OBJECTIVETo investigate the role of muscarinic cholinergic receptor (mAChR) subtypes in the regulation of glutamatergic input to the spinal dorsal horn neurons and the possible mechanism.

METHODSWhole-cell voltage-clamp recordings on acute spinal slice was utilized to investigate the effect of activation of mAChRs and blockade of M2/M4 subtypes on glutamatergic synaptic transmission in rat spinal dorsal horn neurons.

RESULTSThe nonselective mAChRs agonist oxotremorine-M concentration-dependently decreased the amplitude of monosynaptic and polysynaptic evoked glutamate-mediated excitatory postsynaptic currents (eEPSCs) in most of the neurons. The M2/M4 antagonist himbacine completely blocked the inhibitory effect of oxotremorine-M in 92.3% of monosynaptic and 75% of polysynaptic neurons in the spinal cord slices. In the remaining 16% neurons, himbacine partially blocked the inhibitory effect of oxotremorine-M.

CONCLUSIONSActivation of mAChRs in the spinal cord attenuates synaptic glutamate release to the dorsal horn neurons mainly through M2 and M4 receptor subtypes, indicating that a presynaptic inhibition in the spinal cord may be involved in the regulation of nociception by the cholinergic system and mAChRs.