Abstract |
The aim of this study was to examine the involvement of 5-HT and 5-HT(2A) receptors in neuropathic pain and their possible cellular mechanism. To evaluate a potential therapy the 5-HT(2A) receptor antagonist ketanserin was administered topically or subcutaneously in rats with L5 nerve ligation. Unilateral spinal nerve ligation induced hypersensitivity to thermal and mechanical stimuli in the ipsilateral hindpaw and an increase in calcitonin gene-related peptide (CGRP) immunoreactivity (CGRP-IR) in small and medium diameter neurons in dorsal root ganglia (DRG) at L4 and L6, but not at L5. Topical application of ketanserin (3%) delivered in a mixture of gelatin, glycerol and kaolin onto skin over the hindpaw produced significant elevation of nociceptive threshold in the paw. Daily injection of ketanserin inhibited the thermal hyperalgesia in a dose dependent manner (0.1 and 0.3mg/kg, s.c.). The inhibition occurred at 1-3 days after the injection started and persisted for at least 2 weeks without decline. Injection of ketanserin (0.3mg/kg) also suppressed tactile allodynia. Moreover, ketanserin (0.3mg/kg) reversed the increase in CGRP-IR expression in L4 and L6 DRG neurons. These results support the hypothesis that adaptive change in CGRP expression that occurred in the DRG adjacent to the DRG containing injured neurons underlies the nerve ligation-induced hypersensitivity. This study suggests that 5-HT and 5-HT(2A) receptors contribute to the maintenance of neuropathic pain by up-regulating the expression of CGRP-IR, and that topical and systemic administrations of ketanserin are promising therapies for relieving neuropathic pain without tolerance.
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Authors | Dongmei Wang, Yun Gao, Haiming Ji, Yanguo Hong |
Journal | European journal of pharmacology
(Eur J Pharmacol)
Vol. 627
Issue 1-3
Pg. 124-30
(Feb 10 2010)
ISSN: 1879-0712 [Electronic] Netherlands |
PMID | 19913012
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | Copyright (c) 2009 Elsevier B.V. All rights reserved. |
Chemical References |
- Receptors, Serotonin
- Serotonin Antagonists
- Serotonin
- Ketanserin
- Calcitonin Gene-Related Peptide
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Topics |
- Administration, Topical
- Animals
- Calcitonin Gene-Related Peptide
(metabolism)
- Ganglia, Spinal
(drug effects, metabolism, pathology)
- Gene Expression Regulation
(drug effects)
- Hyperalgesia
(etiology, metabolism, psychology)
- Injections, Subcutaneous
- Ketanserin
(administration & dosage, pharmacology, therapeutic use)
- Ligation
- Male
- Neurons
(drug effects, metabolism)
- Pain
(drug therapy, etiology, metabolism, psychology)
- Perception
(drug effects)
- Rats
- Rats, Sprague-Dawley
- Receptors, Serotonin
(metabolism)
- Serotonin
(metabolism)
- Serotonin Antagonists
(administration & dosage, pharmacology, therapeutic use)
- Spinal Nerves
(drug effects, surgery)
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