Presynaptic inhibition by baclofen of miniature EPSCs and IPSCs in substantia gelatinosa neurons of the adult rat spinal dorsal horn

Intrathecal administration of baclofen, a GABAB-receptor agonist, affects p ain behavior induced by formalin in a biphasic manner; baclofen at low dose s enhances pain while producing antinociception at high doses. This may be due to the fact that baclofen modulates each of excitatory and inhibitory t ransmission in the dorsal horn of the spinal cord with a distinct sensitivi ty, resulting in a biphasic action on pain transmission. To address this is sue, we examined the actions of baclofen on miniature excitatory (glutamate rgic) and inhibitory (GABAergic) postsynaptic currents (mEPSCs and mIPSCs, respectively) in substantia gelatinosa (SG) neurons of adult rat spinal cor d slices by using the whole-cell voltage-clamp technique. Baclofen reduced the frequency of both mEPSC and mIPSC without a change in their amplitudes. These actions were dose-dependent in a concentration range of 0.1-100 mu M ; the effective concentrations for the half-inhibition of mEPSC and mIPSC f requency were 4.44 +/- 0.60 mu M (n = 7) and 4.31 +/- 0.77 mu M (n = 6), re spectively. These results indicate that each of glutamatergic and GABAergic nerve terminals in the SG is endowed with the GABAB receptor, the activati on of which depresses the release of neurotransmitter from the terminal; th is provides a cellular basis for the modulation of pain by baclofen. It is suggested from a similar affinity for baclofen of the GABAB receptors on bo th terminals that the baclofen-induced biphasic action on pain behaviors ca nnot be accounted for by only its presynaptic actions in the SG and that ot her actions such as an inhibitory action of baclofen on postsynaptic neuron s also have to be taken into consideration. (C) 2000 International Associat ion for the Study of Pain. Published by Elsevier Science B.V. All rights re served.