Pharmacogenetics of chronic pain management


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3/14/2016
03:56 | Hannah Hoggarth
How is oxycodone metabolized
Pharmacogenetics of chronic pain management

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.

Acute and chronic are terms commonly used to describe the duration of painful sensations, but are difficult to categorically define. No articles found. In general, acute pain resolves within weeks of the initial causative insult, whereas chronic pain is continuous, long-term pain which can last months or years.

Pain is the most common presenting physical symptom in primary care, accounting for an enormous burden of patient suffering, quality of life, work and social disability, and health care and societal costs. Pain is defined as an unpleasant sensory and emotional experience associated with actual or potential tissue damage. However, the experience of pain is highly subjective and idiosyncratic, and individuals develop pain thresholds through experiences of injury or pathology in early life.

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Several different subtypes of pain can be described, based on their neuropsychological basis and duration, including neuropathic, nociceptive, psychogenic, referred, phantom, acute and chronic. 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”. Chronic pain is very common, with one in three Americans and one in five Canadians reported to suffer from this problem  and . If untreated, chronic pain can lead to physical and social dysfunction and diminished quality of life. It is one of the most frequent reasons for individuals to seek medical care.

Phantom pain, a sub-type of referred pain, is the feeling of painful sensations from a part of the body which has been lost, and from which the brain no longer receives signals. Referred pain is perceived at a site adjacent to or distant from the site of painful stimulus; the mechanism for this process is not yet well understood. Psychogenic pain refers to painful sensations caused or amplified by mental or emotional factors with no evident physical tissue damage. Individuals who have undergone limb amputation often experience phantom pain.

The mechanisms and enzymes involved in pain medications.

The abstracts of all papers were reviewed and those that appeared to be relevant to the subject were selected for further study. References cited therein, including original publications, were also selected for further review. Using the following headings: “pain management medications”, “pain management drugs”, “chronic pain management”, “pharmacogenetics and pain management”, and “drug monitoring and pain management”, we identified 6670 papers. We conducted an online systematic search for papers and related abstracts published between 2000 and 2013 using the National Library of Medicine database, PubMed.

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. There is a paucity of evidence for the benefits of pharmacogenetic testing in the context of pain management. Drug metabolism and responses are affected by many factors, with genetic variations offering only a partial explanation of an individual’s response.

The most common causes of chronic neuropathic pain include diabetic neuropathy, post-herpetic neuralgia, fibromyalgia, lower back pain (radiculopathy due to disc herniation) and osteoarthritis. Common descriptions accompanying neuropathic pain include “burning”, “shooting” or “shock-like” sensations. Neuropathic pain results from actual damage to nerve fibers themselves in the central or peripheral nervous system. This damage can lead to nerve dysfunction, causing numbness, weakness and/or loss of reflexes.

This article has not been cited. No articles found.

We reviewed the literature between 2000 and 2013, and references cited therein, using various keywords related to pain management, pharmacology and pharmacogenetics.

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. The WHO also recommends adjuvant therapy with antidepressant medications to aid in reducing anxiety often associated with chronic pain. Successful pain management provides adequate analgesia without excessive adverse effects.

Volume 47, Issues 13–14, September 2014, Pages 1169–1187.

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. Finally, non-opioid analgesics are often tried as options for management of pain, particularly in individuals where opioids are not a suitable choice.

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. Drug half-life calculations can be used as functional markers of the cumulative effect of pharmacogenetics and drug–drug interactions. Assessment of half-life and therapeutic effects may be more useful than genetic testing in preventing adverse drug reactions to pain medications, while ensuring effective analgesia. Therefore, they are limited in their use in monitoring efficacy and toxicity.

Pharmacogenetic and pharmacological properties of drugs used in the management of pain.

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. Several non-opioid based therapies, such as treatment with cannabinoids, gene therapy and epigenetic-based approaches are now available for these patients. Opioids continue to be the mainstay of chronic pain management.

It is often categorized as somatic (derived from skin and deep tissue) or visceral (originating from internal organs). Due to high concentrations of nociceptors in somatic tissues, chronic somatic pain is typically localized, and often results from degenerative or inflammatory processes. Nociceptive pain is frequently described as stabbing, pricking, burning, throbbing or cramping. Nociceptive pain is caused by stimulation of specialized sensory neurons, called nociceptors, by noxious stimuli including extremes of temperature, or mechanical or chemical excitation.

Current patient monitoring in pain management (if performed at all) is largely based on urine drug measurements. TDM can also be very useful for the identification of drug-related side effects and patient-reported lack of effect ( e.g., tolerance). Genetic studies have identified several loci in which polymorphic changes can influence the pharmacodynamics and kinetics of analgesic drugs. 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.

Pharmacogenetic of pain. • We review different types of pain.

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