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Opioid Painkillers Sometimes Make Pain Worse, According to Evidence Review

As new evidence becomes available, healthcare providers are becoming increasingly aware that ongoing opioid therapy for chronic pain might actually worsen the pain in some patients a condition called Opioid-Induced Hyperalgesia or OIH.

Opioid Painkillers Sometimes Make Pain Worse, According to Evidence Review
Chicago, IL, August 20, 2008 --( Opioid medications are essential for helping to relieve all types of serious pain. However, relatively recent evidence suggests that in some patients they can paradoxically worsen the pain.

“Actually, this possible negative effect of opioids, such as morphine, to cause increased sensitivity to pain was observed in the 19th Century,” says Peggy Compton, RN, PhD. “Today, we call this opioid-induced hyperalgesia, or OIH.”

Compton is an Associate Professor of Nursing at the UCLA School of Nursing, Los Angeles, and a well-known researcher and author in the pain management field. Her extensive review of the clinical evidence on OIH, exclusively for Pain Treatment Topics and published at the website, is titled “The OIH Paradox: Can Opioids Make Pain Worse?”

The full document can be accessed at:

Fortunately, it seems that OIH does not arise in the majority of patients taking opioid analgesics, but when it does occur it can be difficult to manage. In addition to OIH, pain increasing during opioid therapy can indicate several other conditions that must be considered, including: 1) worsening pain-causing disease, 2) tolerance to opioid effects, 3) opioid withdrawal symptoms, or 4) pseudoaddiction (opioid-seeking due to unrelieved pain). For these conditions, increasing the opioid dose usually helps relieve pain.

A patient who is addicted to opioids may complain of worsening pain but may not be helped by increasing the opioid dose. In fact, signs of addiction may emerge further, such as difficulty controlling opioid use, a preoccupation with obtaining opioids, or other misbehavior.

In the case of OIH, increasing the opioid dose will actually make the pain worse. Often, the pain is difficult for the patient to describe and can spread beyond the original point of pain. According to Compton’s review, several strategies may help prevent OIH or to deal with OIH if it occurs:

>> The opioid dose should be kept as low as is clinically effective for managing pain.

>> Additional medications can be used to help minimize the need for opioids, such as COX-2 inhibitors, dextromethorphan, and others.

>> Long-acting opioids are preferred over shorter-acting formulations for chronic pain.

>> If a particular opioid becomes ineffective, it is often helpful to rotate to a completely different opioid drug (methadone is especially useful for opioid rotation).

>> New research suggests combining low-doses of opioid antagonists (eg, naltrexone) with opioid therapy to counteract development of OIH.

Compton observes that there are still many unanswered questions about OIH, and research investigations are ongoing. Meanwhile, it is essential for healthcare providers to carefully monitor patients’ responses to opioid therapy and recognize that several opioid-related responses other than OIH can lessen opioid-analgesic effectiveness. In some cases, higher dosing is needed; however, if OIH occurs, other strategies should be employed to provide patients the pain relief they need and deserve.


Pain Treatment Topics and the associated website provide open and free access to noncommercial, evidence-based clinical news, information, research, and education on the causes and effective treatment of the many types of pain conditions. It is independently produced and currently supported by an unrestricted educational grant from Covidien/Mallinckrodt Inc., St. Louis, MO, a leading manufacturer of generic opioid analgesic products.

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Pain Treatment Topics
Stewart B. Leavitt, MA, PhD

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