Opioid Induced Hyperalgesia: A Counterintuitive Finding of Pain Medicine

By Ted Swing, Ph.D

Medications are one of the most common treatments for pain. Their effectiveness for immediate pain is well-established and they can be effective for treating chronic pain as well. One of the most widely used types of pain medications are opioids, such as morphine or oxycodone. Studies have found that these medications can be effective in treating chronic pain, with an average pain relief of about 30%. Their side effects and risks require close medical supervision to use these medications safely. In addition to the more widely recognized dangers such as increased risk of accidents, addiction and even death, these medications can have a less widely recognized side effect: opioid induced hyperalgesia.

Opioid induced hyperalgesia

The primary effect of opioids is to stimulate specific brain receptors that alleviate pain. This is why these medications have long been used for treating pain. However, doctors and researchers have found that, in some cases, opioids actually have the opposite effect — that is, taking opioids increases the pain that a person feels. Sensations, such as being stuck by a needle, that normally cause mild pain may instead cause extreme pain. The patient may begin to experience new pain or sensitivity in different parts of the body. In some cases the severity of their previous chronic pain conditions also increases. This phenomenon, where taking opioids causes increased sensitivity to pain, is known as opioid induced hyperalgesia (OIH). OIH is well demonstrated in animal studies. Numerous studies have found that mice and rats experience greater sensitivity to pain for several hours after the effects of an opioid have worn off. Some studies in humans also find that higher doses of opioids during a surgery are associated with greater post-operative pain after those opioids have worn off.

It also appears that OIH can occur while a person is still taking opioids. Though the incidence of OIH is unknown, many doctors believe it is more common than was previously realized. OIH may be especially likely for those taking high doses taken for a long time. One study followed 23 patients experiencing severe pain (8/10 on average) despite taking very high doses of opioids. These patients were weaned off their opioids over the course of weeks. The researchers found that these patients’ pain decreased to an average of about 3/10 after stopping their opioids, with 21 of the 23 patients experiencing reduced pain.

Why does opioid induced hyperalgesia occur?

Opioid induced hyperalgesia occurs as a result of changes in the brain and spinal nerves as the body adapts to the effects of opioids. Several neural systems that normally regulate the perception of pain may become overactive in response to the pain relieving effects of opioids, which block normal pain perception. The overactivity of these neural systems can block out or even exceed the pain relieving effect of the drug. This increased pain can last as long as the opioid dose is maintained.

What can be done for opioid induced hyperalgesia?

Only your provider can determine if you have opioid induced hyperalgesia, as several other conditions may have similar symptoms. In many cases when a patient is experiencing OIH, reducing or even eliminating opioids can produce a substantial reduction in pain. In other cases, switching to a different opioid may be effective in reversing OIH and restoring pain relief.

When used responsibly under proper supervision, opioids can be an effective treatment for many types of chronic pain. It is critical to take opioids and other medications as directed by their prescriber. However, in addition to the well known risks, patients and health care providers must be alert to the possibility of opioid induced hyperalgesia. If a low or moderate dose of opioid therapy is producing partial relief of pain, this may represent the full potential benefit of the opioid therapy. Increasing the dose to a high level may not only fail to increase pain relief but in some cases can actually lead to more pain.

Ted Swing has more than 11 years of research experience in psychology and pain medicine and four years of teaching experience, has published in top psychology and medical journals, and has presented his research at major conferences. He received his Ph.D. in Social Psychology from Iowa State University and has been the Research Director at Arizona Pain since May 2012.