| Ondansetron reverses antihypersensitivity from clonidine in rats after peripheral nerve injury: role of γ-aminobutyric acid in α2-adrenoceptor and 5-HT3 serotonin receptor analgesia. | |
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MedLine Citation:
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PMID: 22722575 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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INTRODUCTION: Monoaminergic pathways, impinging an α2-adrenoceptors and 5-HT3 serotonin receptors, modulate nociceptive transmission, but their mechanisms and interactions after neuropathic injury are unknown. Here we examine these interactions in rodents after nerve injury. METHODS: Male Sprague-Dawley rats following L5-L6 spinal nerve ligation (SNL) were used for either behavioral testing, in vivo microdialysis for γ-aminobutyric acid (GABA) and acetylcholine release, or synaptosome preparation for GABA release. RESULTS: Intrathecal administration of the α2-adrenoceptor agonist (clonidine) and 5-HT3 receptor agonist (chlorophenylbiguanide) reduced hypersensitivity in SNL rats via GABA receptor-mediated mechanisms. Clonidine increased GABA and acetylcholine release in vivo in the spinal cord of SNL rats but not in normal rats. Clonidine-induced spinal GABA release in SNL rats was blocked by α2-adrenergic and nicotinic cholinergic antagonists. The 5-HT3 receptor antagonist ondansetron decreased and chlorophenylbiguanide increased spinal GABA release in both normal and SNL rats. In synaptosomes from the spinal dorsal horn of SNL rats, presynaptic GABA release was increased by nicotinic agonists and decreased by muscarinic and α2-adrenergic agonists. Spinally administered ondansetron significantly reduced clonidine-induced antihypersensitivity and spinal GABA release in SNL rats. CONCLUSION: These results suggest that spinal GABA contributes to antihypersensitivity from intrathecal α2-adrenergic and 5-HT3 receptor agonists in the neuropathic pain state, that cholinergic neuroplasticity after nerve injury is critical for α2-adrenoceptor-mediated GABA release, and that blockade of spinal 5-HT3 receptors reduces α2-adrenoceptor-mediated antihypersensitivity via reducing total GABA release. |
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Authors:
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Ken-ichiro Hayashida; Masafumi Kimura; Masaru Yoshizumi; Shotaro Hobo; Hideaki Obata; James C Eisenach |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural |
Journal Detail:
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Title: Anesthesiology Volume: 117 ISSN: 1528-1175 ISO Abbreviation: Anesthesiology Publication Date: 2012 Aug |
Date Detail:
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Created Date: 2012-07-26 Completed Date: 2012-10-15 Revised Date: 2013-04-16 |
Medline Journal Info:
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Nlm Unique ID: 1300217 Medline TA: Anesthesiology Country: United States |
Other Details:
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Languages: eng Pagination: 389-98 Citation Subset: AIM; IM |
Affiliation:
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Wake Forest University School of Medicine, Winston Salem, NC, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Adrenergic alpha-2 Receptor Agonists
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pharmacology Analgesia / methods Animals Clonidine / pharmacology* Disease Models, Animal Male Ondansetron / pharmacology* Pain / drug therapy Pain Management / methods Peripheral Nerve Injuries* Rats Rats, Sprague-Dawley Receptors, Adrenergic, alpha-2 / drug effects* Receptors, Serotonin, 5-HT3 / drug effects* Serotonin Antagonists / pharmacology gamma-Aminobutyric Acid / pharmacology* |
| Grant Support | |
ID/Acronym/Agency:
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DA27690/DA/NIDA NIH HHS; NS57594/NS/NINDS NIH HHS; R01 DA027690/DA/NIDA NIH HHS; R01 NS057594/NS/NINDS NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Adrenergic alpha-2 Receptor Agonists; 0/Receptors, Adrenergic, alpha-2; 0/Receptors, Serotonin, 5-HT3; 0/Serotonin Antagonists; 4205-90-7/Clonidine; 56-12-2/gamma-Aminobutyric Acid; 99614-02-5/Ondansetron |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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