Abstract
Intrathecal administration of baclofen, a selective GABAB receptor agonist, is known to have an antinociceptive effect on various pain models. In the present study, we investigated effects of baclofen on modality-dependent excitatory synaptic responses of substantia gelatinosa (SG) neurons in the spinal dorsal horn using in vivo patch-clamp recording technique. Adult male Sprague-Dawley rats were anesthetized with urethane. After thoracolumbar laminectomy was performed, patch electrodes were inserted into the SG at the spinal level of L3-L5 and then whole-cell patch-clamp recordings were obtained from SG neurons. Under voltage-clamp conditions, SG neurons exhibited miniature EPSCs.Baclofen decreased the frequency but not amplitude of mEPSCs. Pinch and touch stimuli applied to the ipsilateral hindlimb evoked a barrage of large amplitude of EPSCs. Baclofen also inhibited the amplitude of large amplitude of EPSCs evoked by those stimuli in a dose-dependent manner. On the other hand, the frequency of large amplitude of EPSCs was not affected by baclofen. These inhibitory actions of baclofen were blocked in the presence of CGP55845, a selective antagonist of GABAB receptor. The present findings suggest that baclofen inhibits both noxious and innocuous mechanical excitatory transmission in the SG through activation of GABAB receptors on presynaptic terminals. This inhibition of mechanical inputs to the SG may be a possible mechanism for antinociception by baclofen. [J Physiol Sci. 2006;56 Suppl:S179]
