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J Korean Neurol Assoc. 2007 Feb;25(1):81-91. Korean. Original Article.
Cho JS , Kim TH , Shin YK , Lee CS , Park M , Song JH .
Department of Pharmacology, Chung-Ang University, College of Medicine, Korea. jinhos@cau.ac.kr
Department of Neurology, Seoul Veterans Hospital, Korea.
Department of Visual Optics, Seoul National University of Technology, Korea.
Abstract

BACKGROUND: Valdecoxib is a selective cyclooxygenase-2 (COX-2) inhibitor. It is effective in the treatment of rheumatoid arthritis, osteoarthritis, primary dysmenorrhea, and postoperative pain. Two kinds of sodium currents, tetrodotoxin-sensitive (TTX-S) and tetrodotoxin-resistant (TTX-R), are expressed in the dorsal root ganglia (DRG). Both sodium currents are implicated in the formation of normal and abnormal pain. METHODS: The effects of valdecoxib on sodium currents in rat DRG neurons were investigated using the whole-cell variation of the patch-clamp technique. RESULTS: Valdecoxib suppressed two types of sodium currents in a dose-dependent manner, without altering the activation and inactivation kinetics of either current type. It shifted the activation voltage toward a depolarizing direction and the steady-state inactivation voltage toward a hyperpolarizing direction, and suppressed resting channels to similar extents in both types of sodium currents. Valdecoxib slowed the recovery of both sodium currents from inactivation, and suppressed them in a frequency-dependent manner. CONCLUSIONS: The results suggest that valdecoxib may produce analgesic effects through the inhibition of sodium currents in sensory neurons as well as COX-2.

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