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Genetic variability of pain perception and treatment—clinical pharmacological implications

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Abstract

Evidence of a genetic control of pain has led to efforts to exploit genotyping information from pain patients for the development of analgesics and for the selection of pharmacological approaches to pain. Research on translating the genetic bases of familial insensitivity to pain has contributed to the discovery of crucial molecular pathways of pain and to the identification of new analgesic targets (e.g., the Nav1.7 sodium channel, neurotrophic tyrosine kinase receptors, nerve growth factor). Moreover, human genetic variants leading to enhanced or reduced function of specific molecular pathways are employed as substitutes for the lack of modulator molecules usable in humans, enabling nociceptive or anti-nociceptive pathways in humans to be studied before drug development. Translational approaches have also been used to verify the importance of experimentally discovered pain pathways in humans, such as GTP cyclohydrolase 1 and the potassium channel Kv9.1. In addition to these uses of genetics as a research tool, an individualized pharmacological therapy based on the patient’s genotype has been attempted. In terms of analgesics in clinical use, such an approach is at the present time only marginally available. For future analgesic targeting, for example, Nav1.7 or TRPA1, the genotype may be the target of a selective cure for syndromes caused by increased-function mutations in the coding genes. The consideration of human genetics in drug studies may accelerate analgesic drug development while reducing cost because the clinical success may be partly anticipated by including information of functional genetic variants that mimic the action of future analgesics. These developments show that genotyping information obtained from studies on pain patients plays a role in the clinical pharmacology of pain.

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    Jörn Lötsch

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Lötsch, J. Genetic variability of pain perception and treatment—clinical pharmacological implications. Eur J Clin Pharmacol 67, 541–551 (2011). https://doi.org/10.1007/s00228-011-1012-9

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