Song Zihua, Sun Yuankun, Liu Pan, Ruan Hao, He Yuanyuan, Yin Junkai, Xiao Chun, Ma Jing, Yu Yun, Wang Shaomeng, Gong Yubin, Lin Z W, Zhang Zhi, Chang Chao, Yang Maojun
Innovation Laboratory of Terahertz Biophysics, National Innovation Institute of Defense Technology, Beijing 100071, China.
School of Electronic Science and Engineering, University of Electronic Science and Technology of China, Chengdu 611731, China.
Research (Wash D C). 2024 Dec 11;7:0535. doi: 10.34133/research.0535. eCollection 2024.
Comorbid anxiety in chronic pain is clinically common, with a comorbidity rate of over 50%. The main treatments are based on pharmacological, interventional, and implantable approaches, which have limited efficacy and carry a risk of side effects. Here, we report a terahertz (THz, 10 Hz) wave stimulation (THS) technique, which exerts nonthermal, long-term modulatory effects on neuronal activity by reducing the binding between nano-sized glutamate molecules and GluA2, leading to the relief of pain and comorbid anxiety-like behaviors in mice. In mice with co-occurring anxiety and chronic pain induced by complete Freund's adjuvant (CFA) injection, hyperactivity was observed in glutamatergic neurons in the anterior cingulate cortex (ACC). Using whole-cell recording in ACC slices, we demonstrated that THS (34 THz) effectively inhibited the excitability of ACC. Moreover, molecular dynamics simulations showed that THS reduced the number of hydrogen bonds bound between glutamate molecules and GluA2. Furthermore, THS target to the ACC in CFA-treatment mice suppressed ACC hyperactivity and, as a result, alleviated pain and anxiety-like behaviors. Consistently, inhibition of ACC hyperactivity by chemogenetics mimics THS-induced antinociceptive and antianxiety behavior. Together, our study provides evidence for THS as an intervention technique for modulating neuronal activity and a viable clinical treatment strategy for pain and comorbid anxiety.
慢性疼痛中的共病性焦虑在临床上很常见，共病率超过50%。主要治疗方法基于药物、介入和植入方法，这些方法疗效有限且有副作用风险。在此，我们报告一种太赫兹（THz，10赫兹）波刺激（THS）技术，它通过减少纳米级谷氨酸分子与GluA2之间的结合，对神经元活动产生非热的长期调节作用，从而减轻小鼠的疼痛和共病性焦虑样行为。在通过注射完全弗氏佐剂（CFA）诱导出共病性焦虑和慢性疼痛的小鼠中，观察到前扣带回皮质（ACC）中的谷氨酸能神经元活动亢进。利用ACC脑片的全细胞记录，我们证明THS（34太赫兹）能有效抑制ACC的兴奋性。此外，分子动力学模拟表明THS减少了谷氨酸分子与GluA2之间结合的氢键数量。此外，对CFA处理小鼠的ACC进行THS靶向抑制了ACC的活动亢进，结果减轻了疼痛和焦虑样行为。同样，通过化学遗传学抑制ACC活动亢进模拟了THS诱导的抗伤害感受和抗焦虑行为。总之，我们的研究为THS作为调节神经元活动的干预技术以及疼痛和共病性焦虑的可行临床治疗策略提供了证据。
