J Korean Neurol Assoc.  2007 Feb;25(1):81-91.

Inhibitory Effects of Valdecoxib on Sodium Currents in Sensory Neurons

• Cho JS
• Kim TH
• Shin YK
• Lee CS
• Park M
• Song JH

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.

Keyword

Analgesia; Dorsal root ganglia; Patch-clamp; Sodium channel; Tetrodotoxin; Valdecoxib

MeSH Terms

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
Cyclooxygenase 2
Sodium
Sodium Channels
Tetrodotoxin