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Peer-reviewedCC BY 4.0Frontiers in Pharmacology

Acid-sensing ion channels in pain and psychiatric disorders: from basic properties to comorbidity mechanisms

  • Congcong Li1,2
  • Lei Ye1,2
  • Shuna Qin1,2
  • Ying Zeng1,2
  • Yuquan Sun1,2
  • Hang Lv3
  • Chuan’an Zhu4
  • Yiqiu Lin5
  • Chaofan Wan1,2,6
6 affiliations
  1. 1School of Chinese Medicine, Guangdong Pharmaceutical University
  2. 2Guangdong Provincial Engineering and Technology Research Center of Light and Health, Guangdong Pharmaceutical University
  3. 3Sleep Research Institute of Traditional Chinese Medicine, The Affiliated Traditional Chinese Medicine Hospital, Guangzhou Medical University
  4. 4Xiamen Xianyue Hospital, Xianyue Hospital Affiliated with Xiamen Medical College, Fujian Psychiatric Center, Fujian Clinical Research Center for Mental Disorders
  5. 5Department of Rehabilitation Medicine, The Third Affiliated Hospital of Sun Yat-Sen University
  6. 6South China Research Center for Acupuncture and Moxibustion, Medical College of Acu-Moxi and Rehabilitation, Guangzhou University of Chinese Medicine
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Abstract

Acid-sensing ion channels (ASICs) are proton-gated cation channels that mediate Na ⁺ and Ca ²⁺ influx upon activation by extracellular acidification. Beyond protons, endogenous ligands, toxins, and small molecules modulate ASIC gating through direct or synergistic mechanisms. ASICs have emerged as key players in pain and psychiatric disorders. Tissue acidosis drives hyperalgesia via sustained ASIC activation, synaptic plasticity disruption, and central sensitization, thereby promoting chronic pain. In limbic circuits, ASIC1a expression in the amygdala, periaqueductal gray, and dorsal raphe nucleus links these channels to anxiety and depression, with ASIC1a antagonists demonstrating robust efficacy in preclinical models. Selective ASIC modulators represent promising therapeutic candidates for pain-psychiatric comorbidities. This review integrates ASIC biophysical properties with their molecular and circuit-level mechanisms in disease, offering a framework to guide future translational efforts targeting ASIC-mediated pathologies.

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Cite

BibTeXRIS
BibTeX
@article{li2026acidsensing,
  title = {{Acid-sensing ion channels in pain and psychiatric disorders: from basic properties to comorbidity mechanisms}},
  author = {Congcong Li and Lei Ye and Shuna Qin and Ying Zeng and Yuquan Sun and Hang Lv and Chuan’an Zhu and Yiqiu Lin and Chaofan Wan},
  journal = {Frontiers in Pharmacology},
  year = {2026},
  month = nov,
  doi = {10.3389/fphar.2026.1967840},
  url = {https://www.frontiersin.org/articles/10.3389/fphar.2026.1967840/full},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Acid-sensing ion channels in pain and psychiatric disorders: from basic properties to comorbidity mechanisms
AU  - Congcong Li
AU  - Lei Ye
AU  - Shuna Qin
AU  - Ying Zeng
AU  - Yuquan Sun
AU  - Hang Lv
AU  - Chuan’an Zhu
AU  - Yiqiu Lin
AU  - Chaofan Wan
PY  - 2026
DA  - 2026/11/03
JO  - Frontiers in Pharmacology
DO  - 10.3389/fphar.2026.1967840
UR  - https://www.frontiersin.org/articles/10.3389/fphar.2026.1967840/full
AB  - Acid-sensing ion channels (ASICs) are proton-gated cation channels that mediate Na ⁺ and Ca ²⁺ influx upon activation by extracellular acidification. Beyond protons, endogenous ligands, toxins, and small molecules modulate ASIC gating through direct or synergistic mechanisms. ASICs have emerged as key players in pain and psychiatric disorders. Tissue acidosis drives hyperalgesia via sustained ASIC activation, synaptic plasticity disruption, and central sensitization, thereby promoting chronic pain. In limbic circuits, ASIC1a expression in the amygdala, periaqueductal gray, and dorsal raphe nucleus links these channels to anxiety and depression, with ASIC1a antagonists demonstrating robust efficacy in preclinical models. Selective ASIC modulators represent promising therapeutic candidates for pain-psychiatric comorbidities. This review integrates ASIC biophysical properties with their molecular and circuit-level mechanisms in disease, offering a framework to guide future translational efforts targeting ASIC-mediated pathologies.
SN  - 1663-9812
ER  -