Effects of 5-hydroxytryptamine on substantia gelatinosa neurons of the trigeminal subnucleus caudalis in immature mice.
Serotonin (5-hydroxytryptamine, 5-HT) is involved in the descending modulation of nociceptive transmission in the spinal dorsal horn. The trigeminal subnucleus caudalis (Vc; medullary dorsal horn) processes nociceptive input from the orofacial region, and 5-HT-containing axons are numerous in the superficial layers of the Vc. This study examined the actions of 5-HT on the substantia gelatinosa (SG) neurons of the Vc, using gramicidin-perforated patch-clamp recording in brainstem slice preparations from immature mice. In order to clarify the possible mechanisms underlying 5-HT actions in the SG of the Vc, the direct membrane effects of 5-HT and effects of 5-HT receptor subtype agonists were examined. 5-HT induced a hyperpolarization in the majority (64/115, 56%) of the SG neurons tested. Thirty nine (34%) SG neurons showed no response, and 12 (10%) neurons responded with depolarization. The hyperpolarizing response to 5-HT was concentration-dependent (0.1-30 μM; n=7), not desensitized by repeated application (n=22), and significantly attenuated by Ba(2+) (K(+) channel blocker; n=8). The 5-HT-induced hyperpolarization was maintained in the presence of TTX (Na(+) channel blocker), CNQX (non-NMDA glutamate receptor antagonist), AP5 (NMDA glutamate receptor antagonist), picrotoxin (GABA(A) receptor antagonist), and strychnine (glycine receptor antagonist), indicating direct postsynaptic action of 5-HT on SG neurons (n=7). The 5-HT-induced hyperpolarizing effects were mimicked by 8-OH-DPAT (5-HT(1A) receptor agonist) and α-methyl-5-HT (5-HT(2) receptor agonist) and blocked by WAY-100635 (5-HT(1A) receptor antagonist) and ketanserin (5-HT(2) receptor antagonist). Single-cell RT-PCR also revealed the presence of mRNA for 5-HT(1A) and 5-HT(2C) subtypes in the SG neurons. These results suggest that 5-HT acts directly on SG neurons and 5-HT-induced hyperpolarization is mediated, in part, by 5-HT(1A) receptors and 5-HT(2) receptors, as well as by the activation of K(+) channels, indicating an important role for 5-HT in the modulation of orofacial nociceptive processing at the level of the SG of the Vc in mice.
Department of Oral Physiology and Institute of Oral Bioscience, School of Dentistry, Chonbuk National University, Jeonju, Jeonbuk, 561-756, Republic of Korea.
Hua
H
Yin
Seon Ah
SA
Park
Seong Kyu
SK
Han
Soo Joung
SJ
Park
D000818:Animals; D000831:Animals, Newborn; D005260:Female; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D051379:Mice; D008813:Mice, Inbred ICR; D009619:Nociceptors / Q000187:drug effects*; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012701:Serotonin / Q000494:pharmacology*; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*; D013376:Substantia Gelatinosa / Q000187:drug effects* / Q000378:metabolism; D014275:Trigeminal Caudal Nucleus / Q000187:drug effects* / Q000378:metabolism
D015221:Potassium Channels; D012333:RNA, Messenger; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D012701:Serotonin