ArticleThe Journal of clinical investigation2019
Schwann cells expressing nociceptive channel TRPA1 orchestrate ethanol-evoked neuropathic pain in mice.
Article in The Journal of clinical investigation, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 papers.
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Who cites it
62 citing papers in PubMed, 127 citations in OpenAlex.
- Alcohol and Hypertension-A Fresh Look on the Mechanistic Aspects of a Fatal Epidemiologic Relationship.Biomolecules · 2026Review
- Distinct Role of Specialized Cutaneous Schwann Cell Network in Acute and Chronic Pain Sensation.Neuroscience bulletin · 2026Article
- Neuromodulation Techniques Alleviating Neuropathic Pain by Targeting Microglia: A Narrative Review.Pain and therapy · 2026Review
- A delayed endothelial-glial mechanism for CGRP-induced migraine.The journal of headache and pain · 2026Review
- MAPK-dependent release of GDNF from Schwann cells mediates tumor-independent pain in neurofibromatosis 1.Science signaling · 2026Article
- Schwann Cell TRPA1, a Proalgesic Ion Channel, Mediates Neuroinflammation and Fibromyalgia-Associated Behaviours in Mice.Journal of neurochemistry · 2026Review
- The Hypothesis of Myelinodegeneration as an Initial Risk of Neuropathic Pain.Neuroscience bulletin · 2026Review
- Article
- Nociceptive Schwann Cells Enter the Sensory Spotlight.The Journal of investigative dermatology · 2026Article
- Chronic alcohol consumption downregulates TRPA1 ion channel and the main peptidergic messengers of the Edinger-Westphal nucleus.Scientific reports · 2025Article
- Alcohol use disorder-associated pain: clinical and preclinical evidence.Alcohol (Fayetteville, N.Y.) · 2025Review
- A conceptual framework for the intersection of hyperalgesia and hyperkatifeia in alcohol addiction.Alcohol (Fayetteville, N.Y.) · 2025Review
- Not Just Neurons: Pain Is Orchestrated in Partnership with Many Non-neuronal Cells.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2025Review
- Transcriptomic and network analyses of an alcohol-induced peripheral neuropathy model identify putative role for histone demethylasebioRxiv : the preprint server for biology · 2025Article
- Chronic intermittent ethanol produces nociception through endocannabinoid-independent mechanisms in mice.Neuropharmacology · 2025Article
- Exploring the epigenetic modifications of the RONS-TRPA1-CGRP axis in migraine pathophysiology.The journal of headache and pain · 2025Review
- Pain Signaling by GPCRs and RTKs.Trends in pharmacological sciences · 2025Review
- Role of Exercise on Neuropathic Pain in Preclinical Models: Perspectives for Neuroglia.Molecular neurobiology · 2025Review
- Unveiling the Mechanisms of Pain in Endometriosis: Comprehensive Analysis of Inflammatory Sensitization and Therapeutic Potential.International journal of molecular sciences · 2025Review
- Regulatory Action of Calcium and Calcium Channels in Pain Pathways.International journal of biological sciences · 2025Review
2 more citing papers are in PubMed but not listed here.
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Authors and funding
11 authors at 6 institutions in 3 countries.
Funding
Abstract
Excessive alcohol consumption is associated with spontaneous burning pain, hyperalgesia, and allodynia. Although acetaldehyde has been implicated in the painful alcoholic neuropathy, the mechanism by which the ethanol metabolite causes pain symptoms is unknown. Acute ethanol ingestion caused delayed mechanical allodynia in mice. Inhibition of alcohol dehydrogenase (ADH) or deletion of transient receptor potential ankyrin 1 (TRPA1), a sensor for oxidative and carbonyl stress, prevented allodynia. Acetaldehyde generated by ADH in both liver and Schwann cells surrounding nociceptors was required for TRPA1-induced mechanical allodynia. Plp1-Cre Trpa1fl/fl mice with a tamoxifen-inducible specific deletion of TRPA1 in Schwann cells revealed that channel activation by acetaldehyde in these cells initiates a NADPH oxidase-1-dependent (NOX1-dependent) production of hydrogen peroxide (H2O2) and 4-hydroxynonenal (4-HNE), which sustains allodynia by paracrine targeting of nociceptor TRPA1. Chronic ethanol ingestion caused prolonged mechanical allodynia and loss of intraepidermal small nerve fibers in WT mice. While Trpa1-/- or Plp1-Cre Trpa1fl/fl mice did not develop mechanical allodynia, they did not show any protection from the small-fiber neuropathy. Human Schwann cells express ADH/TRPA1/NOX1 and recapitulate the proalgesic functions of mouse Schwann cells. TRPA1 antagonists might attenuate some symptoms of alcohol-related pain.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.