Journal
PHARMACOLOGY & THERAPEUTICS
Volume 124, Issue 2, Pages 168-184Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.pharmthera.2009.06.010
Keywords
Pharmacogenetics; Pain; Personalized therapy; Opioids; Non-opioid analgesics
Categories
Funding
- Wilhelm Sander Foundation [2006.111.1]
- Bundesministerium fur Bildung und Forschung [BMBF 01EM0511]
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Inadequately treated acute and chronic pain remains a major cause of suffering and dissatisfaction in pain therapy. A cause for the variable success of pharmacologic pain therapy is the different genetic disposition of patients to develop pain or to respond to analgesics. The patient's phenotype may be regarded as the result of synergistic or antagonistic effects of several genetic variants concomitantly present in an individual. Variants modulate the risk of developing painful disease or its clinical course (e.g., migraine, fibromyalgia, low back pain). Other variants modulate the perception of pain (e.g., OPRM1 or GCH1 variants conferring modest pain protection by increasing the tone of the endogenous opioid system or decreasing nitric oxide formation). Other polymorphisms alter pharmacokinetic mechanisms controlling the local availability of active analgesic molecules at their effector sites (e.g., decreased CYP2D6 related prodrug activation of codeine to morphine). In addition, genetic variants may alter pharmacodynamic mechanisms controlling the interaction of the analgesic molecules with their target structures (e.g., opioid receptor mutations). Finally, opioid dosage requirements may be increased depending on the risk of drug addiction (e.g., DRD2 polymorphisms decreasing the functioning of the dopaminergic reward system). With the complex nature of pain involving various mechanisms of nociception. drug action, drug pharmacology, pain disease and possibly substance addiction, a multigenic or even genome wide approach to genetics could be required to base individualized pain therapy on the patient's genotype. (C) 2009 Elsevier Inc. All rights reserved.
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