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This may reflect variability in the function of the molecular target of the drug, or in the pathophysiologic context in which the drug interacts with its receptor-target e. With growing public concern over intraoperative awareness, understanding the mechanisms responsible for this variability may facilitate implementation of patient-specific preventative strategies. Genetic Variability in Pain Response Similar to the observed variability in anesthetic potency, the response to painful stimuli and analgesic manipulations varies among individuals. Increasing evidence suggests that pain behavior in response to noxious stimuli and its modulation by the central nervous system in response to drug administration or environmental stress, as well as the development of persistent pain conditions through pain amplification, are strongly influenced by genetic factors. Various strains of knockout mice lacking target genes like neurotrophins and their receptors e. In addition to the genetic control of peripheral nociceptive pathways, considerable evidence exists for genetic variability in the descending central pain modulatory pathways, further explaining the interindividual variability in analgesic responsiveness. Although such genetic variation in drug metabolizing enzymes or drug targets usually result in unusually variable drug response, genetic markers associated with rare but life-threatening side effects have also been described.

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