Complications of long-term opioid therapy for management of chronic pain: the paradox of opioid-induced hyperalgesia

J Med Toxicol. 2012 Dec;8(4):387-92. doi: 10.1007/s13181-012-0260-0.


While opioids remain a valid and effective analgesic strategy for patients suffering from a wide variety of painful conditions, they are not a panacea. Increasingly, physicians must balance patient expectations of adequate pain control with known limitations of opioid pharmaceuticals including adverse effects, tolerance, addiction, withdrawal, and drug diversion. Further complicating the issue over the last decade is a growing body of evidence suggesting chronic opioid use may unexpectedly worsen the perception of pain in some individuals. This syndrome, termed opioid-induced hyperalgesia (OIH), fundamentally changes our understanding of opioid pharmacodynamics and may influence our approach to management of chronic pain. This manuscript describes the concept OIH and provides an overview of basic science and clinical research to date attempting to characterize this syndrome, as well as ascertain its clinical relevance. The potential existence of OIH in humans is framed within the context of our current understanding of opioids and our prescribing patterns so that physicians may begin to incorporate these ideas into their philosophy of pain management as further information develops. Animal studies reliably validate OIH in controlled models. Rigorous research protocols in humans are lacking, and we cannot yet confidently conclude that OIH manifests in clinically significant ways. However, clinicians should consider the possibility of OIH when evaluating outcomes of patients on chronic opioid therapy.

Publication types

  • Review

MeSH terms

  • Analgesics, Opioid / administration & dosage
  • Analgesics, Opioid / adverse effects*
  • Analgesics, Opioid / therapeutic use*
  • Animals
  • Chronic Pain / drug therapy*
  • Disease Management
  • Disease Models, Animal
  • Drug Interactions
  • Drug Tolerance
  • Humans
  • Hyperalgesia / chemically induced
  • Hyperalgesia / drug therapy*
  • Nociceptive Pain / drug therapy
  • Randomized Controlled Trials as Topic


  • Analgesics, Opioid