Hyperglycemia induces mechanical hyperalgesia and depolarization of the resting membrane potential of primary nociceptive neurons: Role of ATP-sensitive potassium channels

Cumulating data suggests that ion channel alterations in nociceptive neurons might be involved in the development of diabetic painful neuropathy. In the present study we investigated the involvement of ATP-sensitive potassium (K+ATP) channels in the acute effect of high glucose solution in vitro and in vivo. High glucose concentrations depolarized cultured nociceptive neurons and depolarization was blocked by the K+ATP opener, diazoxide or by insulin. Glucose injection at the rat dorsal root ganglia (L5) resulted in acute mechanical hyperalgesia that was blocked by diazoxide. Mannitol injection indicates that osmolarity changes are not responsible for glucose effect. Therefore, this study suggests that K+ATP channels expressed in peripheral sensory neurons might be involved in the development of diabetic painful neuropathy. Since sulfonylureas, that act by blocking K+ATP are used for diabetes treatment, it is important to evaluate the possible side effects of such drugs at primary sensory neurons. •High glucose concentrations depolarize cultured DRG neurons.•K+ATP channels are possibly involved in glucose induced depolarization.•High glucose injected at the dorsal root ganglia induces mechanical hyperalgesia.•Diazoxide blocks the increase in glucose-induced mechanical hyperalgesia.