Opioid-Induced Hyperalgesia
addiction treatment

Patients with chronic pain being treated with opioids can commonly be expected to develop tolerances to the drug with longer-term pain management treatment, but the emergence of certain, uniquely sensitive pain characteristics can be red flags for a potential differential diagnosis of hyperalgesia.


“Hyperalgesia is not easy to diagnose,” said Dr. Silverman, who is medical director of Coastal Pain Medicine in Pompano Beach, Florida.

“When a chronic pain patient isn’t getting better, a clinician asks: is the patient developing a tolerance and needs more opioid or does he have opioid-induced hyperalgesia?”

In the United States there is an epidemic of chronic pain that parallels the ever- increasing utilization of opioids. This increase in opioid use has led to misuse and abuse and has left in its wake thousands of fatalities. Yearly, there are greater than 15,000 deaths. Although the general consensus is that opioids can be prescribed safely and effectively with prudent risk mitigation strategies, certain side effects/complications can be difficult to treat.

Addiction, abuse, and diversion are usually the focus of such efforts, and become relatively straightforward when investigated. However, other side effects to opioid therapycan be somewhat difficult to assess and even more so to treat. Opioid-induced hyperalgesia (OIH), related to but different from tolerance, is one such complication of opioid therapy. There is preclinical and clinical evidence for such, as well as the clinical implications for the pain practitioner.

Sanford M. Silverman, MD, Pain Week Journal, 02/2014

Key Symptoms

Key symptoms offer important clues, Dr. Silverman said. Patients with opioid-induced hyperalgesia will develop an increased sensitization to pain that may be unlike their original pain.

“The first thing to understand is this is a diffuse, spreading kind of pain,” he said. “Patients develop an acute insensitivity to pain even though they may be stable and functioning on their opiates.”

The distinction from the development of a tolerance should be clear. “This is not just a lack of efficacy of the pain management — that’s tolerance, and everybody develops a tolerance to almost every exogenous thing. It’s a defense mechanism your body engages in and is not hyperalgesia.”

A classic case of hyperalgesia will be a patient who initially presented with postlaminectomy syndrome with back and leg pain and has been receiving opioid therapy for years.

“Now you start noticing something different — the patient’s pain diagram is spreading, and now he also has headaches, neck pain, arm pain.”

“That’s opioid-induced hyperalgesia,” Dr. Silverman said. “Not only is the back and leg pain worse, but now the fire has spread and kind of gone out of control.”

A stabilization of symptoms when opioids are increased should be a tip-off that the patient has in fact developed a tolerance to the drugs, and the response should help to disprove a diagnosis of hyperalgesia.

Conversely, with hyperalgesia, there may also be an initial response, but the relief is typically fleeting.

“If an increase in opiates results in only temporary relief or a worsening of symptoms, that’s opioid-induced hyperalgesia,” Dr. Silverman said. “They will get better for a while, but then they only get worse. Their normal pain will not only increase, but it will spread and become multimodal.”

Importantly, clinicians should rule out other factors, including the progression of a disease, such as cancer, or a new injury causing new pain.

Additionally, hyperalgesia should not be mistaken for allodynia. Whereas hyperalgesia is characterized as a painful response to painful stimuli, allodynia involves oversensitized, increased pain in response to even non-painful stimuli, such as just brushing against the skin.