Peripheral diabetic neuropathy (DN) affects 50% of Diabetes Mellitus (DM) patients and approximately 40-50% progress to painful diabetic neuropathy (pDN). Risk factors for pDN include high alcohol consumption, obesity, and low vitamin D levels, all associated with impaired oligodendrocyte progenitor cell (OPC) differentiation. Additionally, studies indicate that depletion of mature myelinating oligodendrocytes induces nociceptive responses in mice. These findings suggest that DM might disrupt oligodendrocyte dynamics, causing defects in central nervous system (CNS) myelin and the onset of neuropathic pain. To investigate the impact of CNS demyelination on the development of neuropathic pain symptoms in the context of pDN, demyelination is genetically induced in a murine model during a high-fat-high-sugar (HFHS) diet supplementation. Nociceptive responses, including thermal hyperalgesia, cold, and mechanical allodynia, are monitored to identify mice exhibiting pain-like behaviors. Furthermore, a genetic mouse model for fluorescent labeling of OPCs and myelin is employed to explore the effect of HFHS diet supplementation on CNS myelin morphology and oligodendrocyte dynamics. Our results so far indicate that the SHIELD transformation strategy for whole-CNS tissue clearing is suitable for our purposes. This protocol allows for the protection of the physiochemical properties and ensures proper fluorescent preservation of both brain and spinal cord tissue. Therefore, enabling us to image myelin dynamics throughout the CNS. This research seeks to advance our understanding of pDN and contribute valuable insights that may inform the development of novel and targeted treatment approaches.