Terahertz Wave Alleviates Comorbidity Anxiety in Pain by Reducing the Binding Capacity of Nanostructured Glutamate Molecules to GluA2
Zihua Song,
Yuankun Sun,
Pan Liu,
Hao Ruan,
Yuanyuan He,
Junkai Yin,
Chun Xiao,
Jing Ma,
Yun Yu,
Shaomeng Wang,
Yubin Gong,
Z. W. Lin,
Zhi Zhang,
Chao Chang,
Maojun Yang
Affiliations
Zihua Song
Innovation Laboratory of Terahertz Biophysics,
National Innovation Institute of Defense Technology, Beijing 100071, China.
Yuankun Sun
School of Electronic Science and Engineering,
University of Electronic Science and Technology of China, Chengdu 611731, China.
Pan Liu
Innovation Laboratory of Terahertz Biophysics,
National Innovation Institute of Defense Technology, Beijing 100071, China.
Hao Ruan
Innovation Laboratory of Terahertz Biophysics,
National Innovation Institute of Defense Technology, Beijing 100071, China.
Yuanyuan He
School of Safety Engineering,
North China Institute of Science and Technology, Hebei 065201, China.
Junkai Yin
Innovation Laboratory of Terahertz Biophysics,
National Innovation Institute of Defense Technology, Beijing 100071, China.
Chun Xiao
School of Life Sciences,
Tsinghua University, Beijing 100081, China.
Jing Ma
Innovation Laboratory of Terahertz Biophysics,
National Innovation Institute of Defense Technology, Beijing 100071, China.
Yun Yu
Innovation Laboratory of Terahertz Biophysics,
National Innovation Institute of Defense Technology, Beijing 100071, China.
Shaomeng Wang
School of Electronic Science and Engineering,
University of Electronic Science and Technology of China, Chengdu 611731, China.
Yubin Gong
School of Electronic Science and Engineering,
University of Electronic Science and Technology of China, Chengdu 611731, China.
Z. W. Lin
Innovation Laboratory of Terahertz Biophysics,
National Innovation Institute of Defense Technology, Beijing 100071, China.
Zhi Zhang
Division of Life Sciences and Medicine, Department of Anesthesiology, the First Affiliated Hospital of USTC, Hefei National Laboratory for Physical Sciences at the Microscale,
University of Science and Technology of China, Hefei 230026, China.
Chao Chang
Innovation Laboratory of Terahertz Biophysics,
National Innovation Institute of Defense Technology, Beijing 100071, China.
Maojun Yang
School of Life Sciences,
Tsinghua University, Beijing 100081, China.
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, 1012 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 (ACCGlu). Using whole-cell recording in ACC slices, we demonstrated that THS (34 THz) effectively inhibited the excitability of ACCGlu. 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 ACCGlu hyperactivity and, as a result, alleviated pain and anxiety-like behaviors. Consistently, inhibition of ACCGlu 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.
