The purpose of the present study was to determine whether modulation of the trigeminal spinal nucleus oralis (TSNO) neurons related to tooth-pulp (TP)-evoked jaw-opening reflex (JOR) after electrical stimulation of the sciatic nerve (SN) is mediated by the descending serotonergic (5-HT3) inhibitory system activated by inhibitory GABAergic interneurons. In 30 anesthetized rats, the activity of TSNO neurons (87.5%, 35/40) and all digastric muscle electromyograms (dEMG, n = 30) in response to TP stimulation (at an intensity of 3.5 times the threshold for JOR) were inhibited by conditioning stimulation of the SN (5.0 mA x 0.5 ms, 1 Hz, conditioning-test intervals; 50 ms). The inhibitory effects were significantly attenuated after intravenous administration of the 5-HT3 receptor antagonist ICS 205-930 (n = 6). Using multilbarrel electrodes, iontophoretic application of ICS 205-930 into the TSNO significantly reduced the SN stimulation-induced inhibition of TP-evoked TSNO neuronal excitation (n = 6), and in the same neurons, iontophoretic application of the GABA(A) receptor antagonist bicuculline into the TSNO greatly inhibited their effect. On the other hand, we found the expression of 5-HT3 receptor immunoreactive neurons in the TSNO. These results suggest that SN stimulation may activate the descending serotonergic (5-HT3) inhibitory system through activation of inhibitory GABAergic interneurons, which inhibit excitatory responses of the TSNO neurons to TP stimulation. (C) 2004 Elsevier Inc. All rights reserved.