Pharmacogenetics of chronic pain management
Objective: The experience of chronic pain is one of the commonest reasons individuals seek medical attention, making the management of chronic pain a major issue in clinical practice. Drug metabolism and responses are affected bymany factors,with genetic variations offering only a partial explanation of an individual’s response. There is a paucity of evidence for the benefits of pharmacogenetic testing in the context of pain management.
Design andmethods: We reviewed the literature between 2000 and 2013, and references cited therein, using various keywords related to pain management, pharmacology and pharmacogenetics.
Results: Opioids continue to be themainstay of chronic painmanagement. Several non-opioid based therapies, such as treatment with cannabinoids, gene therapy and epigenetic-based approaches are now available for these patients. Adjuvant therapies with antidepressants, benzodiazepines or anticonvulsants can also be useful in managing pain. Currently, laboratory monitoring of pain management patients, if performed, is largely through urine drug measurements.
Conclusions: Drug half-life calculations can be used as functionalmarkers of the cumulative effect of pharmacogenetics and drug–drug interactions. Assessment of half-life and therapeutic effects may bemore useful than genetic testing in preventing adverse drug reactions to pain medications, while ensuring effective analgesia. Definitive, mass spectrometry-based methods, capable of measuring parent drug and metabolite levels, are the most useful assays for this purpose. Urine drug measurements do not necessarily correlate with serum drug concentrations or therapeutic effects. Therefore, they are limited in their use in monitoring efficacy and toxicity.
© 2014 The Authors. The Canadian Society of Clinical Chemists. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license.
According to the International Association for the Study of Pain (IASP), pain is defined as an “unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage”. Several different subtypes of pain can be described, based on their neuropsychological basis and duration, including neuropathic, nociceptive, psychogenic, referred, phantom, acute and chronic. Chronic pain is very common, with one in three Americans and one in five Canadians reported to suffer from this problem. It is one of the most frequent reasons for individuals to seek medical care. If untreated, chronic pain can lead to physical and social dysfunction and diminished quality of life.
Successful pain management provides adequate analgesia without excessive adverse effects. Current pain management strategies largely employ the use of the World Health Organization (WHO) pain ladder, beginning with non-opioid medications, such as NSAIDs, progressing to weak opioids, and culminating with strong opioids, particularly in cancer pain. TheWHO also recommends adjuvant therapy with antidepressant medications to aid in reducing anxiety often associated with chronic pain.
Management of pain can be complicated by lack of adherence, the potential for abuse or dependence on the medications used and adverse drug side effects. Many factors can influence drug disposition, including genetic variation, which can further complicate management of these patients.
Genetic studies have identified several loci in which polymorphic changes can influence the pharmacodynamics and kinetics of analgesic drugs. Current patientmonitoring in pain management (if performed at all) is largely based on urine drugmeasurements. However, therapeutic drug monitoring (TDM) via plasma drug levels and half-life may prove more useful in monitoring patients prescribed pain medications to ensure efficacy while minimizing adverse drug reactions. TDM can also be very useful for the identification of drug-related side effects and patient-reported lack of effect (e.g., tolerance).
Finally, non-opioid analgesics are often tried as options for management of pain, particularly in individualswhere opioids are not a suitable choice. In addition, novel therapies, including targeting of epigenetic changes and gene therapy-based approaches are further broadening future options for the treatment of chronic pain.