 |
Next Article 
Journal of Neuroscience, Vol 11, 1881-1888, Copyright © 1991 by Society for Neuroscience
Spinal 5-HT3 receptor-mediated antinociception: possible release of GABA
AA Alhaider, SZ Lei and GL Wilcox
Department of Pharmacology, University of Minnesota, Minneapolis 55455.
Although 5-HT is clearly involved in spinal analgesia, its mode of action
remains obscure, perhaps because it has multiple and often opposing effects
mediated by its multiple receptor subtypes. This investigation uses
selective agonists and antagonists directed at the most recently defined
class of 5-HT receptors (5-HT3 receptors) in behavioral and
electrophysiological studies of nociception in the spinal cord of rodents.
The results demonstrate uniformly inhibitory effects of a selective 5-HT3
agonist on responses to noxious stimuli. Intrathecally administered
2-methyl 5-HT produced dose-dependent antinociception in the tail-flick
test and inhibited behaviors elicited by intrathecally administered
agonists for excitatory amino acid and neurokinin receptors, namely NMDA
and substance P (SP). All 20 dorsal horn neurons we examined, which
projected to the brain and responded to both noxious stimuli and NMDA, were
inhibited in a current-related manner by this 5-HT3 agonist applied
iontophoretically. Both the behavioral and electrophysiological effects
were blocked not only by the 5-HT3 antagonists zacopride and ICS 205-930,
but also by antagonists to the inhibitory amino acid GABA. Therefore, 5-HT
via an action at 5-HT3 receptors may evoked release of GABA, which may in
turn inhibit nociceptive transmission at a site postsynaptic to terminals
of primary afferent fibers. If the descending serotonergic analgesic system
in humans operates similarly, understanding it may enable the development
of new nonopioid, nonaddictive analgesics.
This article has been cited by other articles:
|
|
|
|
 
R. C. Drisdel, D. Sharp, T. Henderson, T. G. Hales, and W. N. Green
High Affinity Binding of Epibatidine to Serotonin Type 3 Receptors
J. Biol. Chem.,
April 11, 2008;
283(15):
9659 - 9665.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
F.-Y. Liu, G.-G. Xing, X.-X. Qu, I. S. Xu, J.-S. Han, and Y. Wan
Roles of 5-Hydroxytryptamine (5-HT) Receptor Subtypes in the Inhibitory Effects of 5-HT on C-Fiber Responses of Spinal Wide Dynamic Range Neurons in Rats
J. Pharmacol. Exp. Ther.,
June 1, 2007;
321(3):
1046 - 1053.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. Rusch, B. Musset, H. Wulf, A. Schuster, and D. E. Raines
Subunit-Dependent Modulation of the 5-Hydroxytryptamine Type 3 Receptor Open-Close Equilibrium by n-Alcohols
J. Pharmacol. Exp. Ther.,
June 1, 2007;
321(3):
1069 - 1074.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. A. Scott, M. Wood, and P. Flood
The pronociceptive effect of ondansetron in the setting of p-glycoprotein inhibition.
Anesth. Analg.,
September 1, 2006;
103(3):
742 - 746.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. Kato, T. Yasaka, T. Katafuchi, H. Furue, M. Mizuno, Y. Iwamoto, and M. Yoshimura
Direct GABAergic and Glycinergic Inhibition of the Substantia Gelatinosa from the Rostral Ventromedial Medulla Revealed by In Vivo Patch-Clamp Analysis in Rats
J. Neurosci.,
February 8, 2006;
26(6):
1787 - 1794.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. Stevens, D. Rusch, K. Solt, D. E. Raines, and P. A. Davies
Modulation of Human 5-Hydroxytryptamine Type 3AB Receptors by Volatile Anesthetics and n-Alcohols
J. Pharmacol. Exp. Ther.,
July 1, 2005;
314(1):
338 - 345.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Fassoulaki, A. Melemeni, M. Zotou, and C. Sarantopoulos
Systemic Ondansetron Antagonizes the Sensory Block Produced by Intrathecal Lidocaine
Anesth. Analg.,
June 1, 2005;
100(6):
1817 - 1821.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. Tanimoto, M. Takeda, T. Nishikawa, and S. Matsumoto
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
J. Pharmacol. Exp. Ther.,
November 1, 2004;
311(2):
803 - 810.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Bhattacharya, H. Dang, Q.-M. Zhu, B. Schnegelsberg, N. Rozengurt, G. Cain, R. Prantil, D. A. Vorp, N. Guy, D. Julius, et al.
Uropathic Observations in Mice Expressing a Constitutively Active Point Mutation in the 5-HT3A Receptor Subunit
J. Neurosci.,
June 16, 2004;
24(24):
5537 - 5548.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Morales and S.-D. Wang
Differential Composition of 5-Hydroxytryptamine3 Receptors Synthesized in the Rat CNS and Peripheral Nervous System
J. Neurosci.,
August 1, 2002;
22(15):
6732 - 6741.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. Arcioni, M. della Rocca, S. Romano, R. Romano, P. Pietropaoli, and A. Gasparetto
Ondansetron Inhibits the Analgesic Effects of Tramadol: A Possible 5-HT3 Spinal Receptor Involvement in Acute Pain in Humans
Anesth. Analg.,
June 1, 2002;
94(6):
1553 - 1557.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Panicker, H. Cruz, C. Arrabit, and P. A. Slesinger
Evidence for a Centrally Located Gate in the Pore of a Serotonin-Gated Ion Channel
J. Neurosci.,
March 1, 2002;
22(5):
1629 - 1639.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. P. Zeitz, N. Guy, A. B. Malmberg, S. Dirajlal, W. J. Martin, L. Sun, D. W. Bonhaus, C. L. Stucky, D. Julius, and A. I. Basbaum
The 5-HT3 Subtype of Serotonin Receptor Contributes to Nociceptive Processing via a Novel Subset of Myelinated and Unmyelinated Nociceptors
J. Neurosci.,
February 1, 2002;
22(3):
1010 - 1019.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. M. Garraway and S. Hochman
Serotonin Increases the Incidence of Primary Afferent-Evoked Long-Term Depression in Rat Deep Dorsal Horn Neurons
J Neurophysiol,
May 1, 2001;
85(5):
1864 - 1872.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. L. De Witte, B. Schoenmaekers, D. I. Sessler, and T. Deloof
The Analgesic Efficacy of Tramadol is Impaired by Concurrent Administration of Ondansetron
Anesth. Analg.,
May 1, 2001;
92(5):
1319 - 1321.
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Cui, Y. Feng, D. J. McAdoo, and W. D. Willis
Periaqueductal Gray Stimulation-Induced Inhibition of Nociceptive Dorsal Horn Neurons in Rats Is Associated with the Release of Norepinephrine, Serotonin, and Amino Acids
J. Pharmacol. Exp. Ther.,
May 1, 1999;
289(2):
868 - 876.
[Abstract]
[Full Text]
|
|
|
|
|
|
|
M. Kaneko and D. L. Hammond
Role of Spinal gamma -Aminobutyric AcidA Receptors in Formalin-Induced Nociception in the Rat
J. Pharmacol. Exp. Ther.,
August 1, 1997;
282(2):
928 - 938.
[Abstract]
[Full Text]
|
|
|
|
