Inhibitory Effects of Valdecoxib on Sodium Currents in Sensory Neurons

J Korean Neurol Assoc > Volume 25(1); 2007 > Article

Journal of the Korean Neurological Association 2007;25(1): 81-91.

감각신경세포의 소디움 전류에 대한 valdecoxib의 억제효과

조정선, 김태훈a 신용규a 이정수a 박미정c 송진호a

중앙대학교 의과대학 약리학교실a, 서울보훈병원 신경과b, 서울산업대학교 안경광학과c

Inhibitory Effects of Valdecoxib on Sodium Currents in Sensory Neurons

Jeong Seon Cho

Department of Pharmacology, Chung-Ang University, College of Medicinea Department of Neurology, Seoul Veterans Hospitalb Department of Visual Optics, Seoul National University of Technologyc

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. KeyWords:Analgesia, Dorsal root ganglia, Patch-clamp, Sodium channel, Tetrodotoxin, Valdecoxib