Inhibitory Effects of Valdecoxib on Sodium Currents in Sensory Neurons.
- Author:
Jeong Seon CHO
1
;
Tae Hoon KIM
;
Yong Kyoo SHIN
;
Chung Soo LEE
;
Mijung PARK
;
Jin Ho SONG
Author Information
1. Department of Pharmacology, Chung-Ang University, College of Medicine, Korea. jinhos@cau.ac.kr
- Publication Type:Original Article
- Keywords:
Analgesia;
Dorsal root ganglia;
Patch-clamp;
Sodium channel;
Tetrodotoxin;
Valdecoxib
- MeSH:
Analgesia;
Animals;
Arthritis, Rheumatoid;
Cyclooxygenase 2;
Diagnosis-Related Groups;
Dysmenorrhea;
Female;
Ganglia, Spinal;
Kinetics;
Neurons;
Osteoarthritis;
Pain, Postoperative;
Patch-Clamp Techniques;
Rats;
Sensory Receptor Cells*;
Sodium Channels;
Sodium*;
Tetrodotoxin
- From:Journal of the Korean Neurological Association
2007;25(1):81-91
- CountryRepublic of Korea
- Language:Korean
-
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.
