A role for proprioceptors in sngception

Cheng-Han  Lee; Jiann-Her  Lin; Chu-Ting  Chang; Yu-Wei  Wu; Guy Bewick; Robert W. Banks; Stefan  Grunder; Ute  Hochgeschwender; Chih-Cheng Chen

doi:10.1126/sciadv.abc5219

A role for proprioceptors in sngception

Cheng-Han Lee, Jiann-Her Lin, Chu-Ting Chang, Yu-Wei Wu, Guy Bewick, Robert W. Banks, Stefan Grunder, Ute Hochgeschwender, Chih-Cheng Chen

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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.

Original language	English
Article number	eabc5219
Number of pages	11
Journal	Science Advances
Volume	11
Issue number	5
Early online date	31 Jan 2025
DOIs	https://doi.org/10.1126/sciadv.abc5219
Publication status	Published - 1 Feb 2025

Bibliographical note

We thank the Transgenic Core Facility of Academia Sinica in generating the Lmo3 and Asic2a−/− mice, the Light Microscopy Core Facility, and Y.-M. Chang of the Institute of Biomedical Sciences, Academia Sinica for the technical assistance in confocal microscopy and analyzing single-cell transcriptomics of human DRG proprioceptors respectively. Also, we thank R. Pellicciari and M. Marinozzi, University of Perugia, Italy for the gift of PCCG-13

Data Availability Statement

All data needed to evaluate the conclusions in the paper are present in the paper and/or the Supplementary Materials. This study includes no dataset deposited in external repositories. The PCCG-13 can be provided by R. Pellicciari and M. Marinozzi. Requests for PCCG-13 should be submitted to: M. Marinozzi, Department of Pharmaceutical Sciences, Via del Liceo, 1, 06123 Perugia, Italy. This may be subject to a material transfer agreement.

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title = "A role for proprioceptors in sngception",

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.",

author = "Cheng-Han Lee and Jiann-Her Lin and Chu-Ting Chang and Yu-Wei Wu and Guy Bewick and Banks, {Robert W.} and Stefan Grunder and Ute Hochgeschwender and Chih-Cheng Chen",

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AU - Chen, Chih-Cheng

N1 - We thank the Transgenic Core Facility of Academia Sinica in generating the Lmo3 and Asic2a−/− mice, the Light Microscopy Core Facility, and Y.-M. Chang of the Institute of Biomedical Sciences, Academia Sinica for the technical assistance in confocal microscopy and analyzing single-cell transcriptomics of human DRG proprioceptors respectively. Also, we thank R. Pellicciari and M. Marinozzi, University of Perugia, Italy for the gift of PCCG-13

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N2 - 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.

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A role for proprioceptors in sngception

Abstract

Bibliographical note

Data Availability Statement

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