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PreprintCC BYbioRxiv

Precision cell-state silencing of injured afferents alleviates spontaneous neuropathic pain

  • A. H. Cooper
  • P. Chrysostomidou
  • A. Jurado Santos
  • H. Cui
  • S. Adesida
  • M. Redondo Canales
  • A. Bakina
  • A. M. Barry
  • G. Baskozos
  • D. L. Bennett
  • G. A. Weir1
  1. 1University of Glasgow
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Abstract

Excessive primary afferent activity sustains neuropathic pain, but safe and effective therapeutic inhibition has proved elusive. Realising the promise of gene therapies to meet this challenge requires strategies to identify and selectively target the neuronal populations responsible. Here, we use chemo- and optogenetic approaches to demonstrate that activity in injured afferents drives spontaneous pain but is dispensable for normal sensory function, thereby creating a therapeutic opportunity. Guided by chromatin accessibility profiling, we create an injury-responsive viral vector that confers >95% specificity for injured sensory neurons. Combined with the translationally relevant chemogenetic PSAM4-GlyR, this targeting module effectively silences hyperexcitable human sensory neurons and alleviates spontaneous neuropathic pain in mice. These findings establish precision cell-state targeting of sensory neurons as a promising therapeutic strategy for chronic pain.

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Cite

BibTeXRIS
BibTeX
@misc{cooper2026precision,
  title = {{Precision cell-state silencing of injured afferents alleviates spontaneous neuropathic pain}},
  author = {A. H. Cooper and P. Chrysostomidou and A. Jurado Santos and H. Cui and S. Adesida and M. Redondo Canales and A. Bakina and A. M. Barry and G. Baskozos and D. L. Bennett and G. A. Weir},
  howpublished = {bioRxiv},
  year = {2026},
  month = oct,
  doi = {10.64898/2026.10.08.757642},
  url = {https://www.biorxiv.org/content/10.64898/2026.10.08.757642v1},
  note = {CC BY},
}
RIS
TY  - UNPB
TI  - Precision cell-state silencing of injured afferents alleviates spontaneous neuropathic pain
AU  - A. H. Cooper
AU  - P. Chrysostomidou
AU  - A. Jurado Santos
AU  - H. Cui
AU  - S. Adesida
AU  - M. Redondo Canales
AU  - A. Bakina
AU  - A. M. Barry
AU  - G. Baskozos
AU  - D. L. Bennett
AU  - G. A. Weir
PY  - 2026
DA  - 2026/10/08
PB  - bioRxiv
DO  - 10.64898/2026.10.08.757642
UR  - https://www.biorxiv.org/content/10.64898/2026.10.08.757642v1
AB  - Excessive primary afferent activity sustains neuropathic pain, but safe and effective therapeutic inhibition has proved elusive. Realising the promise of gene therapies to meet this challenge requires strategies to identify and selectively target the neuronal populations responsible. Here, we use chemo- and optogenetic approaches to demonstrate that activity in injured afferents drives spontaneous pain but is dispensable for normal sensory function, thereby creating a therapeutic opportunity. Guided by chromatin accessibility profiling, we create an injury-responsive viral vector that confers >95% specificity for injured sensory neurons. Combined with the translationally relevant chemogenetic PSAM4-GlyR, this targeting module effectively silences hyperexcitable human sensory neurons and alleviates spontaneous neuropathic pain in mice. These findings establish precision cell-state targeting of sensory neurons as a promising therapeutic strategy for chronic pain.
ER  -