Painful diabetic neuropathy (pDN) is a serious, chronic complication affecting about 10-20% of diabetes mellitus (DM) patients, but the underlying cause remains unknown. Hints from risk factor assessment and literature point towards a role of oligodendrocyte and myelin homeostasis. Along this line, the main aim of the project is to identify adaptations occurring in the oligodendrocyte lineage due to the metabolic imbalances triggered by DM and determine which of these adaptations are crucial for the development of neuropathic pain. The high-fat high-sugar diet-induced type 2 DM mouse model is used in combination with behavioural testing to identify the subpopulation of mice that develop neuropathic pain symptoms. Further, oligodendrocyte transcriptome is analysed by snRNA-seq to compare to that of their diabetic littermates that did not develop pain symptoms. The identified pain-related adaptations are going to be further validated in pDN postmortem patient samples to determine those with the highest translational value. Our behavioural analysis revealed that CNS demyelination triggers mechanical hypersensitivity in female mice. Thermal hypersensitivity was not observed and animals avoided cold in the temperature gradient test. Additionally, mice which developed demyelination exhibited increased glycemic levels compared to control littermates. Overall our results suggest that myelin is important for the processing of noxious mechanical stimuli in female mice. Therefore, disruption of CNS myelin can contribute to the development of pain-like behaviour.