Transient receptor melastatin 2 (TRPM2) is a nonselective Ca2+ -permeable cation channel highly expressed in brain and other tissues. Studies showed that TRPM2 contributed to the induction of inflammatory cytokine and chemokine of immune cells, resulted in neuropathic pain. However, how TRPM2 regulates neuropathic pain is not clear. The sciatic nerve chronic constriction injury (CCI) rat model was used to induce chronic neuropathic pain. The RNA and protein level of TRPM2 was detected with real-time PCR and western blot. SiRNA targeting TRPM2 was used to knockdown the expression of TRPM2. Reactive oxygen species (ROS) levels were determined using H2DCFDA assay and NO production was analyzed by measuring the accumulated level of its stable metabolite (nitrite). We found that CCI significantly increased TRPM2 expression in dorsal root ganglion and spinal cord. Knockdown TRPM2 in early phase after CCI alleviated injury-induced neuropathic pain. Mechanistically, we demonstrated that TRPM2 knockdown drastically inhibited the iNOS expression and NO generation, with decreased ROS generation in CCI rat. TRPM2 participates in the transformation of acute pain to chronic pain during injury-induced neuropathic pain, which might serve as a potential therapeutic target for neuropathic pain.

中文翻译：

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TRPM2参与了由损伤引起的神经性疼痛中急性疼痛向慢性疼痛的转化。

瞬时受体褪黑素2（TRPM2）是在脑和其他组织中高度表达的非选择性Ca2 +渗透性阳离子通道。研究表明，TRPM2有助于诱导免疫细胞的炎性细胞因子和趋化因子，导致神经性疼痛。但是，TRPM2如何调节神经性疼痛尚不清楚。坐骨神经慢性收缩损伤（CCI）大鼠模型用于诱发慢性神经性疼痛。实时荧光定量PCR和Western blot检测TRPM2的RNA和蛋白水平。靶向TRPM2的SiRNA用于敲低TRPM2的表达。使用H2DCFDA测定法确定活性氧（ROS）的水平，并通过测量其稳定代谢物（亚硝酸盐）的累积水平来分析NO的产生。我们发现CCI显着增加了背根神经节和脊髓中TRPM2的表达。CCI后早期敲低TRPM2可减轻损伤引起的神经性疼痛。从机理上讲，我们证明了TRPM2敲低能显着抑制iCI的表达和NO的生成，并降低CCI大鼠的ROS生成。TRPM2参与了由损伤引起的神经性疼痛中急性疼痛向慢性疼痛的转化，这可能是神经性疼痛的潜在治疗靶点。