Last data updates: 06 January 2011
Liu, F.Y., Xing, G.G., Qu, X.X., Xu, I.S., Han, J.S. and Wan, Y. (2007), 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. Journal of Pharmacology and
Experimental Therapeutics, 321 (3), 1046-1053.
Document type: Article Language: English Cited references: 34 Time cited: 15 Times self cited: 3
Abstract: 5-Hydroxytryptamine ( 5-HT; serotonin) plays an important role in the descending control
of nociception. 5-HT and its receptors have been extensively studied in the modulation of
nociceptive transmission at the spinal level using behavioral tests that may be affected by the effects
of 5-HT on motor performance and skin temperature. Using electrophysiological methods, the
present study aimed to systematically investigate the roles of 5-HT receptor subtypes on the
inhibitory effects of 5-HT on responses of the spinal wide dynamic range ( WDR) neurons to
C-fiber inputs in rats. Under basal conditions, topical application of 5-HT to the spinal cord
inhibited the C-fiber responses of WDR neurons dose-dependently, whereas antagonists of 5-HT1A
[ WAY 100635 [ N-[ 2-[ 4( 2-methoxyphenyl)-1-piperazinyl]
ethyl]-N-2-pyridinyl-cyclohexanecarboxamide maleate salt]], 5-HT1B [GR 55562
[ 3-[ 3-( dimethylamino) propyl]-4-hydroxy-N-[ 4-(4- pyrid-dinyl) phenyl] benzamide
dihydrochloride]], 5-HT2A [ ketanserin [ 3-[ 2-[ 4-( fluorobenzoyl)-1-piperidinyl] ethyl]-2,4[ 1H,
3H]-quinazolinedione tartrate]], 5-HT2C [ RS 102221
[ 8-[ 5-( 2,4-dimethoxy-5-(4-trifluoromethylphenylsulfonamido)
phenyl-5-oxopentyl]-1,3,8-triazaspiro[ 4.5] decane-2,4-dione hydrochloride]], 5-HT3 [ MDL 72222
[ 3-tropanyl-3,5dichlorobenzoate]], and 5-HT4 [ GR 113808 ([ 1-[ 2-[( methylsulfonyl)amino]
ethyl]-4-piperidinyl] methyl 1-methyl-1H-indole-3-carboxylate)] had no effect on their own. The
inhibitory effects of 5- HT were reversed by antagonists of 5-HT1B ( GR 55562), 5-HT2A
( ketanserin), 5-HT2C ( RS 102221), 5-HT3 ( MDL 72222), and 5-HT4 ( GR 113808) but not by
5-HT1A ( WAY 100635) receptor antagonists. Topical administration of agonists of 5-HT1A
[( 2R)-( +)-8-hydroxy-2-(di-n-propylamino) tetralin hydrobromide], 5-HT1B [ CGS 12066
[ 7-trifluoromethyl-4-( 4-methyl-1-piperazinyl) pyrrolo[ 1,2- a] quinoxaline maleate salt]], 5-HT2A
( alpha-methyl-5-hydroxytryptamine maleate), 5-HT2C [ MK 212 [ 6-chloro-2-( 1- piperazinyl)
pyrazine hydrochloride]], 5-HT3 [ 1-( 3-chlorophenyl) biguanide hydrochloride], and 5-HT4
[ 2-[ 1-( 4- piperonyl) piperazinyl] benzothiazole] also inhibited the C-responses. These results
suggest that, under basal conditions, there is no tonic serotonergic inhibition on the C-responses of
dorsal horn neurons, and multiple 5-HT receptor subtypes including 1B, 2A, 2C, 3, and 4 may be
involved in mediating the inhibitory effects of 5- HT.
Keywords Plus: Tail-Skin Temperature; Evoked-Responses; Flick Response; Nerve Ligation; Gaba
Release; Serotonin; Antinociception; Agonists; Pain; Cord
Reprint Address: Wan, Y (reprint author), Peking Univ, Neurosci Res Inst, Minist Educ, Key Lab
Neurosci, 38 Xue Yuan Rd, Beijing 100083, Peoples R China
Addresses:
1. Peking Univ, Neurosci Res Inst, Minist Educ, Key Lab Neurosci, Beijing 100083, Peoples R
China
2. Peking Univ, Dept Neurobiol, Minist Educ, Key Lab Neurosci, Beijing 100083, Peoples R China
E-mail Addresses: ywan@bjmu.edu.cn
1.
Seyrek, M., Kahraman, S., Deveci, M.S., Yesilyurt, O. and Dogrul, A. (2010), Systemic
cannabinoids produce CB1-mediated antinociception by activation of descending serotonergic
pathways that act upon spinal 5-HT7 and 5-HT2A receptors. European Journal of
2.
Pharmacology, 649 (1-3), 183-194.
Aira, Z., Buesa, I., Salgueiro, M., Bilbao, J., Aguilera, L., Zimmermann, M. and Azkue, J.J.
(2010), Subtype-specific changes in 5-HT receptor-mediated modulation of C Fibre-Evoked
3.
spinal field potentials are triggered by peripheral nerve injury. Neuroscience, 168 (3), 831-841.
Liu, F.Y., Qu, X.X., Ding, X., Cai, J., Jiang, H., Wan, Y., Han, J.S. and Xing, G.G. (2010),
Decrease in the descending inhibitory 5-HT system in rats with spinal nerve ligation. Brain
4.
Research, 1330, 45-60.
Silveira, J.W.S., Dias, Q.M., Del Bel, E.A. and Prado, W.A. (2010), Serotonin receptors are
involved in the spinal mediation of descending facilitation of surgical incision-induced
5.
increase of Fos-like immunoreactivity in rats. Molecular Pain, 6, Article Number: 17.
Jongen, J.L.M., Pederzani, T., Koekkoek, S.K., Shapiro, J., van der Burg, J., De Zeeuw, C.I.,
Huygen, F.J. and Holstege, J.C. (2010), Autofluorescent flavoprotein imaging of spinal
6.
nociceptive activity. Journal of Neuroscience, 30 (11), 4081-4087.
Granados-Soto, V., Arguelles, C.F., Rocha-Gonzalez, H.I., Godinez-Chaparro, B.,
Flores-Murrieta, F.J. and Villalon, C.M. (2010), The Role of peripheral 5-HT1A, 5-HT1B,
5-HT1D, 5-HT1E and 5-HT1F serotonergic receptors in the reduction of nociception in rats.
7.
Neuroscience, 165 (2), 561-568.
Bai, L.J., Qin, W., Liang, J.M., Tian, J. and Liu, Y.J. (2009), Spatiotemporal Modulation of
Central Neural Pathway Underlying Acupuncture Action: A Systematic Review. Current
8.
Medical Imaging Reviews, 5 (3), 167-173.
Castaneda-Corral, G., Rocha-Gonzalez, H.I., raiza-Saldana, C.I., mbriz-Tututi, M.,
Vidal-Cantu, G.C. and Granados-Soto, V. (2009), Role of Peripheral and Spinal 5-Ht6
9.
Receptors According to the Rat Formalin Test. Neuroscience, 162 (2), 444-452.
Guenther, U., Manzke, T., Wrigge, H., Utschmann, M., Zinserling, J., Putensen, C. and Hoeft,
A. (2009), The Counteraction of Opioid-Induced Ventilatory Depression by the Serotonin
1A-Agonist 8-OH-DPAT Does Not Antagonize Antinociception in Rats In Situ and In Vivo.
Anesthesia and Analgesia, 108 (4), 1169-1176.
10. Qu, X.X., Cai, J., Li, M.J., Chi, Y.N., Liao, F.F., Liu, F.Y., Wan, Y., Han, J.S. and Xing, G.G.
(2009), Role of the spinal cord NR2B-containing NMDA receptors in the development of
neuropathic pain. Experimental Neurology, 215 (2), 298-307.
11. Guo, M., Chen, S. and Liu, X.M. (2008), Material basis for inhibition of Dragon's Blood on
evoked discharges of wide dynamic range neurons in spinal dorsal horn of rats. Science in
China Series C-Life Sciences, 51 (11), 1025-1038.
12. Luo, F. and Wang, J.Y. (2008), Modulation of central nociceptive coding by acupoint
stimulation. Neurochemical Research, 33 (10), 1950-1955.
13. Zhao, Z.Q. (2008), Neural mechanism underlying acupuncture analgesia. Progress in
Neurobiology, 85 (4), 355-375.
14. Gerin, C., Teilhac, J.R., Smith, K. and Privat, A. (2008), Motor activity induces release of
serotonin in the dorsal horn of the rat lumbar spinal cord. Neuroscience Letters, 436 (2), 91-95.
15. Yu, A.C.H., Wan, Y., Chui, D.H., Cui, C.L., Luo, F., Wang, K.W., Wang, X.M., Wang, Y.,
Wu, L.Z., Xing, G.G. and Han, J.S. (2008), The Neuroscience Research Institute at Peking
University: A place for the solution of pain and drug abuse. Cellular and Molecular
Neurobiology, 28 (1), 13-19.