持续性神经性疼痛(NP)导致神经退行性疾病的未来发展,例如,阿尔茨海默病,因此需要得到最佳处理。手术诱发的神经性疼痛(SNPP)是一种持续性疼痛,在普通手术后几乎一半的个体中发生。这里,我们表明,通过全身给药TCB-2[(4-溴-3,6-二甲氧基苯并环丁烯-1-基)甲胺氢溴酸]特异性激活5-羟色胺(5-HT)2A型受体可改善氯化钾共转运蛋白2(KCC2)的功能,导致慢性压迫性损伤(CCI)后神经性疼痛的减少,模拟SNPP的大鼠模型。此外,TCB-2给药减弱了机械和热痛觉过敏,可能是通过增加背角KCC2水平,由于鞘内提供二氢茚基氧基链烷酸(DIOA)消除了这种作用,这阻止了KCC2的影响。此外,TCB-2介导的KCC2的再激活可能减少大鼠神经变性的未来发展。一起,我们的数据支持对临床使用该策略减轻术后疼痛和未来神经退行性疾病的可能性的进一步研究.
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.