Department of Anesthesiology, Pain and Perioperative Medicine, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
Department of Radiation Oncology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
J Alzheimers Dis. 2020;74(3):875-881. doi: 10.3233/JAD-200027.
Persistent neuropathic pain (NP) causes future development of neurodegenerative diseases, e.g., Alzheimer' disease, and thus needs to be optimally treated. Surgically-induced neuropathic pain (SNPP) is a persistent pain that occurs in nearly half of the individuals after common operations. Here, we showed that specific activation of 5-hydroxytryptamine (5-HT) type 2A receptors by systemic administration of TCB-2 [(4-bromo-3,6-dimethoxybenzocyclobuten-1-yl) methylamine hydrobromide] improved the function of potassium chloride cotransporter 2 (KCC2), resulting in reduction in neuropathic pain after chronic constriction injury (CCI), a rat model that mimics SNPP. Moreover, TCB-2 administration attenuated both mechanical and thermal hyperalgesia, likely through augmentation of dorsal horn KCC2 levels, since this effect was abolished by intrathecal provision of dihydroindenyl oxy alkanoic acid (DIOA), which blocked the effects of KCC2. Furthermore, TCB-2-mediated re-activation of KCC2 likely reduces future development of neurodegeneration in rats. Together, our data support further studies on the possibility of using this strategy to reduce postoperative pain and future neurodegenerative disorders in clinic.
持续性神经病理性疼痛（NP）会导致未来发生神经退行性疾病，例如阿尔茨海默病，因此需要进行最佳治疗。手术诱导的神经病理性疼痛（SNPP）是一种常见手术后近一半个体发生的持续性疼痛。在这里，我们表明全身给予 TCB-2[（4-溴-3,6-二甲氧基苯并环丁烯-1-基）甲胺氢溴酸盐]可特异性激活 5-羟色胺（5-HT）2A 受体，从而改善慢性缩窄性损伤（CCI）后钾氯离子共转运体 2（KCC2）的功能，CCI 是一种模拟 SNPP 的大鼠模型。此外，TCB-2 的给药减轻了机械性和热痛觉过敏，可能是通过增加背角 KCC2 水平，因为这种作用被鞘内给予二氢茚基氧烷酸（DIOA）所阻断，DIOA 阻断了 KCC2 的作用。此外，TCB-2 介导的 KCC2 重新激活可能会减少大鼠未来发生神经退行性变的可能性。总之，我们的数据支持进一步研究使用这种策略来减少术后疼痛和未来临床神经退行性疾病的可能性。
