A theoretical framework and nomenclature to characterize the iatrogenic contribution of therapeutic opioid exposure to opioid induced hyperalgesia, physical dependence, and opioid use disorder.

Opioid use, misuse, and risky use contribute to a critically important and complex crisis in current healthcare. Consequences of long-term opioid use, including opioid induced hyperalgesia, physical dependence, and opioid use disorder, can be considered iatrogenic, or partially iatrogenic, in cases where therapeutic opioid exposures were contributory. Research investigation and presumptive clinical action are needed to attenuate the iatrogenic component of the opioid crisis; treatment of individuals already suffering from opioid use disorder will not prevent incident cases. This work will be challenged by a remarkably high degree of complexity involving myriad and highly variable factors along the continuum from initial opioid exposure to long-term opioid use. An organized view of this complex problem should accelerate the pace of innovation and facilitate clinical implementation of research findings. Herein, we propose a theoretical framework and modern nomenclature for characterizing therapeutic opioid exposure and the degree to which it contributes iatrogenically to adverse outcomes. In doing so, we separate the role of exposure from other factors contributing to long-term opioid use, clarify the relationship between opioid exposure and outcomes, emphasize that exposure source is an important consideration for health services research and practice in the areas of pain treatment and opioid prevention, and recommend terminology necessary to quantify therapeutic opioid exposure separately from nonmedical exposure.