Fast Fact and Concept #142: OPIOID-INDUCED HYPERALGESIA

Author: Winifred G. Teuteberg, MD

Opioid-induced hyperalgesia is a clinical phenomenon is characterized by increasing in pain in patients who are receiving increasing doses of opioids. This Fast Fact reviews the clinical findings and treatment options

Clinical features of opioid hyperalgesia

History

• Increasing sensitivity to pain stimulus (hyperalgesia)
• Worsening pain despite increasing doses of opioids
• Pain that becomes more diffuse, extending beyond the distribution of pre-existing pain
• Can occur at any dose of opioid, but more commonly with high parenteral doses of morphine or hydromorphone and/or in the setting of renal failure.

Physical Examination

• Pain elicited from ordinarily non-painful stimuli, e.g. stroking skin with cotton (Allodynia)
• Presence of other opioid hyperexcitability effects: myoclonus, delirium or seizures (See Fast Facts #57,58)

Proposed mechanisms

• Toxic effect of opioid metabolites (morphine-3-glucuronide (M3G) or hydromorphone-3-glucronide (H3G)
• Central sensitization as a result of opioid-related activation of N-methyl-D-asparate (NMDA) receptors in the central nervous system
• Increase in spinal dynorphin activity
• Enhanced descending facilitation from the rostral ventromedial medulla
• Activation of intracellular protein kinase C

Therapies

• Reduce or discontinue the current opioid
• Change opioid to one with less risk of neurotoxic effects: fentanyl or methadone. (See Fast Fact #75: Methadone for Pain)
• Add an infusion of a non-narcotic NMDA receptor antagonist such as ketamine. (See Fast Fact #132: Ketamine use in Palliative Care)
• Add a non-opioid adjuvant such as acetaminophen or an NSAID
• Initiate epidural, intrathecal, regional or local anesthesia and taper/discontinue systemic opioids.
• Increase hydration if clinically appropriate.

Conclusion

Opioids can lead to a paradoxical increase in pain. Opioid-induced hyperalgesia should be considered in any patient with increasing pain that is not responding to increasing opioids. Referral to pain/palliative care professionals is appropriate to help develop a management strategy.

References

1. Mao J. Opioid-induced abnormal pain sensitivity: implications in clinical opioid therapy. Pain 2000; 100 213-217.
2. Portenoy RK, Forbes K, Lussier D, Hanks G (2004). Difficult pain problems: an integrated approach. In Oxford Textbook of Palliative Medicine 3 rd ed (ed. Doyle D, Hanks G, Cherny N, Calman K), p. 439. Oxford: Oxford University Press.
3. Laird D, Lovel T. Paradoxical pain (letter). Lancet 1993; 341: 241.
4. Walker SM, Cousins MJ. Reduction in hyperalgesia and intrathecal morphine requirements by low-dose ketamine infusion (letter). J Pain Symptom Manage 1997; 14:129-133.
5. Carroll IR, et al. Management of perioperative pain in patients chronically consuming opioids. Reg Anesth Pain Med 2004; 6)576-591.

Copyright/Referencing Information: Users are free to download and distribute Fast Facts for educational purposes only. Citation for referencing: Teuteberg W. Fast Facts and Concepts #142; Opioid-Induced Hyperalgesia. September, 2005. End-of-Life / Palliative Education Resource Center www.eperc.mcw.edu.

Fast Facts were edited by David Weissman MD, Palliative Care Center, Medical College of Wisconsin until January 2007.  For comments/questions write to the current editor, Drew Rosielle MD: drosiell@mcw.edu. The complete set of Fast Facts is available at EPERC: www.eperc.mcw.edu

Disclaimer: Fast Facts provide educational information, this information is not medical advice. Health care providers should exercise their own independent clinical judgment. Some Fast Fact information cites the use of a product in dosage, for an indication, or in a manner other than that recommended in the product labeling. Accordingly, the official prescribing information should be consulted before any such product is used.

Purpose: Self-Study Guide, Teaching

Audience(s)

ACGME Competencies: Medical Knowledge and Patient Care

Keyword(s): Pain>opioids