In vitro hyperglycemia enhances sodium currents in dorsal root ganglion neurons: An effect attenuated by carbamazepine

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.

► In uncontrolled diabetes hyperglycemia is postulated to produce neuropathy.
► Hence, the effect of hyperglycemia on DRG neurons in vitro was examined.
► Hyperglycemia enhanced the density of total and TTX-resistant INa in DRG neurons.
► Carbamazepine blocked the hyperglycemia-induced increase in Na+ channel activities.
► Hyperglycemia-induced Na+ channel activity is associated with ROS to produce neuronal damage.