Is Opioid-Induced Hyperalgesia a Real Phenomenon?

“Is opioid-induced hyperalgesia a real phenomenon?” asked Jeffrey Gudin, MD, “Yes, I think there is something there,” he answered at the beginning of his education session during the 2014 American Academy of Pain Management annual clinical meeting in Phoenix, AZ.

Gudin, Director of Pain Management, Englewood Hospital and Medical Center, Englewood, NJ, described opioid-induced hyperalgesia (OIH) as dramatically increased sensitivity to painful stimuli or pain elicited by nonpainful stimulus following treatment with opioids. Patients typically report pain that is different from the initial complaint, but not always. It is most commonly seen in patients receiving high doses — 100 mg and above of the morphine equivalent. Patients with OIH may also show other signs of toxicity, for example, myoclonus, delirium, and seizures (indicating neuroexcitability). In addition, increasing opioid doses in patients exhibiting OIH will make the pain worse, and pain can be improved by removing or eliminated the opioid.

OIH is “a state of nociceptive sensitization caused by a paradoxical response upon exposure to specific or certain amounts of opioids,” said Gudin. He also explained that according to the top theories in the literature “the underlying mechanisms are not fully understood, but an imbalance of pronociceptive and antinociceptive processes seem to be involved.”

Gudin described some of the individual case reports and small studies that provide evidence for OIH, but also said the evidence is conflicting. A number of studies have reported increased sensitivity to cold pressor, electrical, and pressure pain in opioid addicts maintained on methadone. Increased sensitivity to cold pressor pain has been the most consistently observed indication of OIH, with some methadone-maintained patients unable to tolerate very cold water for any amount of time (normal tolerance would be a few minutes). Postoperative opioid exposure came under scrutiny about 10 years ago when two well-designed studies showed increased pain in postoperative patients even with increased doses of opioids, but these studies have not been repeatable. OIH has been better established in chronic pain patients, but treatment options are so limited that opioids must be used. “OIH is not a reason to avoid opioids,” Gudin emphasized, “but, there is enough evidence to keep it in mind.”

The treatment options for OIH include “reducing, rotating, or completely tapering the opioid — the simplest way to test for OIH,” Gudin explained. When rotating opioids, doses calculated from reference conversion charts should be reduced by 50% or even more. Clear data indicates that switching from an opioid to methadone reduced OIH, although OIH is also seen in methadone-maintained patients. Drugs that diminish neuroexcitability, such as antiepileptics, antidepressants, and NMDA antagonists (for example ketamine) may also reduce OIH. Gudin proposes using these options before an insult, such as surgery, that will require opioids, thus calming the nervous system.

In summary, Gudin explained that OIH should not limit the use of opioids, but practitioners should be on the lookout for unusual pain patterns, especially pain that cannot be explained or pain that is diffuse and non-specific.