Abstract
Background
Clinical Features of Opioid Hyperalgesia
History
Increasing sensitivity to pain stimuli (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, such as stroking skin with cotton (allodynia).
Presence of other opioid hyperexcitability effects: myoclonus, delirium, or seizures (see Fast Facts #57 and #58).
Proposed Mechanisms
Toxic effect of opioid metabolites (e.g., morphine-3-glucuronide or hydromorphone-3-glucronide).
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).
Add an infusion of a non-opioid NMDA receptor antagonist such as ketamine (see Fast Fact #132).
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.