Study of the Involvement of the P2Y12 Receptor in Chronic Itching in Type 2 Diabetes Mellitus

Itching is a common clinical symptom in diabetic patients. This research is to carry out experiments on the pathological changes in the P2Y12 receptor in type 2 diabetes mellitus complicated with chronic itching. Changes in body weight, fasting blood glucose (FBG), thermal hyperalgesia, cold hyperalgesia, spontaneous itching, and sciatic nerve conduction velocity were detected. The content of reactive oxygen species (ROS) in the dorsal root ganglion was detected by chemical fluorescence. The expression of the P2Y12 receptor, NLRP3, ASC, interleukin-1β (IL-1β), and IL-18 was detected by Western blotting, real-time quantitative PCR, immunofluorescence double labelling, and enzyme-linked immunosorbent assay. Itching and pain behaviours of the mice in the type 2 diabetes mellitus + itch group were significantly increased, and the expression of P2Y12 and NLRP3 as well as the content of ROS increased, and these changes were significantly reversed by treatment with P2Y12 short hairpin RNA (shRNA) or P2Y12 antagonist ticagrelor. Upregulated P2Y12 receptor expression after the activation of satellite glial cells contributes to the increase in ROS content in vivo, followed by NLRP3 inflammasome activation, increased inflammatory cytokine release, and damage to peripheral nerves, which leads to chronic itching. Treatment with P2Y12 shRNA or ticagrelor can inhibit these pathological changes, thus improving itching behaviour.Graphical abstractDevelopment mechanism of diabetes mellitus complicated with chronic itching. Notes: The upregulation of P2Y12 receptor expression and the activation of SGCs lead to the increase of ROS content in vivo, followed by the activation of NLRP3 inflammasome, the increase of inflammatory cytokine release, the abnormal excitation of DRG neurons, and the damage of peripheral nerves, resulting in chronic itching. P2Y12 receptor–related inflammatory injury involves chronic itching in type 2 diabetes mellitus. Treatment with P2Y12 receptor shRNA or P2Y12 antagonist ticagrelor can inhibit these pathological changes and improve itching behaviour.