Opioid-Induced Hyperalgesia (OIH): An Emerging Treatment Challenge

Pain is the most common reason for which people seek medical attention.

Generally opioids are prescribed for the management of pain. However, chronic pain can persist or worsen despite aggressive opioid therapy. This condition is called opioid-induced hyperalgesia (OIH).

OIH is defined as increased nociceptive sensitization caused by exposure to opioids.

Diagnosis -

• Pain resolves once the treatment with the opioid is discontinued. The pain relief from opioid discontinuation in OIH is a gradual process.

• The pain is diffuse in nature, of lesser quality and difficult to pinpoint.

• Pain can persist even after the removal of the original source of pain or healing of the damaged tissue.

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• Despite rest and undertaking other measures which would relieve pain, the pain in OIH worsens as the treatment progresses.

Differential diagnosis -

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• Opioid tolerance- There is reduced analgesic response to the opioid dose in both, opiod tolerance and OIH. They likely share many of the same cellular mechanisms. But tolerance can be overcome by increasing the opioid dose, whereas pain worsens if the opioid dose is increased in a person with OIH. Tolerance tends to develop slowly over time, whereas the increased pain resulting from opioid treatment occurs relatively quickly.

• Undertreated pain- If opioid dose is suboptimal, then increasing the dose should lead to pain relief. However, in case of OIH the pain worsens with increase in dose.

Etiology -

Activation of the NMDA receptor- Certain opioids and their metabolites agonize the N-methyl-D-aspartate (NMDA) receptor. Activation of the NMDA receptor causes an influx of calcium that enhances the excitability of the neuron due to which the painful impulses initiated by circulating substance P or other noxious stimuli are transmitted more readily.

Several animal and human studies have revealed that a patient with OIH experiences pain relief on administration of NMDA receptor antagonists.

Treatment -

• The best strategy is total discontinuation of the problematic opioid. Reduce the dose gradually to minimize adverse withdrawal effects. Hyperalgesia might worsen early in the discontinuation process. But discontinuation is of little use to the patient who requires opioid-type pain relief.

• If pain persists and some amount of analgesia with opioids is required, patients may obtain relief by reducing the opioid dose. Several patients find an acceptable balance of analgesia and relief from hyperalgesia upon opioid dose reduction. Methadone is an opioid which can be used for treating pain in the patient with OIH. Buprenorphine might have some potential for treating the pain in OIH. However, its clinical utility is yet to be explained fully.

• Switching from one class of opioids to another can be helpful.

• Supplementing opioid therapy with a cyclo-oxygenase-2 (COX-2) inhibitor can be helpful. Considering the role of NMDA receptor in OIH, antagonizing this receptor can be a reasonable treatment strategy. Though ketamine is effective in reversing hyperalgesia, its adverse side-effects like tachyarrhythmia, hypertension, cognitive impairments, and psychomimetic reactions, including mood changes, vivid dreams, delirium, hallucinations, and sedation prevent it from being a viable treatment option. Dextromethorphan is another NMDA receptor antagonist. Tramadol and meperidine have some NMDA receptor antagonist activity.

Reference: Opioid-Induced Hyperalgesia: An Emerging Treatment Challenge; Shelby Bottemiller; US Pharmacist 2012

Source-Medindia