10μM), another endogenous cannabinoid arachidonoyl glycerol (2-AG ;20μM) and cannabinoid receptor agonist WIN 55,212-2 (WIN-2;5-10μM) did not change holding currents ; (2) monosynaptically-evoked Aδ-and C-fiber excitatory postsynaptic currents (EPSCs) were reduced in amplitude by ANA (10μM), 2-AG (20μM) and WIN-2 (5μM), the former inhibition was larger in extent than the latter one ; (3) these cannabinoids … More did not affect the amplitude and frequency of spontaneous EPSCs ; (4) ANA reduced the amplitude of electrically-evoked inhibitory postsynaptic currents (IPSCs) in a concentration range of 1-5 μM ; (5) a similar inhibitory action was induced by 2-AG (20μM) and. WIN-2 (5μM) ; (6) the inhibitory action produced by ANA (10μM) was anatgonized by a cannabinoid-receptor anatgonist SR141716A (5μM) ; (7) ANA (10μM) increased a paired-pulse ratio of the evoked IPSC amplitudes ; (8) ANA (10μM) reduced the frequency of spontaneous IPSC without a change in the amplitude.In conclusion, cannabinoids inhibit in SG neurons monosynaptic glutamatergic excitatory transmission. from the periphery and also GABAergic and glycinergic inhibitory transmission, all of which are due to the activation of cannabinoid receptors located in nerve terminals. Considering the expression of CBI cannabinoid receptors in the spinal dorsal horn, these actions are mediated by CBI receptors. It is suggested that such a CB 1 receptor activation may contribute to at least a part of antinociception produced by intrathecal administration of cannabinoids. Less