ArticleMolecular pain2009
Genetic variation in the serotonin transporter gene (5-HTTLPR, rs25531) influences the analgesic response to the short acting opioid Remifentanil in humans.
Article in Molecular pain, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 75 citations in OpenAlex.
- Non-invasive combined surrogates of remifentanil blood concentrations with relevance to analgesia.Naunyn-Schmiedeberg's archives of pharmacology · 2013Trial
- Trial
- Conditioned pain modulation is associated with common polymorphisms in the serotonin transporter gene.PloS one · 2011Trial
- Perception of thermal pain and the thermal grill illusion is associated with polymorphisms in the serotonin transporter gene.PloS one · 2011Trial
- Opioid-Induced Hyperalgesia and Inflammaging in the Management of Spine Pain: The Case for Genetically Directed Dopamine Homeostasis.International journal of spine surgery · 2025Article
- Mechanisms of Remifentanil-Induced Postoperative Hyperalgesia: A Comprehensive Review.Drug design, development and therapy · 2025Review
- Serotonin Transporter (5-Hydroxytryptamine Transporter, SERT, SLC6A4) and Sodium-dependent Reuptake Inhibitors as Modulators of Pain Behaviors and Analgesic Responses.The journal of pain · 2024Review
- Developmental Dyslexia: Insights from EEG-Based Findings and Molecular Signatures-A Pilot Study.Brain sciences · 2024Article
- Effect of common OPRM1, COMT, SLC6A4, ABCB1, and CYP2B6 polymorphisms on perioperative analgesic and propofol demands on patients subjected to thyroidectomy surgery.Pharmacological reports : PR · 2023Article
- Mechanisms and implications in gene polymorphism mediated diverse reponses to sedatives, analgesics and muscle relaxants.Korean journal of anesthesiology · 2023Article
- Non-Peptide Opioids Differ in Effects on Mu-Opioid (MOP) and Serotonin 1A (5-HTMolecules (Basel, Switzerland) · 2022Article
- Article
- Novel associations betweenPharmacogenomics · 2021Observational
- Effects of Polymorphisms in the Serotonin Transporter Promoter-Linked Polymorphic Region on Postthoracotomy Pain Severity.Journal of pain research · 2021Article
- Pharmacogenomics of Pain Management: The Impact of Specific Biological Polymorphisms on Drugs and Metabolism.Current oncology reports · 2020Review
- Genetics of perioperative pain management.Current opinion in anaesthesiology · 2018Review
- Introducing Precision Addiction Management of Reward Deficiency Syndrome, the Construct That Underpins All Addictive Behaviors.Frontiers in psychiatry · 2018Article
- Article
- The pharmacogenomics of pain management: prospects for personalized medicine.Journal of pain research · 2016Review
- Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThere is evidence from animal studies that serotonin (5-HT) can influence the antinociceptive effects of opioids at the spinal cord level. Therefore, there could be an influence of genetic polymorphisms in the serotonin system on individual variability in response to opioid treatment of pain. The serotonin transporter (5-HTT) is a key regulator of serotonin metabolism and availability and its gene harbors several known polymorphisms that are known to affect 5-HTT expression (e.g. 5-HTTLPR, rs25531). The aim of this study was to investigate if the triallelic 5-HTTLPR influences pain sensitivity or the analgesic effect of opioids in humans. 43 healthy volunteers (12 men, 31 women, mean age 26 years) underwent heat pain stimulations before and after intravenous injection of Remifentanil; a rapid and potent opioid drug acting on micro-type receptors. Subjects rated their perceived pain on a visual analogue scale (VAS). All participants were genotyped for the 5-HTTLPR and the rs25531 polymorphism. We recruited by advertising, with no history of drug abuse, chronic pain or psychiatric disorders.
resultsAt baseline, there was no difference in pain ratings for the different triallelic 5-HTTLPR genotype groups. However, the opiod drug had a differential analgesic effect depending on the triallelic 5-HTTLPR genotype. Remifentanil had a significantly better analgesic effect in individuals with a genotype coding for low 5-HTT expression (SA/SA and SA/LG) as compared to those with high expression(LA/LA), p < 0.02. The analgesic effect for the three different genotype groups was linear to degree of 5-HTT expression.
conclusionThis is the first report showing an influence of the triallelic 5-HTTLPR on pain sensitivity or the analgesic effect of opioids in humans. Previously the 5-HTTLPR s-allele has been associated with higher risk of developing chronic pain conditions but in this study we show that the genotype coding for low 5-HTT expression is associated with a better analgesic effect of an opioid. The s-allele has been associated with downregulation of 5-HT1 receptors and we suggest that individuals with a desensitization of 5-HT1 receptors have an increased analgesic response to opioids during acute pain stimuli, but may still be at increased risk of developing chronic pain conditions.
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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.