Spared but Not Silent: Ion Channel Plasticity in Uninjured Sensory Neurons in Neuropathic Pain

Speidell, Andrew; Khanna, Rajesh; Gomez, Kimberly

doi:10.3390/ijms27188365

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Spared but Not Silent: Ion Channel Plasticity in Uninjured Sensory Neurons in Neuropathic Pain

by

Andrew Speidell

¹,

Rajesh Khanna

² and

Kimberly Gomez

^1,*

¹

Department of Biomedical Sciences, Texas A&M University, Dallas, TX 75246, USA

²

Department of Pharmacology & Therapeutics, University of Florida, Gainesville, FL 32603, USA

^*

Author to whom correspondence should be addressed.

Int. J. Mol. Sci. 2026, 27(18), 8365; https://doi.org/10.3390/ijms27188365 (registering DOI)

Submission received: 7 August 2026 / Revised: 10 September 2026 / Accepted: 10 September 2026 / Published: 19 September 2026

(This article belongs to the Special Issue Targeting Ion Channels for Novel Therapeutics)

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Abstract

Chronic pain is maintained by persistent, maladaptive molecular processes, many of which converge on ion channels. In sensory neurons, these processes include transcriptional reprogramming, altered trafficking, and remodeling of the channel complexes that set membrane excitability. Accumulating evidence indicates that the major ion channel changes driving chronification of neuropathic pain are not restricted to injured sensory neurons but also arise within the adjacent population of spared neurons. Here we review the ion channel alterations that sustain chronic pain states, the mechanisms by which neurons modulate expression of these channels, and the electrophysiological and functional consequences of these shifts in expression profile. We close by examining existing therapeutics directed at these channels and their regulatory mechanisms, which may offer means of interrupting the maintenance of neuropathic pain.

Keywords: neuropathic pain; spared nerve fibers; uninjured sensory neurons; dorsal root ganglion; voltage-gated ion channels; ligand-gated ion channels; calcium activated chloride channels; TRP channels; Na_V1.8; Suzetrigine; CRMP2

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MDPI and ACS Style

Speidell, A.; Khanna, R.; Gomez, K. Spared but Not Silent: Ion Channel Plasticity in Uninjured Sensory Neurons in Neuropathic Pain. Int. J. Mol. Sci. 2026, 27, 8365. https://doi.org/10.3390/ijms27188365

AMA Style

Speidell A, Khanna R, Gomez K. Spared but Not Silent: Ion Channel Plasticity in Uninjured Sensory Neurons in Neuropathic Pain. International Journal of Molecular Sciences. 2026; 27(18):8365. https://doi.org/10.3390/ijms27188365

Chicago/Turabian Style

Speidell, Andrew, Rajesh Khanna, and Kimberly Gomez. 2026. "Spared but Not Silent: Ion Channel Plasticity in Uninjured Sensory Neurons in Neuropathic Pain" International Journal of Molecular Sciences 27, no. 18: 8365. https://doi.org/10.3390/ijms27188365

APA Style

Speidell, A., Khanna, R., & Gomez, K. (2026). Spared but Not Silent: Ion Channel Plasticity in Uninjured Sensory Neurons in Neuropathic Pain. International Journal of Molecular Sciences, 27(18), 8365. https://doi.org/10.3390/ijms27188365

Note that from the first issue of 2016, this journal uses article numbers instead of page numbers. See further details here.

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Spared but Not Silent: Ion Channel Plasticity in Uninjured Sensory Neurons in Neuropathic Pain

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