Shi Pei, Zhang Ming-Jun, Liu An, Yang Chen-Ling, Yue Jia-Yin, Hu Rui, Mao Yu, Zhang Zhi, Wang Wei, Jin Yan, Liang Li-Shuang
Department of Anesthesiology, Linyi People's Hospital, Shandong University, Jinan, China.
Stroke Center and Department of Neurology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China.
Front Mol Neurosci. 2023 Jan 12;15:1006125. doi: 10.3389/fnmol.2022.1006125. eCollection 2022.
Pain is commonly comorbid with anxiety; however, the neural and molecular mechanisms underlying the comorbid anxiety symptoms in pain (CASP) have not been fully elucidated. In this study, we explored the role of acid-sensing ion channel 1a (ASIC1a), located in GABAergic neurons from the central nucleus of the amygdala (GABA), in the regulation of CASP in an acute pain mouse model. We found that the mice displayed significant mechanical pain sensitization and anxiety-like behaviors one day post injection of complete Freud's adjuvant (CFA1D). Electrophysiological recordings from acute brain slices showed that the activity of GABA neurons increased in the CFA1D mice compared with that in the saline mice. In addition, chemogenetic inhibition of GABA neurons relieved mechanical pain sensitization and anxiety-like behaviors in the CFA1D mice. Interestingly, through pharmacological inhibition and genetic knockdown of ASIC1a in the central nucleus amygdala, we found that downregulation of ASIC1a relieved the hypersensitization of mechanical stimuli and alleviated anxiety-related behaviors, accompanied with reversing the hyperactivity of GABA neurons in the CFA 1D mice. In conclusion, our results provide novel insights that ASIC1a in GABA neurons regulates anxiety-like behaviors in a mouse model of acute pain.
疼痛通常与焦虑并存；然而，疼痛中共病焦虑症状（CASP）背后的神经和分子机制尚未完全阐明。在本研究中，我们探讨了位于杏仁核中央核（GABA）的GABA能神经元中的酸敏感离子通道1a（ASIC1a）在急性疼痛小鼠模型中对CASP的调节作用。我们发现，在注射完全弗氏佐剂（CFA1D）一天后，小鼠表现出明显的机械性疼痛敏化和焦虑样行为。急性脑片的电生理记录显示，与生理盐水处理的小鼠相比，CFA1D小鼠中GABA神经元的活性增加。此外，对GABA神经元进行化学遗传学抑制可缓解CFA1D小鼠的机械性疼痛敏化和焦虑样行为。有趣的是，通过对杏仁核中央核中的ASIC1a进行药理学抑制和基因敲低，我们发现ASIC1a的下调可缓解机械刺激的超敏反应并减轻焦虑相关行为，同时逆转CFA 1D小鼠中GABA神经元的过度活跃。总之，我们的结果提供了新的见解，即GABA神经元中的ASIC1a在急性疼痛小鼠模型中调节焦虑样行为。
