Pain is an increasing clinical challenge affecting about half the population, with a substantial number of people suffering daily intense pain. Such suffering can be linked to the dramatic rise in opioid use and associated deaths in the United States. There is a pressing need for new analgesics with limited side effects. Here, we summarize what we know about the genetics of pain and implications for drug development. We make the case that chronic pain is not one but a set of disease states, with peripheral drive a key element in most. We argue that understanding redundancy and plasticity, hallmarks of the nervous system, is critical in developing analgesic drug strategies. We describe the exploitation of monogenic pain syndromes and genetic association studies to define analgesic targets, as well as issues associated with animal models of pain. We appraise present-day screening technologies and describe recent approaches to pain treatment that hold promise.

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