Effects of nordihydroguaiaretic acid on Na+ currents in rat dorsal root ganglion neurons

Nordihydroguaiaretic acid (NDGA) is a lipoxygenase (LO) inhibitor with a strong antioxidant activity. It attenuates nociceptive responses produced by various stimuli, which has been ascribed to its LO inhibition. Primary sensory neurons express multiple Na+ channels that are important in processing normal and abnormal nociception. We examined the effects of NDGA on tetrodotoxin-sensitive and tetrodotoxin-resistant Na+ currents in rat dorsal root ganglion neurons. NDGA inhibited both types of Na+ currents concentration dependently and reversibly. Both activation and inactivation time courses were slowed by NDGA, which were not reversible. NDGA produced a hyperpolarizing shift of the steady-state inactivation curves and reduced the maximal availability of both Na+ currents, indicating that it blocks both inactivated and resting Na+ channels. NDGA shifted the conductance-voltage curves of both Na+ currents toward a depolarizing direction and increased the slope factors of the curves. The recovery of Na+ channels from inactivation was retarded by NDGA. All these effects will reduce the excitability of sensory neurons and should be taken into account when it comes to the antinociceptive effects of NDGA.