Chronic excess of glucose (chronic hyperglycemia) impairs neuron function via the polyol pathway, causing ROS and RNS eventually. These activate nuclear transcription factors that increase the expression of ion channel transducers TRP and NaV and impairs their capacity to self-repair. Meanwhile, microglia-released cytokines, ATP, BDNF, and NO stimulate GPCR and tyrosine kinase receptors. This causes a signaling cascade leading to the phosphorylation of TRP and NaV channels, further distorting normal biology.