2. Academic Validation
  3. Cross-modal cortical circuit for sound sensitivity in neuropathic pain

Cross-modal cortical circuit for sound sensitivity in neuropathic pain

  • Curr Biol. 2025 Feb 24;35(4):831-842.e5. doi: 10.1016/j.cub.2024.12.044.
Yunfeng Mao 1,  Mingjun Zhang 1,  Xiaoqi Peng 2,  Yi Liu 3,  Yehao Liu 4,  Qianhui Xia 4,  Bin Luo 5,  Lin Chen 5,  Zhi Zhang 6,  Yuanyin Wang 7,  Haitao Wang 8
Affiliations

Affiliations

  • 1 Department of Anesthesiology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230026, China.
  • 2 College & Hospital of Stomatology, Anhui Medical University, Key Laboratory of Oral Diseases Research of Anhui Province, Hefei 230022, China; School of Basic Medical Sciences, Anhui Medical University, Hefei 230022, China.
  • 3 China High Magnetic Field Laboratory, CAS Key Laboratory of High Magnetic Field and Ion Beam Physical Biology, HFIPS, Hefei 230031, China.
  • 4 School of Basic Medical Sciences, Anhui Medical University, Hefei 230022, China.
  • 5 Auditory Research Laboratory, Department of Neurobiology and Biophysics, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230026, China.
  • 6 Department of Anesthesiology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230026, China; School of Basic Medical Sciences, Anhui Medical University, Hefei 230022, China; Center for Advance Interdisciplinary Science and Biomedicine of IHM, Hefei 230026, China. Electronic address: zhizhang@ustc.edu.cn.
  • 7 College & Hospital of Stomatology, Anhui Medical University, Key Laboratory of Oral Diseases Research of Anhui Province, Hefei 230022, China. Electronic address: wyy1970548@sohu.com.
  • 8 College & Hospital of Stomatology, Anhui Medical University, Key Laboratory of Oral Diseases Research of Anhui Province, Hefei 230022, China. Electronic address: htwang79@ustc.edu.cn.
PMID: 39889698 DOI: 10.1016/j.cub.2024.12.044
Abstract

Hyperacusis, exaggerated sensitivity to sound, frequently accompanies chronic pain in humans, suggesting interactions between different sensory systems in the brain. However, the neural mechanisms underlying this comorbidity remain largely unexplored. In this study, behavioral tests measuring sound-evoked pupil dilation and reaction times to lick water following auditory stimuli showed hyperacusis-like behaviors in neuropathic pain model mice. Through viral tracing, fiber photometry, and multi-electrode recordings, we identified glutamatergic projections from primary somatosensory cortex (S1HLGlu) to the auditory cortex (ACx) that participate in amplifying sound-evoked neuronal activity following spared nerve injury in the hindlimb. Chemo- or optogenetic manipulation and electrophysiology recordings confirmed that the S1HLGlu → ACx pathway is essential for this heightened response to sound. Specifically, activating this pathway intensified glutamatergic neuronal activity in the ACx and induced hyperacusis-like behaviors, while chemogenetic suppression reversed these effects in neuropathic pain model mice. These findings illustrate the mechanism by which central gain increases in the ACx of neuropathic pain mice, improving our understanding of cross-modal sensory system interactions and suggesting circuit pathway targets for developing interventions to treat pain-associated hyperacusis in clinic.

Keywords

chronic pain; hyperacusis; neural circuit; optogenetics.

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