Related Experiment Video
Updated: Feb 26, 2026
Assessment of Morphine-induced Hyperalgesia and Analgesic Tolerance in Mice Using Thermal and Mechanical Nociceptive Modalities
Published on: July 29, 2014
Review of Opioid Pharmacogenetics and Considerations for Pain Management
Aniwaa Owusu Obeng1,2,3, Issam Hamadeh4, Michael Smith5
1The Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY.
Abstract:
Opioid analgesics are the standards of care for the treatment of moderate to severe nociceptive pain, particularly in the setting of cancer and surgery. Their analgesic properties mainly emanate from stimulation of the μ receptors, which are encoded by the OPRM1 gene. Hepatic metabolism represents the major route of elimination, which, for some opioids, namely codeine and tramadol, is necessary for their bioactivation into more potent analgesics. The highly polymorphic nature of the genes coding for phase I and phase II enzymes (pharmacokinetics genes) that are involved in the metabolism and bioactivation of opioids suggests a potential interindividual variation in their disposition and, most likely, response. In fact, such an association has been substantiated in several pharmacokinetic studies described in this review, in which drug exposure and/or metabolism differed significantly based on the presence of polymorphisms in these pharmacokinetics genes. Furthermore, in some studies, the observed variability in drug exposure translated into differences in the incidence of opioid-related adverse effects, particularly nausea, vomiting, constipation, and respiratory depression. Although the influence of polymorphisms in pharmacokinetics genes, as well as pharmacodynamics genes (OPRM1 and COMT) on response to opioids has been a subject of intense research, the results have been somehow conflicting, with some evidence insinuating for a potential role for OPRM1. The Clinical Pharmacogenetics Implementation Consortium guidelines provide CYP2D6-guided therapeutic recommendations to individualize treatment with tramadol and codeine. However, implementation guidelines for other opioids, which are more commonly used in real-world settings for pain management, are currently lacking. Hence, further studies are warranted to bridge this gap in our knowledge base and ultimately ascertain the role of pharmacogenetic markers as predictors of response to opioid analgesics.
Insights
Genetic variations in how the body processes opioids affect pain relief and side effects. Understanding these pharmacogenetic markers could personalize pain management, but more research is needed for common opioids.
Area of Science:
- Pharmacogenetics
- Pain Management
- Drug Metabolism
Background:
- Opioid analgesics are standard for moderate-to-severe pain, acting via μ receptors (OPRM1 gene).
- Hepatic metabolism is crucial for opioid elimination and bioactivation (e.g., codeine, tramadol).
- Genetic polymorphisms in metabolic enzymes (pharmacokinetics genes) can cause interindividual variability in opioid response.
Purpose of the Study:
- To review the association between pharmacogenetic variations and opioid disposition, efficacy, and adverse effects.
- To identify gaps in current pharmacogenetic knowledge for opioid analgesics.
- To highlight the need for further research to guide clinical implementation.
Main Methods:
- Review of pharmacokinetic and pharmacodynamic studies on opioid analgesics.
- Analysis of the impact of genetic polymorphisms in drug-metabolizing enzymes and opioid receptors.
- Examination of existing clinical pharmacogenetics guidelines.
Main Results:
- Significant interindividual differences in drug exposure and metabolism linked to pharmacokinetics gene polymorphisms.
- Variability in drug exposure correlated with differences in opioid-related adverse effects.
- Conflicting results regarding the influence of OPRM1 and COMT polymorphisms on opioid response.
Conclusions:
- Pharmacogenetic markers show potential for predicting opioid response and guiding personalized pain management.
- Current guidelines primarily focus on codeine and tramadol (CYP2D6-guided).
- Further research is essential to develop implementation guidelines for widely used opioids and fully utilize pharmacogenetic predictors.
Related Concept Videos
01:25Analgesia and Pain Management
01:20Opioid Analgesics: Morphine and Other Natural Cogeners
01:15Opioid Analgesics: Synthetic and Semisynthetic Opioids
01:29Pharmacogenetics and Pharmacogenomics: Overview
01:22Opioid Receptors: Overview
01:29Pharmacogenetic Phenotypes: Alterations in Pharmacokinetics, Drug Targets and Biologic Milieu