Upregulation of Spinal ASIC1 and NKCC1 Expression Contributes to Chronic Visceral Pain in Rats.

Upregulation of Spinal ASIC1 and NKCC1 Expression Contributes to Chronic Visceral Pain in Rats.
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脊髓 ASIC1 和 NKCC1 表达上调导致大鼠慢性内脏疼痛

DOI:
10.3389/fnmol.2020.611179
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发表时间:
2020
影响因子:
4.8
通讯作者:
Xu GY
Xu GY
中科院分区:
医学2区
文献类型:
--
作者:
Li YC;Tian YQ;Wu YY;Xu YC;Zhang PA;Sha J;Xu GY

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目的:探讨酸敏感离子通道1(ASIC 1)-钠钾氯协同转运蛋白1(NKCC 1)信号通路是否参与了新生儿母亲剥夺(NMD)成年大鼠慢性内脏痛的发生。方法:采用结直肠扩张法(CRD)检测慢性内脏痛。Western blotting和免疫荧光法检测ASIC 1和NKCC 1的表达和定位。全细胞膜片钳记录脊髓突触传递。结果如下:NMD大鼠脊髓背角兴奋性突触传递增强,抑制性突触传递减弱。NMD大鼠脊髓背角ASIC 1和NKCC 1蛋白表达显著上调。阿米洛利的孵育降低了mEPSC的幅度。布美他尼(BMT)的孵育增加了mIPSC的振幅。鞘内注射ASIC 1或NKCC 1抑制剂可逆转NMD大鼠的CRD阈值。此外,阿米洛利治疗显着逆转NMD大鼠脊髓背角NKCC 1的表达。结论:ASIC 1-NKCC 1信号通路参与了NMD大鼠慢性内脏痛的发生。
Aims: To determine whether acid-sensing ion channel 1 (ASIC1)–sodium-potassium-chloride cotransporter 1 (NKCC1) signaling pathway participates in chronic visceral pain of adult rats with neonatal maternal deprivation (NMD). Methods: Chronic visceral pain was detected by colorectal distension (CRD). Western blotting and Immunofluorescence were performed to detect the expression and location of ASIC1 and NKCC1. Whole-cell patch-clamp recordings were performed to record spinal synaptic transmission. Results: The excitatory synaptic transmission was enhanced and the inhibitory synaptic transmission was weakened in the spinal dorsal horn of NMD rats. ASIC1 and NKCC1 protein expression in the spinal dorsal horn was significantly up-regulated in NMD rats. Incubation of Amiloride reduced the amplitude of mEPSCs. Incubation of Bumetanide (BMT) increased the amplitude of mIPSCs. Intrathecal injection of ASIC1 or NKCC1 inhibitors reversed the threshold of CRD in NMD rats. Also, Amiloride treatment significantly reversed the expression of NKCC1 in the spinal dorsal horn of NMD rats. Conclusion: Our data suggest that the ASIC1-NKCC1 signaling pathway is involved in chronic visceral pain in NMD rats.
DOI: 10.1002/ejp.1534
发表时间: 2020-02-05
影响因子: 3.6
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