Inhibition of phosphorylated calcium/calmodulin-dependent protein kinase IIα relieves streptozotocin-induced diabetic neuropathic pain through regulation of P2X3 receptor in dorsal root ganglia.
Inhibition of phosphorylated calcium/calmodulin-dependent protein kinase IIα relieves streptozotocin-induced diabetic neuropathic pain through regulation of P2X3 receptor in dorsal root ganglia.
复制标题
磷酸化钙/钙调蛋白依赖性蛋白激酶 IIα 的抑制通过调节背根神经节中的 P2X3 受体缓解链脲佐菌素诱导的糖尿病神经性疼痛。
DOI：
10.1007/s11302-021-09829-z
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发表时间：
2023-03
影响因子：
3.5
通讯作者：
Jiang, Yong-liang
中科院分区：
文献类型：
--
作者：
He, Xiao-fen;Kang, Yu-rong;Fei, Xue-yu;Chen, Lu-hang;Li, Xiang;Ma, Yi-qi;Hu, Qun-qi;Qu, Si-ying;Wang, Han-zhi;Shao, Xiao-mei;Liu, Bo-yi;Yi-Liang;Du, Jun-ying;Fang, Jian-qiao;Jiang, Yong-liang
糖尿病性神经性疼痛（DNP）是糖尿病患者常见的疼痛。我们以前发现背根神经节（DRG）中P2 X3上调在链脲佐菌素（STZ）诱导的DNP中起作用，但其潜在机制尚不清楚。在此，通过单次注射STZ（65 mg/kg）建立DNP大鼠模型。第1 ~ 3周空腹血糖明显升高。糖尿病大鼠的缩爪阈值和缩爪潜伏期从第2周到第3周显著降低。Western blot分析显示DNP大鼠DRG中p-CaMK Ⅱ α水平升高伴随疼痛相关行为，而CaMK Ⅱ α水平不变。免疫荧光显示，DNP大鼠2周和3周时p-CaMK Ⅱ α免疫阳性DRG神经元比例显著增加（NeuN染色），p-CaMK Ⅱ α与P2 X3共表达。CaMKII拮抗剂KN 93可显著降低DNP大鼠的机械痛敏和热痛敏，并呈剂量依赖性，抑制DNP大鼠背根节中p-CaMKIIα和P2 X3的上调。这些结果表明，DRG中p-CaMK Ⅱ α的上调参与了DNP，DNP可能介导P2 X3的上调，表明CaMK Ⅱ α可能是DNP管理的有效药理学靶点。
Diabetic neuropathic pain (DNP) is frequent among patients with diabetes. We previously showed that P2X3 upregulation in 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 significantly elevated from the 1st to 3rd week. Paw withdrawal thresholds (PWTs) and paw withdrawal latencies (PWLs) in diabetic rats significantly reduced from the 2nd to 3rd week. Western blot analysis revealed that elevated p-CaMKIIα levels in the DRG of DNP rats were accompanied by pain-associated behaviors while CaMKIIα levels were unchanged. Immunofluorescence revealed significant increase in the proportion of p-CaMKIIα immune positive DRG neurons (stained with NeuN) in the 2nd and 3rd week and p-CaMKIIα was co-expressed with P2X3 in DNP rats. KN93, a CaMKII antagonist, significantly reduce mechanical hyperalgesia and thermal hyperalgesia and these effects varied dose-dependently, and suppressed p-CaMKIIα and P2X3 upregulation in the DRGs of DNP rats. These results revealed that the p-CaMKIIα upregulation in DRG is involved in DNP, which possibly mediated P2X3 upregulation, indicating CaMKIIα may be an effective pharmacological target for DNP management.
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影响因子：
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作者：
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