ArticleThe EMBO journal2018
Membrane cholesterol depletion as a trigger of Nav1.9 channel-mediated inflammatory pain.
Article in The EMBO journal, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 70 citations in OpenAlex.
- Piezo1 in Peripheral and Central Sensitisation: Implications for Chronic Pain.Bioengineering (Basel, Switzerland) · 2026Review
- Sequential membrane remodeling by cholesterol distinctly modulates HCN channels in naïve and neuropathic DRG neurons.The Journal of general physiology · 2026Article
- C-1101 multi-protein platelet and plasma-derived therapeutic to treat chronic lumbosacral radiculopathy.Frontiers in bioengineering and biotechnology · 2026Article
- Modulation of ion channels as emerging therapeutic targets in the treatment of diabetic neuropathy.EXCLI journal · 2026Review
- The NaV1.5 auxiliary subunit FGF13 modulates channels by regulating membrane cholesterol independent of channel binding.The Journal of clinical investigation · 2025Article
- Sepsis-induced hypocholesterolemia is linked to low cardiomyocyte membrane cholesterol and impaired catecholamine responsiveness.Critical care (London, England) · 2025Observational
- PCSK9 deficiency promotes the development of peripheral neuropathy.JCI insight · 2025Article
- A robust expression system reveals distinct gating mechanisms and calmodulin regulation of NaScience advances · 2025Article
- Nav1.8 and Chronic Pain: From Laboratory Animals to Clinical Patients.Biomolecules · 2025Review
- Elevated SCN11A concentrations associated with lower serum lipid levels in patients with major depressive disorder.Translational psychiatry · 2024Article
- Article
- Bidirectional Longitudinal Association between Back Pain and Loneliness in Later Life: Evidence from English Longitudinal Study of Ageing.Annals of geriatric medicine and research · 2024Article
- Article
- Predicting the Mechanism of Tiannanxing-shengjiang Drug Pair in Treating Pain Using Network Pharmacology and Molecular Docking Technology.Current computer-aided drug design · 2024Article
- The influence of Nav1.9 channels on intestinal hyperpathia and dysmotility.Channels (Austin, Tex.) · 2023Review
- Role of Lysosomal Cholesterol in Regulating PI(4,5)PAdvances in experimental medicine and biology · 2023Article
- Obesity-Associated Neuropathy: Recent Preclinical Studies and Proposed Mechanisms.Antioxidants & redox signaling · 2022Review
- Stress and Pain. Predictive (Neuro)Pattern Identification for Chronic Back Pain: A Longitudinal Observational Study.Frontiers in medicine · 2022Article
- Elevated Expression and Activity of Sodium Leak Channel Contributes to Neuronal Sensitization of Inflammatory Pain in Rats.Frontiers in molecular neuroscience · 2021Article
- Membrane Cholesterol Is a Critical Determinant for Hippocampal Neuronal Polarity.Frontiers in molecular neuroscience · 2021Article
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cholesterol is a major lipid component of the mammalian plasma membrane. While much is known about its metabolism, its transport, and its role in atherosclerotic vascular disease, less is known about its role in neuronal pathophysiology. This study reveals an unexpected function of cholesterol in controlling pain transmission. We show that inflammation lowers cholesterol content in skin tissue and sensory DRG culture. Pharmacological depletion of cellular cholesterol entails sensitization of nociceptive neurons and promotes mechanical and thermal hyperalgesia through the activation of voltage-gated Nav1.9 channels. Inflammatory mediators enhance the production of reactive oxygen species and induce partitioning of Nav1.9 channels from cholesterol-rich lipid rafts to cholesterol-poor non-raft regions of the membrane. Low-cholesterol environment enhances voltage-dependent activation of Nav1.9 channels leading to enhanced neuronal excitability, whereas cholesterol replenishment reversed these effects. Consistently, we show that transcutaneous delivery of cholesterol alleviates hypersensitivity in animal models of acute and chronic inflammatory pain. In conclusion, our data establish that membrane cholesterol is a modulator of pain transmission and shed a new light on the relationship between cholesterol homeostasis, inflammation, and pain.
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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.