ArticlePLoS genetics2012
Genes contributing to pain sensitivity in the normal population: an exome sequencing study.
Article in PLoS genetics, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 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.
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Who cites it
27 citing papers in PubMed, 64 citations in OpenAlex.
- Evaluation of the effectiveness of local anesthesia approaches for symptomatic irreversible pulpitis: a systematic review and meta-analysis.Frontiers in dental medicine · 2025Review
- Quantitative sensory testing and chronic pain syndromes: a cross-sectional study from TwinsUK.BMJ open · 2024Article
- Accurate phenotypic classification and exome sequencing allow identification of novel genes and variants associated with adult-onset hearing loss.PLoS genetics · 2023Article
- Sodium-calcium exchanger-3 regulates pain "wind-up": From human psychophysics to spinal mechanisms.Neuron · 2022Article
- Article
- Baroreceptor Modulation of the Cardiovascular System, Pain, Consciousness, and Cognition.Comprehensive Physiology · 2021Article
- Current Treatment Options for Intervertebral Disc Pathologies.Cartilage · 2020Article
- Mechanisms Challenges of the Pain Phenomenon.Frontiers in pain research (Lausanne, Switzerland) · 2020Article
- Cytotoxic Immunity in Peripheral Nerve Injury and Pain.Frontiers in neuroscience · 2020Review
- Article
- Review
- Clinical Perspective on Pain and Pain Phenotypes in Osteoarthritis.Current rheumatology reports · 2018Review
- Association of the resolvin precursor 17-HDHA, but not D- or E- series resolvins, with heat pain sensitivity and osteoarthritis pain in humans.Scientific reports · 2017Article
- Altered white matter microarchitecture in the cingulum bundle in women with primary dysmenorrhea: A tract-based analysis study.Human brain mapping · 2017Article
- Heat pain detection threshold is associated with the area of secondary hyperalgesia following brief thermal sensitization: a study of healthy male volunteers.Journal of pain research · 2017Article
- Experimental pain phenotyping in community-dwelling individuals with knee osteoarthritis.Pain · 2016Article
- Neuropathic pain as part of chronic widespread pain: environmental and genetic influences.Pain · 2015Article
- Article
- Association of ADRB1 gene polymorphisms with pain sensitivity in a Chinese population.International journal of clinical and experimental medicine · 2015Article
- A rare variant in APOC3 is associated with plasma triglyceride and VLDL levels in Europeans.Nature communications · 2014Article
Corrections and comments
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Authors and funding
27 authors at 6 institutions in 4 countries.
Funding
Abstract
Sensitivity to pain varies considerably between individuals and is known to be heritable. Increased sensitivity to experimental pain is a risk factor for developing chronic pain, a common and debilitating but poorly understood symptom. To understand mechanisms underlying pain sensitivity and to search for rare gene variants (MAF<5%) influencing pain sensitivity, we explored the genetic variation in individuals' responses to experimental pain. Quantitative sensory testing to heat pain was performed in 2,500 volunteers from TwinsUK (TUK): exome sequencing to a depth of 70× was carried out on DNA from singletons at the high and low ends of the heat pain sensitivity distribution in two separate subsamples. Thus in TUK1, 101 pain-sensitive and 102 pain-insensitive were examined, while in TUK2 there were 114 and 96 individuals respectively. A combination of methods was used to test the association between rare variants and pain sensitivity, and the function of the genes identified was explored using network analysis. Using causal reasoning analysis on the genes with different patterns of SNVs by pain sensitivity status, we observed a significant enrichment of variants in genes of the angiotensin pathway (Bonferroni corrected p = 3.8×10(-4)). This pathway is already implicated in animal models and human studies of pain, supporting the notion that it may provide fruitful new targets in pain management. The approach of sequencing extreme exome variation in normal individuals has provided important insights into gene networks mediating pain sensitivity in humans and will be applicable to other common complex traits.
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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.