| Topical application of disodium isostearyl 2-O-L-ascorbyl phosphate, an amphiphilic ascorbic acid derivative, reduces neuropathic hyperalgesia in rats. | |
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MedLine Citation:
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PMID: 22229645 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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BACKGROUND AND PURPOSE: Ca(v) 3.2 T-type calcium channels, targeted by H(2) S, are involved in neuropathic hyperalgesia in rats and ascorbic acid inhibits Ca(v) 3.2 channels. Therefore, we evaluated the effects of intraplantar (i.pl.) administration of ascorbic acid or topical application of disodium isostearyl 2-O-L-ascorbyl phosphate (DI-VCP), a skin-permeable ascorbate derivative on hyperalgesia induced by NaHS, an H(2) S donor, and on neuropathic hyperalgesia. EXPERIMENTAL APPROACH: In rats mechanical hyperalgesia was evoked by i.pl. NaHS, and neuropathic hyperalgesia was induced by L5 spinal nerve cutting (L5SNC) or by repeated administration of paclitaxel, an anti-cancer drug. Dermal ascorbic acid levels were determined colorimetrically. KEY RESULTS: The NaHS-evoked Ca(v) 3.2 channel-dependent hyperalgesia was inhibited by co-administered ascorbic acid. Topical application of DI-VCP, but not ascorbic acid, prevented the NaHS-evoked hyperalgesia, and also increased dermal ascorbic acid levels. Neuropathic hyperalgesia induced by L5SNC or paclitaxel was reversed by i.pl. NNC 55-0396, a selective T-type calcium channel blocker, ascorbic acid or DI-VCP, and by topical DI-VCP, but not by topical ascorbic acid. The effects of i.pl. ascorbic acid and topical DI-VCP in the paclitaxel-treated rats were characterized by the faster onset and greater magnitude, compared with their effects in the L5SNC rats. Dermal ascorbic acid levels in the hindpaw significantly decreased after paclitaxel treatment, but not L5SNC, which was reversed by topical DI-VCP. CONCLUSIONS AND IMPLICATIONS: Ascorbic acid, known to inhibit Ca(v) 3.2 channels, suppressed neuropathic hyperalgesia. DI-VCP ointment for topical application may be of benefit in the treatment of neuropathic pain. |
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Authors:
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Kazumasa Okubo; Hiroki Nakanishi; Maho Matsunami; Hiroharu Shibayama; Atsufumi Kawabata |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: British journal of pharmacology Volume: 166 ISSN: 1476-5381 ISO Abbreviation: Br. J. Pharmacol. Publication Date: 2012 Jun |
Date Detail:
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Created Date: 2012-05-09 Completed Date: 2012-10-10 Revised Date: 2013-04-16 |
Medline Journal Info:
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Nlm Unique ID: 7502536 Medline TA: Br J Pharmacol Country: England |
Other Details:
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Languages: eng Pagination: 1058-68 Citation Subset: IM |
Copyright Information:
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© 2012 The Authors. British Journal of Pharmacology © 2012 The British Pharmacological Society. |
Affiliation:
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Division of Pharmacology and Pathophysiology, Kinki University School of Pharmacy, Higashi-Osaka, Japan. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Administration, Topical Animals Ascorbic Acid / administration & dosage, analogs & derivatives*, pharmacokinetics, therapeutic use Calcium Channel Blockers / administration & dosage, pharmacokinetics, therapeutic use* Calcium Channels, R-Type Cation Transport Proteins / antagonists & inhibitors* Disease Models, Animal Hyperalgesia / etiology, metabolism, prevention & control* Male Neuralgia / complications, drug therapy*, metabolism Ointments Pain Threshold / drug effects Patch-Clamp Techniques Rats Rats, Wistar Sensory Receptor Cells / drug effects, metabolism Skin / metabolism Skin Absorption |
| Chemical | |
Reg. No./Substance:
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0/Cacna1e protein, rat; 0/Calcium Channel Blockers; 0/Calcium Channels, R-Type; 0/Cation Transport Proteins; 0/Ointments; 50-81-7/Ascorbic Acid; 5EN0DE4P7X/disodium isostearyl 2-O-L-ascorbyl phosphate |
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