ArticlePain2018
Rare NaV1.7 variants associated with painful diabetic peripheral neuropathy.
Article in Pain, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers, 3 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
63 citing papers in PubMed, 3 syntheses or guidelines pooled it, 135 citations in OpenAlex.
- Prevalence and risk factors for painful diabetic peripheral neuropathy: a systematic review and meta-analysis.Frontiers in neurology · 2025Pooled it
- Association of Genetic Variant at Chromosome 12q23.1 With Neuropathic Pain Susceptibility.JAMA network open · 2021Pooled it
- Pharmacotherapeutic Options for Managing Neuropathic Pain: A Systematic Review and Meta-Analysis.Pain research & management · 2021Pooled it
- Polygenic risk scores indicates genetic overlap between peripheral pain syndromes and chronic postsurgical pain.Neurogenetics · 2020Trial
- Paeoniflorin as a candidate disease-modifying therapy for diabetic peripheral neuropathy: mechanisms, exposure challenges, and translational priorities.Frontiers in pharmacology · 2026Review
- Article
- Bibliometric Analysis: Insights Into the Podiatric Medicine Landscape of Diabetic Sensory Peripheral Neuropathy and Genomics.Journal of foot and ankle research · 2025Article
- Review
- Diabetic neuropathy: cutting-edge research and future directions.Signal transduction and targeted therapy · 2025Review
- Pain profiles and variability in temporal summation of pain and conditioned pain modulation in pain-free individuals and patients with low back pain, osteoarthritis, and fibromyalgia.European journal of pain (London, England) · 2025Article
- Small-Fiber Neuropathy: An Etiology-Oriented Review.Brain sciences · 2025Review
- Genetic Variants Influence the Development of Diabetic Neuropathy.International journal of molecular sciences · 2024Review
- Rbfox1 regulates alternative splicing of Nrcam in primary sensory neurons to mediate peripheral nerve injury-induced neuropathic pain.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2024Article
- Neanderthal introgression in SCN9A impacts mechanical pain sensitivity.Communications biology · 2023Article
- New perspectives in diabetic neuropathy.Neuron · 2023Review
- Genetic Profiling of Sodium Channels in Diabetic Painful and Painless and Idiopathic Painful and Painless Neuropathies.International journal of molecular sciences · 2023Article
- Peripheral mechanisms of peripheral neuropathic pain.Frontiers in molecular neuroscience · 2023Review
- Investigating genotype-phenotype relationship of extreme neuropathic pain disorders in a UK national cohort.Brain communications · 2023Article
- Nav1.7 is required for normal C-low threshold mechanoreceptor function in humans and mice.Brain : a journal of neurology · 2022Article
- TRP channels: a journey towards a molecular understanding of pain.Nature reviews. Neuroscience · 2022Review
3 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 5 institutions in 2 countries.
Funding
Abstract
Diabetic peripheral neuropathy (DPN) is a common disabling complication of diabetes. Almost half of the patients with DPN develop neuropathic pain (NeuP) for which current analgesic treatments are inadequate. Understanding the role of genetic variability in the development of painful DPN is needed for improved understanding of pain pathogenesis for better patient stratification in clinical trials and to target therapy more appropriately. Here, we examined the relationship between variants in the voltage-gated sodium channel NaV1.7 and NeuP in a deeply phenotyped cohort of patients with DPN. Although no rare variants were found in 78 participants with painless DPN, we identified 12 rare NaV1.7 variants in 10 (out of 111) study participants with painful DPN. Five of these variants had previously been described in the context of other NeuP disorders and 7 have not previously been linked to NeuP. Those patients with rare variants reported more severe pain and greater sensitivity to pressure stimuli on quantitative sensory testing. Electrophysiological characterization of 2 of the novel variants (M1852T and T1596I) demonstrated that gain of function changes as a consequence of markedly impaired channel fast inactivation. Using a structural model of NaV1.7, we were also able to provide further insight into the structural mechanisms underlying fast inactivation and the role of the C-terminal domain in this process. Our observations suggest that rare NaV1.7 variants contribute to the development NeuP in patients with DPN. Their identification should aid understanding of sensory phenotype, patient stratification, and help target treatments effectively.
Indexed as
Identifiers
What OpenQuestion holds
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.