Alloxan as a better option than streptozotocin for studies involving painful diabetic neuropathy.

Previous data indicate that the diabetogenic substance streptozotocin might act in nociceptive neurons changing the sensory signal, regardless of hyperglycemia. In the present article the effects of streptozotocin were compared with another diabetogenic drug, alloxan, for diabetes induction in rats. A possible direct effect of these drugs was tested by means of in vivo experiments and in vitro assays using cultured primary nociceptive neurons. Streptozotocin (17.5 and 35 mg/kg), alloxan (15 and 30 mg/kg) or vehicle were injected in adult male rats and the animal groups were separated according to glycemic levels. Body mass, glycemia and paw mechanical sensitivity were evaluated for 5 weeks. Streptozotocin caused an increase in mechanical sensitivity in both hyperglycemic and normoglycemic rats, while alloxan induced mechanical sensitization only in hyperglycemic animals. Injection of both substances induced local inflammation at rat paws; however, only streptozotocin caused significant mechanical sensitization when injected near to sensory neurons at the dorsal root ganglia. Also, streptozotocin treatment induced a reduction in intracellular calcium levels and inhibited capsaicin induced calcium transients and membrane depolarization. Alloxan did not affect calcium levels or membrane potential in primary nociceptive neurons. These findings suggest that alloxan might be a better option for animal studies regarding painful diabetic neuropathy as streptozotocin directly affects nociceptive neurons, probably by modulating TRPV1 channel activation.

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.