Role of Neuroinflammation in the Pathogenesis of Painful Neuropathy in Type 2 Diabetes

Painful diabetic neuropathy (PDN) is an important complication of diabetes. The Zucker diabetic fatty (ZDF) rat is an established model for Type 2 diabetes (T2D). To investigate the potential role of inflammation in the pathogenesis of painful neuropathy in this model, we used a microarray to study cytokine/chemokine expression in the spinal cord dorsal horn and correlated changes in expression of TRPV1 channel which is related to thermal pain. After 6 weeks of hyperglycemia, significant changes were observed in thermal latency and in mechanical pain threshold in ZDF animals compared to their lean controls. Cytokine array revealed elevation in a number of inflammatory mediators that are associated with the emergence of pain-related behaviors. ZDF animals with PDN also exhibited increase in transient receptor potential cation channel subfamily V member 1 (TRPV1) in the DRG and the spinal cord. The increase in inflammatory markers in the spinal cord dorsal horn of Type 2 diabetic animals coincident with the onset of pain in PDN suggests that inflammation in the spinal cord may be important in the development of pain in this model. Abbreviations