The role of 5-hydroxytryptamine3 receptors in the vagal afferent activation-induced inhibition of the first cervical dorsal horn spinal neurons projected from tooth pulp in the rat.
To test the hypothesis that vagal afferent (VA) stimulation modulates the first cervical dorsal horn (C(1)) neuron activity, which is projected by tooth pulp (TP) afferent inputs through the activation of a local GABAergic mechanism via 5-hydroxytryptamine(3) (5-HT(3)) receptors, we used the technique of microiontophoretic application of drugs. In pentobarbital-anesthetized rats, we recorded C(1) spinal neuron activity responding to TP stimulation. The TP stimulation-evoked C(1) spinal neuron excitation was inhibited by VA stimulation, and this inhibition was significantly attenuated by iontophoretic application of the 5-HT(3) receptor antagonist ICS 205-930 (3-tropanyl-indole-3-carboxylate hydrochloride [endo-8-methyl-8-azabicyclo [3.2.1] oct-3-ol indol-3-yl-carboxylate hydrochloride]) (40 nA) or the GABA(A) receptor antagonist bicuculline (40 nA). In another series of experiments, we determined that 60 nA iontophoretic application of glutamate produced a maximal increase in the C(1) spinal neuron activity at a minimal current. In 53 of 65 neurons (81.5%), VA conditioning stimulation (1.0 mA x 0.1 ms, 50 Hz for 30 s) caused a significant inhibition (35.1%) of the glutamate (60 nA) application-evoked C(1) spinal neuron excitation. Iontophoretic application of ICS 205-930 (40 nA) or bicuculline (40 nA) significantly attenuated the VA stimulation-induced inhibition of glutamate iontophoretic application (60 nA)-evoked C(1) spinal neuron excitation. These results suggest that VA stimulation-induced suppression of C(1) spinal neuron activity, responding to TP stimulation, involve 5-HT(3) receptor activation, possibly originating in the descending serotonergic inhibitory system, and postsynaptic modulation of inhibitory GABAergic neurons.
Tanimoto
Takeshi
T
Department of Physiology, Nippon Dental University, School of Dentistry at Tokyo, 1-9-20 Fujimi, Chiyoda-ku, Tokyo 102-8159, Japan. ttt1224@tokyo.ndu.ac.jp
Takeda
Mamoru
M
Nishikawa
Toshimi
T
Matsumoto
Shigeji
S
D000344:Afferent Pathways / Q000187:drug effects / Q000502:physiology; D000818:Animals; D001016:Aortic Bodies / Q000187:drug effects / Q000502:physiology*; D003782:Dental Pulp / Q000166:cytology*; D004347:Drug Interactions; D004558:Electric Stimulation; D018698:Glutamic Acid / Q000494:pharmacology; D007211:Indoles / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D020671:Posterior Horn Cells; D051381:Rats; D044406:Receptors, Serotonin, 5-HT3 / Q000502:physiology*; D058831:Serotonin 5-HT3 Receptor Antagonists; D012702:Serotonin Antagonists / Q000494:pharmacology; D013131:Spine / Q000166:cytology*; D000077526:Tropisetron
D007211:Indoles; D044406:Receptors, Serotonin, 5-HT3; D058831:Serotonin 5-HT3 Receptor Antagonists; D012702:Serotonin Antagonists; D018698:Glutamic Acid; D000077526:Tropisetron