In vitro hyperglycemia enhances sodium currents in dorsal root ganglion neurons: an effect attenuated by...

Neuropathy is often seen in uncontrolled diabetes and the mechanisms involved for neuropathic pain are poorly understood. Hyperglycemia is a consequence of chronic uncontrolled diabetes and it is postulated to produce neuropathic pain. Therefore, in this study, we have investigated the effects of hyperglycemia on Na(+) channel kinetics in cultured dorsal root ganglion (DRG) neurons from neonatal rats using whole-cell patch-clamp technique. Hyperglycemia-induced increase in density of tetrodotoxin resistant (TTXr) Na(+) currents was increased in time- and concentration-dependent manner. The increase was maximal with 60 mM and 24 h. There was no change Na(+) current density in time-matched control neurons. The conductance curve of TTXr Na(+) current shifted leftward after 24 h exposure to 45 mM glucose. Carbamazepine (CBZ, 100 μM) depressed TTXr Na(+) current in neurons incubated with control (17.26), 45 and 60 mM of glucose. The depression observed with CBZ in the presence of high glucose, i.e., 45 mM (86.5±4.9%) was significantly greater than control (61.6±1.8%). Hyperglycemia also increased reactive oxygen species (ROS) activity and was attenuated by CBZ. These results suggest that short-term exposure of DRG neurons to high glucose concentrations enhance the Na(+) channel activity, and were attenuated by CBZ via ROS-dependent mechanisms.