ArticlePain2015
COMT gene locus: new functional variants.
Article in Pain, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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
19 citing papers in PubMed, 38 citations in OpenAlex.
- Influence of botulinum toxin A in pain perception and condyle-fossa relationship after the management of temporomandibular dysfunction: a randomized controlled clinical trial.Oral and maxillofacial surgery · 2024Trial
- The Role of Clinical Pharmacogenetics and Opioid Interactions in Pain Management: Current Evidence and Future Perspectives.Pharmaceutics · 2026Review
- Modeling Pain Without Injury: Inherited Rodent Models as Mechanistic Windows into Chronic Pain.Function (Oxford, England) · 2025Review
- Review
- Gene-Environment Interactions in Irrational Beliefs: The Roles of Childhood Adversity and Multiple Candidate Genes.International journal of molecular sciences · 2024Article
- Burning Mouth Syndrome and Hypertension: Prevalence, Gender Differences and Association with Pain and Psycho-Social Characteristics-A Case Control Study.International journal of environmental research and public health · 2023Article
- Heart rate variability responses to cognitive stress in fibromyalgia are characterised by inadequate autonomous system stress responses: a clinical trial.Scientific reports · 2023Article
- Preclinical orofacial pain assays and measures and chronic primary orofacial pain research: where we are and where we need to go.Frontiers in pain research (Lausanne, Switzerland) · 2023Review
- A Newly Synthesized Flavone from Luteolin Escapes from COMT-Catalyzed Methylation and Inhibits Lipopolysaccharide-Induced Inflammation in RAW264.7 Macrophages via JNK, p38 and NF-κB Signaling Pathways.Journal of microbiology and biotechnology · 2022Article
- Chronic persistent surgical pain is strongly associated with COMT alleles in patients undergoing cardiac surgery with median sternotomy.General thoracic and cardiovascular surgery · 2020Article
- Review
- Developmental Expression of SULT1C4 Transcript Variants in Human Liver: Implications for Discordance Between SULT1C4 mRNA and Protein Levels.Drug metabolism and disposition: the biological fate of chemicals · 2020Article
- Contribution of COMT and BDNF Genotype and Expression to the Risk of Transition From Acute to Chronic Low Back Pain.The Clinical journal of pain · 2020Article
- Bruxism Throughout the Lifespan and Variants inJournal of personalized medicine · 2020Article
- Biomarkers in Temporomandibular Disorder and Trigeminal Neuralgia: A Conceptual Framework for Understanding Chronic Pain.Canadian journal of pain = Revue canadienne de la douleur · 2020Article
- Potential Impact ofJournal of cardiovascular development and disease · 2018Article
- Interspecies comparison in the COMT-mediated methylation of 3-BTD.RSC advances · 2018Article
- Comorbidity of Alcohol Use Disorder and Chronic Pain: Genetic Influences on Brain Reward and Stress Systems.Alcoholism, clinical and experimental research · 2017Review
- Association of single nucleotide polymorphisms of ABCB1, OPRM1 and COMT with pain perception in cancer patients.Journal of Huazhong University of Science and Technology. Medical sciences = Hua zhong ke ji da xue xue bao. Yi xue Ying De wen ban = Huazhong keji daxue xuebao. Yixue Yingdewen ban · 2015Article
Corrections and comments
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Authors and funding
21 authors at 1 institution in 2 countries.
Funding
Abstract
Catechol-O-methyltransferase (COMT) metabolizes catecholaminergic neurotransmitters. Numerous studies have linked COMT to pivotal brain functions such as mood, cognition, response to stress, and pain. Both nociception and risk of clinical pain have been associated with COMT genetic variants, and this association was shown to be mediated through adrenergic pathways. Here, we show that association studies between COMT polymorphic markers and pain phenotypes in 2 independent cohorts identified a functional marker, rs165774, situated in the 3' untranslated region of a newfound splice variant, (a)-COMT. Sequence comparisons showed that the (a)-COMT transcript is highly conserved in primates, and deep sequencing data demonstrated that (a)-COMT is expressed across several human tissues, including the brain. In silico analyses showed that the (a)-COMT enzyme features a distinct C-terminus structure, capable of stabilizing substrates in its active site. In vitro experiments demonstrated not only that (a)-COMT is catalytically active but also that it displays unique substrate specificity, exhibiting enzymatic activity with dopamine but not epinephrine. They also established that the pain-protective A allele of rs165774 coincides with lower COMT activity, suggesting contribution to decreased pain sensitivity through increased dopaminergic rather than decreased adrenergic tone, characteristic of reference isoforms. Our results provide evidence for an essential role of the (a)-COMT isoform in nociceptive signaling and suggest that genetic variations in (a)-COMT isoforms may contribute to individual variability in pain phenotypes.
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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.