Inhibition of phosphorylated calcium/calmodulin-dependent protein kinase IIα relieves streptozotocin-induced diabetic neuropathic pain through regulation of P2X3 receptor in dorsal root ganglia

[摘要] Diabetic neuropathic pain (DNP) is frequent among patients with diabetes. We previously showed that P2X3 upregulationin dorsal root ganglia (DRG) plays a role in streptozotocin (STZ)-induced DNP but the underlying mechanism is unclear.Here, a rat model of DNP was established by a single injection of STZ (65 mg/kg). Fasting blood glucose was signifcantlyelevated from the 1st to 3rd week. Paw withdrawal thresholds (PWTs) and paw withdrawal latencies (PWLs) in diabetic ratssignifcantly reduced from the 2nd to 3rd week. Western blot analysis revealed that elevated p-CaMKIIα levels in the DRGof DNP rats were accompanied by pain-associated behaviors while CaMKIIα levels were unchanged. Immunofuorescencerevealed signifcant increase in the proportion of p-CaMKIIα immune positive DRG neurons (stained with NeuN) in the 2ndand 3rd week and p-CaMKIIα was co-expressed with P2X3 in DNP rats. KN93, a CaMKII antagonist, signifcantly reducemechanical hyperalgesia and thermal hyperalgesia and these efects varied dose-dependently, and suppressed p-CaMKIIα andP2X3 upregulation in the DRGs of DNP rats. These results revealed that the p-CaMKIIα upregulation in DRG is involvedin DNP, which possibly mediated P2X3 upregulation, indicating CaMKIIα may be an efective pharmacological target forDNP management.

[学科分类] 分子生物学，细胞生物学和基因

[关键词] Diabetic neuropathic pain;p-CaMKIIα;Streptozotocin;DRG;KN93;P2X3 receptor