Pain is a fundamental biological response to noxious stimuli, comprising both unpleasant physical perceptions and negative emotions. It signals actual or potential tissue damage, and elicits protective responses needed for survival, such as withdrawal (1). There is profound interindividual variability in the response to noxious stimuli, susceptibility to pain, and the response to analgesics. This chapter will review the genetic factors that influence pain and sensitivity, and the response to drugs for acute and chronic pain therapy. Issues associated with analgesics, such as tolerance, dependence, and withdrawal, will not be addressed. Significant advances in understanding the neurobiology of pain have been made using genetic models (1). This chapter will focus on human pain and analgesia.

General anesthesia, whose goal is to render a patient insensitive to pain and control physiologic responses in the perioperative period, has as its two most basic elements analgesia and hypnosis (“sleep”). Nevertheless, a typical anesthetic comprises drugs from numerous classes, including benzodiazepine anxiolytics, sedative-hypnotics, inhalation anesthetics, opioids, muscle relaxants and their antagonists, and cardiovascular/vasoactive drugs (so-called balanced anesthesia). This chapter will also review the genetic factors that influence the response to anesthetics, with a focus on drug classes not covered in other chapters. Because opioids are central to both anesthesia and pain therapy, these will be a central focus. It is instructive to note that the field of pharmacogenetics had its birth in anesthesiology, with the discovery by Werner Kalow of heritable responses to the muscle relaxant succinylcholine (2, 3).