For the past two decades, opioid painkillers have been the doctor-recommended solution for treating acute and chronic pain. But a mounting body of evidence is suggesting that opioid medications like OxyContin and Vicodin may NOT in fact be the best pain management options. In fact, opiate drugs may paradoxically contribute to worsened pain.

Hyperalgesia – When Your Pain Pills Cause MORE Pain

“When we overwhelm the system with large doses of opioids — does the system fight back? We have to accept that there are limitations to any biological system, and if you exceed them, then bad things will happen. And one of those things may be opioid-induced hyperalgesia.”

~ Dr. Martin Angst, anesthesiologist, Stanford University

The proper medical term for this type of pain is “Opioid-Induced Hyperalgesia”.

The idea that opioid pain medications can make some patients more sensitive to pain isn’t exactly new. Way back in 1870, a British doctor was moved to ask the question, “Does morphia tend to encourage the very pain it pretends to relieve?”

Since that time, other physicians have wondered the same thing. In 1880, a German physician remarked how opioids could produce “opposite effects” – including hyperalgesia.

This abnormal sensitivity often develops the opioid dosage has been escalated too rapidly. For example, a 2015 study discovered that surgical patients who were given high doses of opioids suffer worse pain than those patients who received low doses or a placebo.

Although the precise mechanism by which OIH develops isn’t completely understood, it appears the person’s pain threshold is reduced, resulting in increased sensitivity to pain.

Animal Studies Hints How OIH Might Work in Humans

In 2016, researchers at the University of Colorado Boulder performed experiments on lab rats in order to examine the interaction between a nerve injury and opioids. Of special relevance, the effect on nerve pain was still evident even months after the opioid treatment was discontinued.

In the experiment, lab rats were given injuries to simulate chronic nerve pain in humans, such as might be felt from diabetic nerve damage, stroke, or traumatic nerve injury. After the injury, half of the rats were treated with morphine for five days, while the other half group received no opioids.

A third group of rats, the control group, received no injury.

Over the next three months, the rats’ sensitivity to pain was repeatedly tested. After six weeks, the injured rats that were not given morphine had returned to the same level of pain sensitivity as those in the uninjured control group.

However, the rats given morphine for pain took 12 weeks to return to normal, even after the injury appeared to have healed. Significantly, when the control rats were given morphine, their pain threshold likewise dropped, although they returned to normal in just a week.

The implication is that opioid drugs trigger immune signals within the spinal cord that increase pain instead of reducing it – even after the drug is no longer present.

How Is a Diagnosis of Opioid-Induced Hyperalgesia Made?

Although there currently no “official” criteria for an OIH diagnosis, some suggestions have been made:

• The increase in pain can NOT be explained by a worsening or progression of the original presenting condition.
• The increase in pain coincides with a concurrent increase the use of opioid painkillers.
• The possibility of opioid tolerance or withdrawal– both separate conditions from OIH – should be ruled out. While increasing the opioid dosage will overcome tolerance and relieve symptoms of withdrawal, it increases pain sensitivity in OIH sufferers.

How Is Opioid-Induced Hyperalgesia Treated?

Treating OIH is a challenging, time-consuming process. It often involves a degree of trial-and-error to determine which approach is best for the individual patient.

The safest, most-preferred option is simply to completely wean the patient off of ALL opioids. Not only does this treat the pain-causing OIH, it also addresses any co-presenting tolerance and withdrawal.

There are obstacles to this approach, however.

A patient who has been prescribed an opioid medication to manage their pain may not at first understand why that medication is being reduced and will be eventually stopped altogether. It is very important, then, for the doctor to fully explain why the weaning is necessary.

But even when patient understands and cooperates, the process can be a slow and prolonged affair, as the opiate dosage is very gradually tapered. Even if this is done gradually, the patient may experience withdrawal symptoms or incidents of pain caused by the original underlying condition.

Reducing the pain caused by OIH while at the same time effectively managing the pain caused by the underlying condition is one of the biggest challenges to treatment.

For this reason, a person receiving treatment for OIH may need psychotherapy for support.

Benefits to Opioid Weaning

“Today, pain specialists rarely prescribe opioids for chronic pain, unless it’s cancer-related. Reality caught up with us. Over the years, we learn that dependence on opioids develops quickly.”

~ Dr. Richard Rosenquist, M.D., Chairman, Cleveland clinic’s Department of Pain Management

Opioid medications are highly-habit-forming and pose a significant risk for dependence, misuse, addiction, and overdose. Currently, there are approximately 2.6 million Americans who are addicted to opioids. In 2016, there were an estimated 43,000 opioid-related overdose deaths.

Opioid tolerance – the need for higher dosages to achieve the same effect – can develop as little as two weeks.

The most-recent guidelines state that opioids should not be given for chronic non-malignant pain. And even when they are given for short-term acute pain, they should always be dispensed at the lowest dosage and for the shortest duration possible, with frequent follow-ups.

This is the chief advantage to opioid tapering – it manages the patient’s pain while eventually getting them off of the potentially-dangerous medication. Even without the presence of OIH, this is a positive.

Medications for OIH

Sometimes, dose tapering can be supported – or even temporarily replaced by – by rotating different opioid medications. Various classes of opiate medications are tolerated differently, and by rotating these, pain is treated, the progression of tolerance is slowed, and overall opiate consumption is lessened.

Some of the medications that show promise include:

• Methadone – Although OIH can significantly improve when treated with methadone, there is a major caveat. An opioid addict who is currently in a methadone maintenance program may experience worsened OIH.
• Dextromethorphan, particularly when combined with morphine, has demonstrated significant pain relief for the treatment of OIH.
• Buprenorphine, either alone or in combination with naloxone, has shown effectiveness as an anti-hyperalgesia treatment.
• Non-opioid analgesic agents such as pregabalin, ketamine, and propofol may also help with OIH because they activate different areas of the pain pathway.

If Opioid Painkillers ARE Discontinued Due To OIH, How Can Pain Be Managed?

“The fact that opioids did worse is pretty astounding. It calls into question our beliefs about the benefits of opioids.”

~ Dr. Robert Chou, M.D., Professor of Medicine, Oregon Health and Science University

Although the general public and the medical community have been led to believe that opioid drugs are the most effective way to treat chronic pain, a brand-new study by the Minneapolis Veterans Affairs Healthcare System strongly indicates that might not be the case.

This study is one of the first long-term comparison of the effectiveness of opioid drugs such as oxycodone and hydrocodone versus that of over-the-counter remedies.

The results showed that among patients in chronic back pain, opioid medications demonstrated no improvement over OTC medicines, in terms of pain relating to daily functioning, even after an entire year of treatment.  Significantly, opioids were even found to be slightly INFERIOR at controlling the intensity of pain.

Opioid patients also reported far more side effects – constipation, drowsiness, tolerance, etc.

All of the patients participating in the study suffered with arthritis pain in their knee or hip, or chronic back pain. They were treated either with OTC anti-inflammatory medicines like naproxen, with analgesics such as lidocaine, or with opioid painkillers like morphine or oxycodone.

• Among both groups, 60% enjoyed significantly improvement in their daily functioning.
• In the group that received opioids, 41% reported less-intense pain.

• However, in the non-opioid group, 54% said they felt lessened pain intensity
• Patients receiving opioids also reported experiencing twice the number of side effects.

These findings run counter to the way pain has been treated over the last couple of decades and may lead to revised prescribing guidelines.

Finally, other types of adjunct pain treatments help reduce the need for pain-causing opioids.

• Acetaminophen
• Other OTC NSAIDS
• Muscle relaxants
• Antidepressants
• Anticonvulsants

The Limitations of OIH Research

These findings about the possibility of increased pain sensitivity should not be a reason in and of itself to withhold opioid pain medications from people in need. Each person experiences pain differently and because OIH is so poorly understood, it isn’t exactly clear why the condition presents in some patients who receive opioids but not others.

More studies and human trials are needed, and in the meantime, the search for both new pain-relieving solutions and treatments for OIH goes on.