Abstract | BACKGROUND AND PURPOSE: Although 5-HT(1B) receptors are expressed in trigeminal sensory neurons, it is still not known whether these receptors can modulate nociceptive transmission from primary afferents onto medullary dorsal horn neurons. EXPERIMENTAL APPROACH: Primary afferent-evoked EPSCs were recorded from medullary dorsal horn neurons of rat horizontal brain stem slices using a conventional whole-cell patch clamp technique under a voltage-clamp condition. KEY RESULTS: CP93129, a selective 5-HT(1B) receptor agonist, reversibly and concentration-dependently decreased the amplitude of glutamatergic EPSCs and increased the paired-pulse ratio. In addition, CP93129 reduced the frequency of spontaneous miniature EPSCs without affecting the current amplitude. The CP93129-induced inhibition of EPSCs was significantly occluded by GR55562, a 5-HT(1B/1D) receptor antagonist, but not LY310762, a 5-HT(1D) receptor antagonist. Sumatriptan, an anti- migraine drug, also decreased EPSC amplitude, and this effect was partially blocked by either GR55562 or LY310762. On the other hand, primary afferent-evoked EPSCs were mediated by the Ca(2+) influx passing through both presynaptic N-type and P/Q-type Ca(2+) channels. The CP93129-induced inhibition of EPSCs was significantly occluded by ω- conotoxin GVIA, an N-type Ca(2+) channel blocker. CONCLUSIONS AND IMPLICATIONS: The present results suggest that the activation of presynaptic 5-HT(1B) receptors reduces glutamate release from primary afferent terminals onto medullary dorsal horn neurons, and that 5-HT(1B) receptors could be, at the very least, a potential target for the treatment of pain from orofacial tissues.
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Authors | I-S Choi, J-H Cho, C-H An, J-K Jung, Y-K Hur, J-K Choi, I-S Jang |
Journal | British journal of pharmacology
(Br J Pharmacol)
Vol. 167
Issue 2
Pg. 356-67
(Sep 2012)
ISSN: 1476-5381 [Electronic] England |
PMID | 22462474
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | © 2012 The Authors. British Journal of Pharmacology © 2012 The British Pharmacological Society. |
Chemical References |
- Pyridines
- Pyrroles
- Receptor, Serotonin, 5-HT1B
- 3-(1,2,5,6-tetrahydropyrid-4-yl)pyrrolo(3,2-b)pyrid-5-one
- Glutamic Acid
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Topics |
- Action Potentials
- Afferent Pathways
(metabolism)
- Animals
- Electrophysiological Phenomena
- Glutamic Acid
(metabolism)
- Posterior Horn Cells
(physiology)
- Pyridines
(pharmacology)
- Pyrroles
(pharmacology)
- Rats
- Rats, Sprague-Dawley
- Receptor, Serotonin, 5-HT1B
(metabolism)
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