When clinicians have ruled out an opioid tolerance and suspect opioid-induced hyperalgesia, an initial strategy should be to reduce the opioid dose.
Patients who experience opioid-induced hyperalgesia may benefit from transitioning to methadone for treatment of pain. Opioid-induced hyperalgesia is the result of a neuroplastic change in pain perception that augments pain sensitivity.
Hyperalgesia is described as an enhanced pain response to a noxious stimulus, and opioid induced hyperalgesia occurs after prolonged administration of opioids. It is found more frequently in patients receiving high as opposed to low doses of opioids. Strategies to treat and prevent opioid tolerance and opioid-induced hyperalgesia include using adjuvant drugs for pain treatment (such as anticonvulsants and antidepressants), physical therapy, and opioid rotation.
Opioid rotation is a widely used therapeutic technique in which the type of opioid or route of administration is changed to reduce the side effects and improve its analgesic efficacy. The evidence supporting opioid rotation as a means of improving pain control, however, is lacking.
The use of buprenorphine (a partial mu-opioid receptor agonist but also a kappa-receptor antagonist) and methadone (a mu-opioid receptor agonist and NMDA receptor antagonist) when coadministered with ketamine (an NMDA receptor antagonist) has been associated with less hyperalgesia.
Source: What Special Considerations Should Guide the Safe Use of Methadone? Laura P. Gelfman, Emily J. Chai, in Evidence-Based Practice in Palliative Medicine, 2013