Anterior insular cortex mediates hyperalgesia induced by chronic pancreatitis in rats
Anterior insular cortex mediates hyperalgesia induced by chronic pancreatitis in rats
复制标题
DOI：
10.1186/s13041-019-0497-5
复制
发表时间：
2019-09-04
期刊：
影响因子：
3.6
通讯作者：
Li, Yun-Qing
中科院分区：
文献类型：
--
作者：
Bai, Yang;Ma, Li-Tian;Li, Yun-Qing
中枢敏化在慢性胰腺炎（CP）引起的慢性疼痛的维持中起着关键作用，但疼痛性 CP 的皮质调节仍然难以捉摸。本研究旨在探讨前岛叶皮质 (aIC) 在 CP 大鼠模型痛觉过敏发病机制中的作用。 CP是通过导管内施用三硝基苯磺酸(TNBS)诱导的。分别通过冯弗雷丝和旷场测试评估腹部痛觉过敏和焦虑。手术后两周，FOS 免疫组织化学染色和电生理记录表明 aIC 激活。通过免疫印迹分析VGluT1、NMDAR亚基NR2B和AMPAR亚基GluR1的表达。通过药理学方法和化学遗传学在 CP 大鼠中检测 aIC 在痛觉过敏和疼痛相关焦虑中的调节作用。我们的结果表明，TNBS 治疗导致大鼠长期痛觉过敏和焦虑样行为。 CP 大鼠表现出 FOS 表达增加和 aIC 内兴奋性突触传递增强。 CP 大鼠还表现出 VGluT1 表达上调，并且 aIC 内 NR2B 和 GluR1 的膜运输和磷酸化增加。阻断兴奋性突触传递可显着减弱腹部机械痛觉过敏。特别抑制岛锥体细胞的兴奋性可以减少腹部痛觉过敏和与疼痛相关的焦虑。总之，我们的研究结果强调了 aIC 在疼痛性 CP 的痛觉过敏和焦虑中的关键作用，为疼痛性 CP 的皮质调节提供了新的见解，并揭示了 aIC 作为治疗 CP 的神经调节干预的潜在目标。
Central sensitization plays a pivotal role in the maintenance of chronic pain induced by chronic pancreatitis (CP), but cortical modulation of painful CP remains elusive. This study was designed to examine the role of anterior insular cortex (aIC) in the pathogenesis of hyperalgesia in a rat model of CP. CP was induced by intraductal administration of trinitrobenzene sulfonic acid (TNBS). Abdomen hyperalgesia and anxiety were assessed by von Frey filament and open field tests, respectively. Two weeks after surgery, the activation of aIC was indicated by FOS immunohistochemical staining and electrophysiological recordings. Expressions of VGluT1, NMDAR subunit NR2B and AMPAR subunit GluR1 were analyzed by immunoblottings. The regulatory roles of aIC in hyperalgesia and pain-related anxiety were detected via pharmacological approach and chemogenetics in CP rats. Our results showed that TNBS treatment resulted in long-term hyperalgesia and anxiety-like behavior in rats. CP rats exhibited increased FOS expression and potentiated excitatory synaptic transmission within aIC. CP rats also showed up-regulated expression of VGluT1, and increased membrane trafficking and phosphorylation of NR2B and GluR1 within aIC. Blocking excitatory synaptic transmission significantly attenuated abdomen mechanical hyperalgesia. Specifically inhibiting the excitability of insular pyramidal cells reduced both abdomen hyperalgesia and pain-related anxiety. In conclusion, our findings emphasize a key role for aIC in hyperalgesia and anxiety of painful CP, providing a novel insight into cortical modulation of painful CP and shedding light on aIC as a potential target for neuromodulation interventions in the treatment of CP.