A role for proprioceptors in sngception

Science Advances, vol. 11, pp. eabc5219

Abstract

Proprioceptors are primary mechanosensory neurons to monitor the status of muscle contraction and/or body position ( 1 ). Although proprioceptors are known as non-nociceptive mechanoreceptors, they also express the pro-nociceptive acid-sensing ion channel 3 (ASIC3) ( 2 – 5 ). To probe the role for proprioceptors in sensing acidosis (or sngception) ( 6 ), we found that genetic deletion of Asic3 in proprioceptors but not in nociceptors abolished acid-induced chronic hyperalgesia in mice. Chemo-optogenetically activating proprioceptors resulted in hyperalgesic priming that favored chronic pain induced by acidosis. In humans, intramuscular acidification induced acid perception but not pain. Conversely, in a spinal cord–injured patient who lost pain sensation in the right leg, proprioception and sngception were remaining somatosensory functions, associated with the spinal dorsal column. Together, evidence from both mouse and human studies suggests a role for proprioceptors in sngception.

Authors 10

1. Cheng‐Han Lee corresponding

   Institute of Biomedical Sciences, Academia Sinica · Academia Sinica

   Affiliation as printed

   Institute of Biomedical Sciences, Academia Sinica, Taipei 115, Taiwan

2. Jiann-Her Lin corresponding

   Taipei Medical University Hospital · Taipei Medical University

   Affiliation as printed

   Department of Neurosurgery, Taipei Medical University Hospital, Taipei, Taiwan

   Division of Neurosurgery, Department of Surgery, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan

   Taipei Neuroscience Institute, Taipei Medical University, Taipei, Taiwan

3. Shing-Hong Lin corresponding

   Institute of Biomedical Sciences, Academia Sinica · Academia Sinica

   Affiliation as printed

   Institute of Biomedical Sciences, Academia Sinica, Taipei 115, Taiwan

4. Chu-Ting Chang

   Institute of Biomedical Sciences, Academia Sinica · Academia Sinica

   Affiliation as printed

   Institute of Biomedical Sciences, Academia Sinica, Taipei 115, Taiwan

5. Yu‐Wei Wu

   Institute of Molecular Biology, Academia Sinica · Academia Sinica

   Affiliation as printed

   Institute of Molecular Biology, Academia Sinica, Taipei, Taiwan

   Neuroscence Program of Academia Sinica, Academia Sinica, Taipei, Taiwan

6. Guy S. Bewick

   University of Aberdeen

   Affiliation as printed

   Institute of Medical Sciences, University of Aberdeen, Aberdeen AB25 2ZD, UK

7. Robert W. Banks

   Durham University

   Affiliation as printed

   Department of Biosciences, University of Durham, Durham DH1 3LE, UK

8. Stefan Gründer Aachen Institute of Physiology

   RWTH Aachen University

   Affiliation as printed

   Institute of Physiology, Rheinisch-Westfaelische Technische Hochschule (RWTH) Aachen University, 52074 Aachen, Germany

9. Ute Hochgeschwender

   Central Michigan University

   Affiliation as printed

   College of Medicine, Central Michigan University, Mt. Pleasant, MI, USA

10. Chih‐Cheng Chen corresponding

    Institute of Biomedical Sciences, Academia Sinica · Taiwan Mouse Clinic · Academia Sinica

    Affiliation as printed

    Institute of Biomedical Sciences, Academia Sinica, Taipei 115, Taiwan

    Neuroscence Program of Academia Sinica, Academia Sinica, Taipei, Taiwan

    Taiwan Mouse Clinic – National Comprehensive Mouse Phenotyping and Drug Testing Center, Academia Sinica, Taipei 115, Taiwan