Junzo Kamei1,*, Mitsumasa Sasaki2, Ko Zushida1, Kayo Morita1 and Shun-ichi Tanaka3
1Department of Pathophysiology & Therapeutics, Faculty of Pharmaceutical Sciences, Hoshi University, Tokyo 142-8501, Japan
2Basic Research Laboratory, HALD Inc., Yokohama 236-0003, Japan
3Department of Neurobiology of Aging Laboratories, The Mount Sinai School of Medicine, New York, NY 10029-6574, USA
*Corresponding author. FAX: +81-3-5498-5029, E-mail: email@example.com
Abstract: The intrathecal injection of fenvalerate, a sodium channel activator, at doses of 0.01 to 3 mg, dose-dependently induced the duration of a characteristic behavioral syndrome mainly consisting of reciprocal hind limb scratching directed towards caudal parts of the body and biting or licking of the hind legs in mice. Fenvalerate-induced behavior was inhibited by morphine (1 - 10 mg/kg, i.p.). The characteristic behavior was also inhibited by mexiletine, a sodium channel blocker; MK-801, a N-methyl-D-aspartate ion-channel blocker; and GR82334, a neurokinin-1-receptor antagonist. Calphostin C (3 pmol, i.t.), a protein kinase C inhibitor, inhibited fenvalerate-induced behavior. On the other hand, phorbol-12, 13-dibutyrate (50 pmol, i.t.), a protein kinase C activator, markedly enhanced the fenvalerate-induced behavior. The present results also showed that fenvalerate produced thermal allodynia and hyperalgesia in the tail-flick test. Furthermore, fenvalerate-induced thermal allodynia and hyperalgesia were inhibited by the pretreatment with calphostin C. These results suggest that the intrathecal administration of fenvalerate induces a marked nociceptive response and thermal allodynia/hyperalgesia, and they suggest that tetrodotoxin-resistant sodium channels may play an important role in this effect.
Keywords: Allodynia, Hyperalgesia, Nociception, Fenvalerate, Tetrodotoxin-resistant sodium channel
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