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.

目的：确定酸敏感离子通道1（ASIC1）-氯化钠-钾-钾共转运蛋白1（NKCC1）信号传导通路是否参与成年母婴剥夺（NMD）的成年大鼠的慢性内脏痛。

方法：通过结肠直肠扩张（CRD）检测到慢性内脏痛。进行了蛋白质印迹和免疫荧光检测ASIC1和NKCC1的表达和位置。进行全细胞膜片钳记录以记录脊髓突触传递。

结果：NMD大鼠的脊髓背角兴奋性突触传递增强，抑制性突触传递减弱。在NMD大鼠中，脊髓背角中ASIC1和NKCC1蛋白的表达明显上调。阿米洛利的温育降低了mEPSC的幅度。布美他尼（BMT）的孵育增加了mIPSC的幅度。鞘内注射ASIC1或NKCC1抑制剂可逆转NMD大鼠的CRD阈值。同样，阿米洛利治疗显着逆转了NMD大鼠脊髓背角中NKCC1的表达。

结论：我们的数据表明ASIC1-NKCC1信号通路与NMD大鼠的慢性内脏痛有关。