Celecoxib inhibits Na+ currents in rat dorsal root ganglion neurons.

Celecoxib is a selective cyclooxygenase-2 (COX-2) inhibitor used in the treatment of osteoarthritis and rheumatoid arthritis with fewer gastrointestinal toxicities compared to traditional non-steroidal anti-inflammatory drugs. Voltage-gated Na(+) channels in primary sensory neurons play an important role in the pathogenesis of various pain conditions. We examined the effects of celecoxib on tetrodotoxin-sensitive (TTX-S) and tetrodotoxin-resistant (TTX-R) Na(+) currents in acutely dissociated rat dorsal root ganglion neurons. Celecoxib suppressed both currents in dose- and frequency-dependent manner. The apparent dissociation constants (K(d)) for TTX-S and TTX-R Na(+) currents measured at 0 mV from a holding potential of -80 mV were estimated to be 5.6 and 19.5 microM, respectively. Celecoxib slightly slowed inactivation kinetics of TTX-S Na(+) current, but made it much faster in TTX-R Na(+) current. Celecoxib shifted the activation voltage of TTX-S Na(+) current to a depolarizing direction, but not that of TTX-R Na(+) current. Celecoxib caused a hyperpolarizing shift of the steady-state inactivation curve in both Na(+) currents to a great extent. In addition celecoxib reduced the maximal availability of both Na(+) channels. Thus celecoxib appears to bind to both inactivated and resting Na(+) channels. Celecoxib slowed the recovery of both Na(+) channels from inactivation. All these effects combined would suppress the excitability of sensory neurons. Thus, beside COX-2 inhibition, the Na(+) channel inhibition is considered to contribute to celecoxib analgesia.