Genetic variability and opioid efficacy

A number of clinical observations suggest that patients' genetic disposition influences their response to opioids. This position is strengthened because data from basic research agree with data obtained in human studies. However, a clinical relevance for genetic variability was only established for the CYP2D6 gene polymorphisms and the mu-opioid receptor gene A118G polymorphism. For other opioids or other candidate genes, clinical data are either not available or the data are yet too limited to reach a definitive conclusion. Still, the results obtained so far strongly indicate that opioid efficacy is related to inborn properties caused by genetic variability related to opioid metabolism, opioid receptors, opioid signaling, and opioid transporters. In addition, clinical effects are influenced by variations in other biological systems that modify the effects induced by opioid agonists. Clinical data are lacking for most opioids and little is known about the exact mechanisms by which genetic variability interacts with opioid signaling. Further research should combine basic and clinical research with the end goal of obtaining improved and individualized pain treatment.