Mitochondrial Dysfunction in Diabetic Neuropathy May Be Involved in the Development of Neuropathic Pain via a Reduction in Neurosteroid Synthesis

The study suggested that mitochondrial dysfunction in diabetic neuropathy might contribute to neuropathic pain by reducing neurosteroid synthesis. Using whole-cell patch-clamp techniques on neural tissue slices from type-II diabetic (ob/ob) and wild type (WT) mice, it was found that diazepam had an exaggerated effect on GABAergic inhibitory tone in ob/ob mice, even in the presence of the GABAAR antagonist flumazenil. This was likely due to upregulation of neurosteroidogenic enzymes in response to reduced pregnenolone synthesis by the mitochondria. Enhancing neurosteroidogenesis via TSPO activation could potentially restore GABAergic inhibitory tone and offer therapeutic benefits for diabetic neuropathic pain.