Effect of Mexiletine on Vincristine-induced Painful Neuropathy in Mice.
From: Department of Pathophysiology and Therapeutics, School of Pharmacy and Pharmaceutical Sciences, Hoshi University, 4-41, Ebara 2-chome, Shinagawa-ku, Tokyo 142-8501, Japan. kamei@hoshi.ac.jp
European journal of pharmacology
- Publish Date: Apr 2006
- ISSN: 0014-2999
- Volume: 536
- Issue: 1-2
- Pages: 123-7
- Medium: Print
- Language: English
- Citation (JAMA): Kamei Junzo, Nozaki Chihiro, Saitoh Akiyoshi, et al. Effect of Mexiletine on Vincristine-induced Painful Neuropathy in Mice.. Eur. J. Pharmacol. Apr 2006;536:123-7
Abstract
In the present study, we examined the effect of mexiletine on vincristine-induced thermal hyperalgesia in mice. Mice were intraperitoneally treated with vincristine at a dose of 0.05 mg/kg one day after the measurement of the pre-drug latency in the tail-flick test, and then treated with a dose of 0.125 mg/kg twice a week for 6 weeks. In vincristine-treated mice, a significant decrease in tail-flick latency developed at 6 weeks after treatment. Pretreatment with mexiletine, at doses of 3, 10 and 30 mg/kg, i.p., dose-dependently increased the tail-flick latency in vincristine-treated mice. A significant reduction of the tail-flick latency was observed when the tail-flick latency was examined 60 min after i.t. administration of NG-nitro-L-arginine methyl ester (L-NAME, 30 nmol), a nitric oxide synthase (NOS) inhibitor, in naive mice. This L-NAME-induced thermal hyperalgesia was dose-dependently attenuated by pretreatment with mexiletine (10 and 30 mg/kg, i.p.), 10 min before the injection of L-NAME. The duration of nociceptive behavioral response induced by fenvalerate, at a dose of 0.1 microg, i.t., was significantly increased by pretreatment with L-NAME (30 nmol, i.t.). Intrathecal pretreatment with L-arginine (300 pmol) significantly reversed the L-NAME-induced enhancement of fenvalerate-induced nociceptive responses. The present study demonstrates that systemic mexiletine can effectively attenuate vincristine-induced thermal hyperalgesia. Furthermore, these results suggest that blockade of nitric oxide-induced enhancement of nociceptive transmission, in which tetrodotoxin-resistant sodium channels play an important role, may participate in the antinociceptive effect of mexiletine on vincristine-induced thermal hyperalgesia.
Mesh Headings (Keywords): Animals, Arginine, Behavior, Animal, Dose-Response Relationship, Drug, Drug Synergism, Enzyme Inhibitors, Hyperalgesia, Injections, Intraperitoneal, Injections, Spinal, Male, Mexiletine, Mice, Mice, Inbred ICR, NG-Nitroarginine Methyl Ester, Neuralgia, Nitric Oxide Synthase, Nitriles, Pain Measurement, Pyrethrins, Vincristine
Check for Full Text / PubMed Unique Identifier (PMID): 16556439
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