Abstract
This paper reviews the impact of genetic variability of drug metabolizing enzymes, transporters, receptors, and pathways involved in chronic pain perception on the efficacy and safety of analgesics and other drugs used for chronic pain treatment. Several candidate genes have been identified in the literature, while there is usually only limited clinical evidence substantiating for the penetration of the testing for these candidate biomarkers into the clinical practice. Further, the pain-perception regulation and modulation are still not fully understood, and thus more complex knowledge of genetic and epigenetic background for analgesia will be needed prior to the clinical use of the candidate genetic biomarkers.
Highlights
It is well recognized that pain perception as well as pain relief after analgesic treatment display, large interindividual variability in the population that affects selection of analgesics and their dosing in the population
CYP2D6 accounts for 2–5% of the total hepatic P450 enzymes; it is involved in the metabolism of 25% of all drugs administered in clinical practice [47]
The adverse outcomes of codeine treatment could be avoided and the safety of pain management could be improved by CYP2D6 genetic testing before prescribing the drug or by using alternative analgesics [156]
Summary
It is well recognized that pain perception as well as pain relief after analgesic treatment display, large interindividual variability in the population that affects selection of analgesics and their dosing in the population. Gender, ethnicity, and actual level of stress, mood, or diseases may modify individual pain perception. This alters the response to drug treatment, which represents a complex interaction between analgesic medication and organism. Several mechanisms may be involved in the pain relief either as drug targets or as drug metabolizing enzymes/transporters, and the genetic variability in these processes influence the analgesic efficacy in individual patients. This review is focused on highlighting the genetic variability reported to affect chronic pain treatment efficacy. This paper does not provide exhaustive list of polymorphisms reported but focuses on the current status of the most recognized pharmacogenetic areas and variables in the treatment of chronic pain
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