ArticlePain2019
OPRM1 rs1799971, COMT rs4680, and FAAH rs324420 genes interact with placebo procedures to induce hypoalgesia.
Article in Pain, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers, 1 of them a synthesis 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
21 citing papers in PubMed, 1 synthesis or guideline pooled it, 48 citations in OpenAlex.
- Pooled it
- Is it personality or genes? - A secondary analysis on a randomized controlled trial investigating responsiveness to placebo analgesia.Scandinavian journal of pain · 2025Trial
- Trial
- Effects of Mu-Opiate Receptor Gene Polymorphism rs1799971 (A118G) on the Antidepressant and Dissociation Responses in Esketamine Nasal Spray Clinical Trials.The international journal of neuropsychopharmacology · 2020Trial
- Neural and behavioral changes driven by observationally-induced hypoalgesia.Scientific reports · 2019Trial
- Article
- Drug response is related to NR3C1 and FAAH polymorphism in Chinese pediatric epilepsy patients.Italian journal of pediatrics · 2025Article
- Clinical neuroscience and neurobiology of placebo and nocebo effects.International review of neurobiology · 2025Review
- Transcriptomic Profiles Associated with Experimental Placebo Effects in Chronic Pain.Clinical pharmacology and therapeutics · 2024Article
- Clinical Phenotypes Supporting the Relationship Between Sleep Disturbance and Impairment of Placebo Effects.The journal of pain · 2024Article
- Review
- Multimodal non-invasive non-pharmacological therapies for chronic pain: mechanisms and progress.BMC medicine · 2023Review
- The Biology of Placebo and Nocebo Effects on Experimental and Chronic Pain: State of the Art.Journal of clinical medicine · 2023Review
- Effects of placebo administration on immune mechanisms and relationships with central endogenous opioid neurotransmission.Molecular psychiatry · 2022Article
- A systems omics-based approach to decode substance use disorders and neuroadaptations.Neuroscience and biobehavioral reviews · 2021Review
- Cutoff criteria for the placebo response: a cluster and machine learning analysis of placebo analgesia.Scientific reports · 2021Article
- Genetic susceptibility of opioid receptor genes polymorphism to drug addiction: A candidate-gene association study.BMC psychiatry · 2021Article
- Optimizing Aggregated N-Of-1 Trial Designs for Predictive Biomarker Validation: Statistical Methods and Theoretical Findings.Frontiers in digital health · 2020Article
- Editorial: Placebo and Nocebo Effects in Psychiatry and Beyond.Frontiers in psychiatry · 2020Article
- Prior Therapeutic Experiences, Not Expectation Ratings, Predict Placebo Effects: An Experimental Study in Chronic Pain and Healthy Participants.Psychotherapy and psychosomatics · 2020Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
Genetics studies on the placebo hypoalgesic effect highlight a promising link between single nucleotide polymorphisms (SNPs) in the dopamine, opioid, and endocannabinoid genes and placebo hypoalgesia. However, epistasis and replication studies are missing. In this study, we expanded on previous findings related to the 3 SNPs in the opioid receptor mu subunit (OPRM1 rs1799971), catechol-O-methyltransferase (COMT rs4680), and fatty acid amide hydrolase (FAAH rs324420) genes associated with placebo hypoalgesia and tested the effect of a 3-way interaction on placebo hypoalgesia. Using 2 well-established placebo procedures (verbal suggestion and learning paradigm), we induced significant placebo hypoalgesic effects in 160 healthy participants. We found that individuals with OPRM1 AA combined with FAAH Pro/Pro and those carrying COMT met/met together with FAAH Pro/Pro showed significant placebo effects. Participants with COMT met/val alleles showed significant placebo effects independently of OPRM1 and FAAH allele combinations. Finally, the model that included the placebo procedure and genotypes predicted placebo responsiveness with a higher accuracy (area under the curve, AUC = 0.773) as compared to the SNPs alone indicating that genetic variants can only partially explain the placebo responder status. Our results suggest that the endogenous mu-opioid system with a larger activation in response to pain in the met/val allele carriers as well as the synergism between endogenous mu-opioid system and cannabinoids might play the most relevant role in driving hypoalgesic responses. Future epistasis studies with larger sample sizes will help us to fully understand the complexity of placebo effects and explain the mechanisms that underlie placebo responsiveness.
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.