Pain is the most common reason for which people seek medical
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
OIH is defined as
increased nociceptive sensitization caused by exposure to opioids.
Pain resolves once the treatment
with the opioid is discontinued. The pain relief from opioid discontinuation in OIH is a gradual
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.
Despite rest and undertaking
other measures which would relieve pain, the pain in OIH worsens as the treatment progresses.
Differential diagnosis -
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
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
Activation of the
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
Several animal and human studies have revealed that a patient with OIH experiences pain relief on
administration of NMDA receptor antagonists.
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
Reference: Opioid-Induced Hyperalgesia: An Emerging
Treatment Challenge; Shelby Bottemiller; US Pharmacist 2012