Opioid-Induced Hyperalgesia & Allodynia

Causes, Diagnosis, & Treatment

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People who live with chronic pain sometimes depend on prescription painkillers to function. However, one of the most common types of painkillers can, with prolonged use, start making your pain worse.

When that happens, it's called opioid-induced hyperalgesia (OIH) or opioid-induced allodynia (OIA). Here's what those phrases mean:

  • An opioid, sometimes called an opiate or narcotic, is a type of painkiller made from a man-made form of opium.
  • Hyperalgesia is amplified pain; processes in the nervous system work to increase the intensity of the pain you feel.
  • Allodynia is pain that's caused by something that shouldn't cause pain, such as a light touch or fabric moving across your skin.

When opioids start causing or worsening your pain, you'll likely need to wean off of them and look for alternative ways to manage your pain levels.

Opioid-induced pain (OIP) can be hard to diagnose, especially in someone with a pain condition that already involves hyperalgesia and/or allodynia.

Opioids are only available by prescription. Some drugs contain only an opioid while others combine the opioid with another drug such as acetaminophen. Common opioids include:

What Causes Opioid-Induced Pain?

Scientists aren't yet sure what causes OIH. OIA was recognized much more recently and we know even less about it than we do OIH.

However, researchers are exploring several possibilities.

According to a review of OIH published in the journal Pain Physician, some possible mechanisms include:

  • Abnormalities in the way your brain processes pain signals
  • Specialized receptors in your brain malfunctioning
  • Increased amounts of the neurotransmitter glutamate, which stimulates your brain cells, sometimes over-stimulating them to the point of death
  • Excess activity of receptors in the spinal cord that stimulate special sensory nerves, called nociceptors, in your peripheral nervous system
  • Decreased reuptake of certain neurotransmitters, which keeps elevated levels active in the brain
  • Heightened sensitivity of spinal neurons to the neurotransmitters substance P (which transmits nociceptive pain signals) and glutamate

Some of these mechanisms may work together to cause and maintain OIP. While much of the research has focused on the central nervous system, the peripheral nervous system may be involved in some cases.

The Pain Physician review cites evidence that OIP may develop differently when it comes to different kinds of pain, as well.

Who's at Risk for Opioid-Induced Pain?

Not everyone who takes opioids will develop OIP. Research suggests that genetics may play a role. Taking opioids regularly for a long time increases your risk, as does taking high doses. Rapidly increasing your dosage also puts you at an elevated risk.

Because many people develop a tolerance to these drugs, it's normal for the amount you take for chronic pain to increase over time, meaning you become more and more likely to develop OIP.

Diagnosing Opioid-Induced Pain

OIP is difficult to diagnose.

There's no test or scan for it, so your doctor has to consider your symptoms and look for other possible causes of increased or new pain. This is called a diagnosis of exclusion, because it can only be made when other possibilities are excluded.

A serious barrier to a diagnosis of OIP is pain conditions that feature what's called "central pain" or "central sensitization." These conditions include fibromyalgia, rheumatoid arthritis, migraine, irritable bowel syndrome, ME/chronic fatigue syndrome, and post-traumatic stress disorder. People with these conditions often already have hyperalgesia and/or allodynia, which can mask OIP.

Regardless of the cause of your pain, the important thing to watch for is a change in the severity or nature of your pain. Look for these types of changes:

  • A more widespread or diffuse pain when the underlying cause is stable or improving
  • Increased pain severity in spite of the underlying cause remaining stable or improving
  • Increased pain after opioid dosage goes up
  • Decreased pain when you take fewer painkillers

The more you're able to tell your doctor about how your pain has changed and how it may relate to your opioid usage, the easier it will be to get a clear picture of what's causing the pain.

OIP vs. Increased Drug Tolerance

Complicating the diagnostic process is increasing drug tolerance. Long-term use of these drugs is well known to lead to an increased tolerance, which can lead to regularly increased dosages.

So sometimes, pain levels go up not because the opioids are causing it, but because you've developed a tolerance to the medication, which means it just isn't working as well as it used to. How do you tell the difference?

It's not easy. Be sure to talk to your doctor about what's going on and how to figure out what's causing your pain. Experimenting with dosage on your own can be extremely dangerous, and it may not give you helpful information.

Treating Opioid-Induced Pain

If the reason for the underlying pain is gone, then the logical treatment is to go off of opioids. Depending on the dosage and how long it's been taken, that may require a gradual weaning process to avoid withdrawal symptoms.

If, however, the cause of pain is ongoing, your doctor may recommend lowering the dosage to see if that gets rid of the OIP. When you go off of opioids, it's possible for your OIP pain to temporarily get worse before going away.

You may also find relief by switching the type of opioid you use. For example, hydrocodone, fentanyl, and tramadol are all from different classes.

Sometimes, doctors will try adding a different type of painkiller—either a COX-2 inhibitor or non-steroidal anti-inflammatory (NSAID)—along with a low dose of opioids. These drugs may help counter the abnormal actions of glutamate and substance P that are believed to contribute to some cases of OIP.

Other drugs that may be useful in treating OIP include:

The supplement curcumin (a substance in the spice turmeric) may reverse OIH, according to a 2016 study in PLoS One.

In a 2016 study published in Scientific Reports, researchers reported that transplants of a particular type of stem cell reversed OIH as well as morphine tolerance.

Preventing Opioid-Induced Pain

Of course, it's better if you can prevent OIP in the first place. A 2017 study published in Current Opinions in Anaesthesiology recommends rotating through classes of opioids, staying on the lowest possible dosage, and combining opioids with non-opioid painkillers. Titrating to higher doses slowly also may keep OIP from developing.

You may also want to explore non-medicinal treatments for your pain to help keep your opioid use low while not compromising quality of life.

Non-Drug Pain Treatments

The right non-drug treatments for you depends on the cause of your pain and is something you should discuss with your doctor. Common pain interventions include:

Some people with chronic pain find relief from gentle exercises such as:

A Word From Verywell

If you notice an increase in pain or a change in the nature of your pain, talk to your doctor about whether it could be due to your opioids. Chronic pain takes enough of a toll on your life as it is—you don't need your medications making you hurt worse!

If you and your doctor decide you should stop taking it, make sure you learn how to wean off of it properly and follow the instructions.

With these drugs, addiction is a possibility. There's no shame in that—it's a natural consequence of the medication. However, it could mean that you need extra help. That's also something to discuss with your doctor.

It can be really scary to stop taking a medication that you've depended on to function. Try to focus on how much it could reduce your pain and improve your life, and remember that you do have alternative treatments to explore.

Sources:

Lee M, Silverman SM, Hanse H, Patel VB, Manchikanti L. A comprehensive review of opioid-induced hyperalgesia. Pain physician. 2011 Mar-Apr;14(2):145-61.

Li SQ, Xing YL, Chen WN, et al. Activation of NMDA receptor is associated with up-regulation of COX-2 expression in the spinal dorsal horn during nociceptive inputs in rats. Neurochem Res. 2009;34:1451-1463. 

Ramasubbu C, Gupta A. Pharmacological treatment of opioid-induced hyperalgesia: a review of the evidence. Journal of pain & palliative care pharmacotherapy. 2011;25(3):219-30. doi: 10.3109/15360288.2011.589490.

Silverman S. Opioid induced hyperalgesia: clinical implications for the pain practitioner. Pain Physician. 2009;12:679-684. 

Wasserman RA, Brummett CM, Goesling J, Tsodikov A, Hassett AL. Characteristics of chornic pain patients who take opioids and persistently report high pain intensity. Regional anesthesia and pain medicine. 2014 Jan-Feb;39(1):13-7. doi: 10.1097/AAP.0000000000000024.

Yu Z, Wu W, Wu X, et al. Protective effects of dexmedetomidine combined with flurbiprofen axetil on remifentanil-induced hyperalgesia: a randomized controlled trial. Experimental and therapeutic medicine. 2016 Oct;12(4):2622-2628.

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