ArticleBrain : a journal of neurology2018
A novel human pain insensitivity disorder caused by a point mutation in ZFHX2.
Article in Brain : a journal of neurology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers, 1 of them a synthesis that pooled it.
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Who cites it
24 citing papers in PubMed, 1 synthesis or guideline pooled it, 50 citations in OpenAlex.
- Transcriptomic Studies of Antidepressant Action in Rodent Models of Depression: A First Meta-Analysis.International journal of molecular sciences · 2022Pooled it
- Gene variants associated with pediatric-onset erythromelalgia: Mendelian and rare-variant association analyses.Pain reports · 2026Article
- A conserved C. elegans zinc finger homeodomain protein, ZFH-2, is continuously required for the structural integrity and function of the alimentary tract and gonad.Development (Cambridge, England) · 2026Article
- A conservedbioRxiv : the preprint server for biology · 2026Article
- A pathological missense mutation in the deubiquitinase USP5 leads to insensitivity to pain.The Journal of experimental medicine · 2025Article
- Re-analysis of single cell and spatial transcriptomics data reveals B cell landscape in gastric cancer microenvironment and its potential crosstalk with tumor cells for clinical prognosis.Journal of translational medicine · 2024Article
- Homozygosity for a RareInternational journal of molecular sciences · 2024Article
- Pathology of pain and its implications for therapeutic interventions.Signal transduction and targeted therapy · 2024Review
- Identifying circRNA-miRNA-mRNA Regulatory Networks in Chemotherapy-Induced Peripheral Neuropathy.Current issues in molecular biology · 2023Article
- Molecular Mimicry and HLA Polymorphisms May Drive Autoimmunity in Recipients of the BNT-162b2 mRNA Vaccine: A Computational Analysis.Microorganisms · 2023Article
- Gpr83 Tunes Nociceptor Function, Controlling Pain.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2023Article
- Genetic pain loss disorders.Nature reviews. Disease primers · 2022Review
- Assessing the impact of pain-linked Nav1.7 variants: An example of two variants with no biophysical effect.Channels (Austin, Tex.) · 2021Article
- Early life stress and LPS interact to modify the mouse cortical transcriptome in the neonatal period.Brain, behavior, & immunity - health · 2021Article
- The development of somatosensory neurons: Insights into pain and itch.Current topics in developmental biology · 2021Review
- Understanding the genetic basis of congenital insensitivity to pain.British medical bulletin · 2020Review
- Sensory neuron-derived NaScience advances · 2020Article
- Vitamin D and Its Potential Interplay With Pain Signaling Pathways.Frontiers in immunology · 2020Review
- Association of G472A allele of membrane bound catechol-O-methyltransferase gene with chronic post-sternotomy pain.General thoracic and cardiovascular surgery · 2019Article
- A catalog of single nucleotide changes distinguishing modern humans from archaic hominins.Scientific reports · 2019Article
Corrections and comments
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Authors and funding
33 authors at 5 institutions in 5 countries.
Funding
Abstract
Chronic pain is a major global public health issue causing a severe impact on both the quality of life for sufferers and the wider economy. Despite the significant clinical burden, little progress has been made in terms of therapeutic development. A unique approach to identifying new human-validated analgesic drug targets is to study rare families with inherited pain insensitivity. Here we have analysed an otherwise normal family where six affected individuals display a pain insensitive phenotype that is characterized by hyposensitivity to noxious heat and painless bone fractures. This autosomal dominant disorder is found in three generations and is not associated with a peripheral neuropathy. A novel point mutation in ZFHX2, encoding a putative transcription factor expressed in small diameter sensory neurons, was identified by whole exome sequencing that segregates with the pain insensitivity. The mutation is predicted to change an evolutionarily highly conserved arginine residue 1913 to a lysine within a homeodomain. Bacterial artificial chromosome (BAC) transgenic mice bearing the orthologous murine p.R1907K mutation, as well as Zfhx2 null mutant mice, have significant deficits in pain sensitivity. Gene expression analyses in dorsal root ganglia from mutant and wild-type mice show altered expression of genes implicated in peripheral pain mechanisms. The ZFHX2 variant and downstream regulated genes associated with a human pain-insensitive phenotype are therefore potential novel targets for the development of new analgesic drugs.awx326media15680039660001.
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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.