| Topical application of disodium isostearyl 2-O-L-ascorbyl phosphate, an amphiphilic ascorbic derivative, reduces neuropathic hyperalgesia in rats. | |
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MedLine Citation:
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PMID: 22229645 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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BACKGROUND AND PURPOSE Ca(v) 3.2 T-type calcium channels targeted by hydrogen sulfide (H(2) S) are involved in the neuropathic hyperalgesia in rats. Given evidence that ascorbic acid inhibits Ca(v) 3.2, we asked if intraplantar (i.pl.) administration of ascorbic acid or topical application of disodium isostearyl 2-O-L-ascorbyl phosphate (DI-VCP), a skin-permeable ascorbic derivative, reverses the hyperalgesia induced by NaHS, an H(2) S donor, and the neuropathic hyperalgesia EXPERIMENTAL APPROACH Mechanical hyperalgesia was evoked by i.pl. NaHS, and the neuropathic hyperalgesia was induced by L5 spinal nerve cutting (L5SNC) or by repeated administration of paclitaxel, an anti-cancer drug, in rats. Dermal ascorbic acid levels were determined by a colorimetric method. KEY RESULTS The NaHS-evoked, possibly Ca(v) 3.2-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. The 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 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 revered by topical DI-VCP ointment. CONCLUSIONS AND IMPLICATIONS Ascorbic acid, known to inhibit Ca(v) 3.2, functions to suppress the neuropathic hyperalgesia. DI-VCP ointment for topical application is considered to help in 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 Date: 2012-1-9 |
Journal Detail:
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Title: British journal of pharmacology Volume: - ISSN: 1476-5381 ISO Abbreviation: - Publication Date: 2012 Jan |
Date Detail:
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Created Date: 2012-1-10 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 7502536 Medline TA: Br J Pharmacol Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
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, Department of Food and Cosmetic Science, Faculty of Bioindustry, Tokyo University of Agriculture, Abashiri, Hokkaido, Japan, HBC Science Research Center Co., Ltd., Osaka, Japan. |
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