TWIK-1 plays distinct roles in spinal and peripheral sensory circuits controlling mechanical sensitivity and neuropathic hypersensitivity

Ion channels are essential for sensing somatic stimuli, and their dysregulation can cause chronic conditions such as neuropathic pain. Although the potassium channel Twik-1 has been linked to sensory processing, its specific roles in the somatosensory system under normal and disease conditions remain unclear. Here, we demonstrate that systemic deletion of Twik-1 selectively reduces innocuous tactile and noxious mechanosensation evoked by both static and dynamic mechanical stimuli and facilitates recovery from mechanical hypersensitivity after peripheral nerve injury. Conditional deletion of Twik-1 in spinal cord neurons, pan-inhibitory neurons, or spinal inhibitory interneurons consistently disrupts innocuous tactile and noxious mechanical sensitivity, while sparing responses to high-intensity mechanical stimulation as well as noxious heat and cold. Notably, these manipulations do not affect nerve injury-induced mechanical hypersensitivity. In contrast, selective deletion of Twik-1 in dorsal root ganglion (DRG) neurons preserves baseline somatosensory and nociceptive functions, including innocuous tactile and noxious mechanical sensitivity, but impairs the persistence of mechanical hypersensitivity after nerve injury. This reduction in hypersensitivity is accompanied by decreased aberrant excitability in injured DRG neurons and distinct transcriptional changes. Together, these results suggest that Twik-1 facilitates innocuous tactile and noxious mechanosensation through spinal inhibitory circuits under baseline conditions, while supporting the maintenance of neuropathic pain via its functions in primary sensory neurons.

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Publication Details

Journal
Signal Transduction and Targeted Therapy
Published
2026-06-25
DOI
https://doi.org/10.1038/s41392-026-02748-8
Primary Topic
Ion channel regulation and function
Type
article
Field-Weighted Citation Impact
0.00

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article

TWIK-1 plays distinct roles in spinal and peripheral sensory circuits controlling mechanical sensitivity and neuropathic hypersensitivity

Byung‐Chang Suh, Jonghoon Jung, Young Hoon Sung, Mi‐Ryoung Song et al.
Signal Transduction and Targeted Therapy
Ion channel regulation and function
article

TWIK-1 plays distinct roles in spinal and peripheral sensory circuits controlling mechanical sensitivity and neuropathic hypersensitivity

Byung‐Chang Suh, Jonghoon Jung, Young Hoon Sung, Mi‐Ryoung Song, Jaekwang Lee, Eunsil Cho, Yong Geon Kim, Junsu Kim, Tery Yun, Yu Shin Kim, Eun Yeong Lim, Hwang Eun-Mi, Seo Young Yang, Pojeong Park, Myungin Bæk, Yan Zhang, Junhee Park, Jae‐Yong Park, Hyeonwi Son, Yunjeong Lee, Jin-Nyeong Woo, Hyosang Lee, Jae Hyuk Jeon, Seojung Kim, John Shannonhouse
article en

Abstract

Ion channels are essential for sensing somatic stimuli, and their dysregulation can cause chronic conditions such as neuropathic pain. Although the potassium channel Twik-1 has been linked to sensory processing, its specific roles in the somatosensory system under normal and disease conditions remain unclear. Here, we demonstrate that systemic deletion of Twik-1 selectively reduces innocuous tactile and noxious mechanosensation evoked by both static and dynamic mechanical stimuli and facilitates recovery from mechanical hypersensitivity after peripheral nerve injury. Conditional deletion of Twik-1 in spinal cord neurons, pan-inhibitory neurons, or spinal inhibitory interneurons consistently disrupts innocuous tactile and noxious mechanical sensitivity, while sparing responses to high-intensity mechanical stimulation as well as noxious heat and cold. Notably, these manipulations do not affect nerve injury-induced mechanical hypersensitivity. In contrast, selective deletion of Twik-1 in dorsal root ganglion (DRG) neurons preserves baseline somatosensory and nociceptive functions, including innocuous tactile and noxious mechanical sensitivity, but impairs the persistence of mechanical hypersensitivity after nerve injury. This reduction in hypersensitivity is accompanied by decreased aberrant excitability in injured DRG neurons and distinct transcriptional changes. Together, these results suggest that Twik-1 facilitates innocuous tactile and noxious mechanosensation through spinal inhibitory circuits under baseline conditions, while supporting the maintenance of neuropathic pain via its functions in primary sensory neurons.

Signal Transduction and Targeted TherapyVol. 11(1)
Ulsan College (KR), Daegu Gyeongbuk Institute of Science and Technology (KR), Korea University (KR), University of Alabama at Birmingham (US), Gwangju Institute of Science and Technology (KR), University of Ulsan (KR), Korea Food Research Institute (KR), Korea Basic Science Institute (KR), Korea Brain Research Institute (KR), Korea University (JP), Korea Institute of Science and Technology (KR)
Foundation for the National Institutes of Health, Johns Hopkins University, National Research Foundation, Seoul National University, Yonsei University, Korea University, National Research Foundation of Korea, Daegu Gyeongbuk Institute of Science and Technology, Samsung Science and Technology Foundation, National Institutes of Health, Samsung, National Institute of Dental and Craniofacial Research
Good health and well-being
Openalex Percentile: Top 11%
Ion channel regulation and function
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