ArticlePain2019
Genetic mapping in Diversity Outbred mice identifies a Trpa1 variant influencing late-phase formalin response.
Article in Pain, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
What it found
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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.
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Who cites it
17 citing papers in PubMed, 30 citations in OpenAlex.
- Contrasting the genetic architecture of cardiac glutathione against other organs: unveiling a unique tissue-specific locus.Mammalian genome : official journal of the International Mammalian Genome Society · 2026Article
- Genetic correlation-guided mega-analysis of DO mice provides mechanistic insight and candidate genes for age-related pathologies.PLoS genetics · 2026Article
- Fifteen years of the Diversity Outbred mouse model: a review.Mammalian genome : official journal of the International Mammalian Genome Society · 2026Review
- Histone Lactylation Contributes to Neuropathic Pain by Facilitating mThe Journal of neuroscience : the official journal of the Society for Neuroscience · 2026Article
- Identification of novel genetic loci and candidate genes for progressive ethanol consumption in diversity outbred mice.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2024Article
- HBB contributes to individualized aconitine-induced cardiotoxicity in mice via interfering with ABHD5/AMPK/HDAC4 axis.Acta pharmacologica Sinica · 2024Article
- NAG-1/GDF-15 Transgenic Female Mouse Shows Delayed Peak Period of the Second Phase Nociception in Formalin-induced Inflammatory Pain.Experimental neurobiology · 2023Article
- An interaction of inorganic arsenic exposure with body weight and composition on type 2 diabetes indicators in Diversity Outbred mice.Mammalian genome : official journal of the International Mammalian Genome Society · 2022Article
- Article
- INFIMA leverages multi-omics model organism data to identify effector genes of human GWAS variants.Genome biology · 2021Article
- Diversity Outbred Mice Reveal the Quantitative Trait Locus and Regulatory Cells of HER2 Immunity.Journal of immunology (Baltimore, Md. : 1950) · 2020Article
- Genetic variation regulates opioid-induced respiratory depression in mice.Scientific reports · 2020Article
- C57BL/6 substrain differences in formalin-induced pain-like behavioral responses.Behavioural brain research · 2020Article
- TRPA1 gene variants hurting our feelings.Pflugers Archiv : European journal of physiology · 2020Review
- Review
- High-Diversity Mouse Populations for Complex Traits.Trends in genetics : TIG · 2019Review
- Article
Corrections and comments
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Authors and funding
14 authors at 2 institutions in 1 country.
Funding
Abstract
Identification of genetic variants that influence susceptibility to pain is key to identifying molecular mechanisms and targets for effective and safe therapeutic alternatives to opioids. To identify genes and variants associated with persistent pain, we measured late-phase response to formalin injection in 275 male and female Diversity Outbred mice genotyped for over 70,000 single nucleotide polymorphisms. One quantitative trait locus reached genome-wide significance on chromosome 1 with a support interval of 3.1 Mb. This locus, Nociq4 (nociceptive sensitivity quantitative trait locus 4; MGI: 5661503), harbors the well-known pain gene Trpa1 (transient receptor potential cation channel, subfamily A, member 1). Trpa1 is a cation channel known to play an important role in acute and chronic pain in both humans and mice. Analysis of Diversity Outbred founder strain allele effects revealed a significant effect of the CAST/EiJ allele at Trpa1, with CAST/EiJ carrier mice showing an early, but not late, response to formalin relative to carriers of the 7 other inbred founder alleles (A/J, C57BL/6J, 129S1/SvImJ, NOD/ShiLtJ, NZO/HlLtJ, PWK/PhJ, and WSB/EiJ). We characterized possible functional consequences of sequence variants in Trpa1 by assessing channel conductance, TRPA1-TRPV1 interactions, and isoform expression. The phenotypic differences observed in CAST/EiJ relative to C57BL/6J carriers were best explained by Trpa1 isoform expression differences, implicating a splice junction variant as the causal functional variant. This study demonstrates the utility of advanced, high-precision genetic mapping populations in resolving specific molecular mechanisms of variation in pain sensitivity.
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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.