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KMID : 0359720070250010081
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Journal of the Korean Neurological Association
2007 Volume.25 No. 1 p.81 ~ p.91
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Inhibitory Effects of Valdecoxib on Sodium Currents in Sensory Neurons
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Cho Jeong-Seon
Kim Tae-Hoon
Shin Yong-Kyoo
Lee Chung-Soo
Park Mi-Jung
Song Jin-Ho
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Abstract
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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.
Conclusion: 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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KEYWORD
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Analgesia, Dorsal root ganglia, Patch-clamp, Sodium channel, Tetrodotoxin, Valdecoxib
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