Cannabinoid actions on rat superficial medullary dorsal horn neurons in vitro

1. This study examined the cellular actions of cannabinoids on neurons in t he substantia gelatinosa of the spinal trigeminal nucleus bars caudalis, us ing whole-cell and perforated hatch recording in brain slices. 2. The cannabinoid agonist WIN55,212-2 (3 muM) decreased the amplitude of b oth GABAergic and glycinergic electrically evoked inhibitory postsynaptic c urrents (IPSCs) by 35 and 41%, respectively. This inhibition was completely reversed by the CB, receptor-selective antagonist N-piperidino-5-(4-chloro phenyl)-1-(2,4-dichlorophenyl)-4-methyl-3-pyrazole-carboxamide) (SR141716A, 3 muM). WIN55,212-2 also produced relative facilitation of the second evok ed IPSO to paired stimuli. 3. WIN55,212-2 decreased the rate of both GABAergic and glycinergic miniatu re IPSCs by 44 and 34%, respectively, without changing their amplitude dist ributions or kinetics. 4. WIN55,212-2 did not affect the amplitude of electrically evoked non-NMDA glutamatergic excitatory postsynaptic currents (EPSCs). 5. WIN55,212-2 produced no postsynaptic membrane current. and had no signif icant effect on membrane conductance over a range of membrane potentials (- 60 to -130 mV). 6. These results suggest that, within the superficial medullary dorsal horn , cannabinoids presynaptically inhibit GABAergic and glycinergic neurotrans mission. At the cellular level, the analgesic action of cannabinoids on the se medullary dorsal horn neurons therefore differs from that, of,mu -opioid s, which have both pre- and postsynaptic actions.