Opioids are the drugs that are most commonly used for the treatment of chronic pain. Unfortunately, maladaptive responses to opioids (tolerance, dependence and OIH (opioid-induced hyperalgesia)) have greatly limited their clinical utility [1, 2]. As examples, the gradual loss of analgesic effect, worsening pain despite dosage increases, and greatly exaggerated postoperative pain have all been attributed to OIH [3–5]. Despite decades of study, we have no specific therapies that can limit or overcome the problems associated with chronic opioid use. The lack of new approaches results from our limited understanding of the mechanisms mediating the maladaptive responses.
