Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
, 4 (3), 123-30

Opioid-induced Hyperalgesia: Pathophysiology and Clinical Implications


Opioid-induced Hyperalgesia: Pathophysiology and Clinical Implications

Sukanya Mitra. J Opioid Manag.


Background: Opioid-induced hyperalgesia (OIH) refers to a phenomenon whereby opioid administration results in a lowering of pain threshold, clinically manifest as apparent opioid tolerance, worsening pain despite accelerating opioid doses, and abnormal pain symptoms such as allodynia.

Aim: The current review, while providing a clinically oriented updated overview on the pathophysiology of OIH, focuses predominantly on evidence-based clinical and management aspects of this important and often baffling phenomenon.

Method: Online and manual search using key words such as opioid-induced hyperalgesia, opioid-induced abnormal pain sensitivity, opioid hyperalgesia, opioid-induced paradoxical pain, or opioid-induced abnormal pain, followed by full-text access and further crossreferencing.

Results: The underlying pathophysiology of this phenomenon, although still unclear, appears to be related to an opioid-induced imbalance between the internal antinociceptive and pronociceptive systems. Clinical differentiation of an apparent opioid tolerance state includes OIH. Once diagnosed or provisionally considered, treatment strategies could include opioid dose reduction, opioid rotation, use of agents with NMDA receptor antagonism, and a properly timed coxib.

Conclusion: Despite initial skepticism and reservations, the phenomenon of OIH in humans is now accepted a clinical reality and a challenge faced by anesthesiologists, intensivists, pain specialists, and other workers in a diverse range of settings from perioperative care to palliative care medicine.

Similar articles

  • Opioid Induced Hyperalgesia: Clinical Implications for the Pain Practitioner
    SM Silverman. Pain Physician 12 (3), 679-84. PMID 19461836. - Review
    Opioids have been and continue to be used for the treatment of chronic pain. Evidence supports the notion that opioids can be safely administered in patients with chronic …
  • A Comprehensive Review of Opioid-Induced Hyperalgesia
    M Lee et al. Pain Physician 14 (2), 145-61. PMID 21412369. - Review
    Opioid-induced hyperalgesia (OIH) is defined as a state of nociceptive sensitization caused by exposure to opioids. The condition is characterized by a paradoxical respon …
  • Dexmedetomidine Infusion for the Management of Opioid-Induced Hyperalgesia
    M Belgrade et al. Pain Med 11 (12), 1819-26. PMID 21040434. - Case Reports
    The cases presented provide support for the clinical utility of alpha-2 agonists during opioid dose reduction in patients with OIH as well suggesting that they may contri …
  • Opioid Induced Hyperalgesia
    P Yi et al. Pain Med 16 Suppl 1, S32-6. PMID 26461074. - Review
    As more opioids are prescribed, especially to treat chronic nonmalignant pain, OIH becomes more of a relevant and significant issue. Although the exact mechanisms of OIH …
  • [The Clinical Relevance of Opioid-Induced Hyperalgesia Remains Unresolved]
    J Sørensen et al. Ugeskr Laeger 173 (13), 965-8. PMID 21453637.
    Opioids are widely used as analgesics in chronic pain of malignant as well as non-malignant origin. During opioid treatment, pain is occasionally worsened. This could be …
See all similar articles

Cited by 15 PubMed Central articles

See all "Cited by" articles

MeSH terms