Cannabinoid actions on rat superficial medullary dorsal horn neurons in vitro

1. This study examined the cellular actions of cannabinoids on neurons in the substantia gelatinosa of the spinal trigeminal nucleus pars caudalis, using whole-cell and perforated patch recording in brain slices. 2. The cannabinoid agonist WIN55,212-2 (3 microM) decreased the amplitude of both GABAergic and glycinergic electrically evoked inhibitory postsynaptic currents (IPSCs) by 35 and 41 %, respectively. This inhibition was completely reversed by the CB(1) receptor-selective antagonist N-piperidino-5-(4-chlorophenyl)-l-(2,4-dichlorophenyl)-4-methyl-3-pyrazole-carboxamide) (SR141716A, 3 microM). WIN55,212-2 also produced relative facilitation of the second evoked IPSC to paired stimuli. 3. WIN55,212-2 decreased the rate of both GABAergic and glycinergic miniature IPSCs by 44 and 34 %, respectively, without changing their amplitude distributions 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 significant 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 neurotransmission. At the cellular level, the analgesic action of cannabinoids on these medullary dorsal horn neurons therefore differs from that of mu-opioids, which have both pre- and postsynaptic actions.