An Overview of Opioid-Induced Hyperalgesia and Allodynia

Abnormal pain states paradoxically caused by painkillers

Opioid-induced hyperalgesia (OIH) and allodynia (OIA) are abnormal pain states that result from the class of painkillers called opioids. It's something called a "paradoxical response" in which the drugs you take to relieve pain actually start causing you to be more sensitive to painful stimuli.

A woman holding her prescription medication
Milos Zivkovic / EyeEm / Getty Images

An opioid (sometimes called an opiate or narcotic) is a type of painkiller made from a synthetic form of opium, which is derived from poppies. 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 isn't normally painful, such as a light touch or fabric moving across your skin.

Opioids are only available by prescription. Common opioids include:


OIH and OIA are difficult to spot because the primary symptom is pain—the very thing they're prescribed to treat. What you need to watch for is:

  • Worsening of pain in spite of treatment
  • Pain from abnormal causes, including temperature that's not extreme enough to damage your skin (thermal allodynia), pain from non-abrasive movement across your skin such light rubbing or brushing (mechanical allodynia), or pain from pressure like a gentle hug or a waistband that isn't particularly tight (tactile allodynia)
  • Changes in pain patterns or triggers over time

If the pain you're being treated for doesn't involve allodynia, that's the most likely thing you'll notice. Many people describe is a "skin" pain, similar to a sunburn, and pain from clothing is a common complaint.

Otherwise, the key is to watch for and talk to your healthcare provider about anything new.

Opioid-Induced Pain vs. Increased Drug Tolerance

It's also possible for you to have no idea this is going on and just think your pain management is less effective than it used to be, which is a common problem. Long-term use of opioids is well known for leading 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. Telling the difference isn't easy. Be sure to talk to your healthcare provider 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.

Causes and Risk Factors

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 studies on OIH, some possible mechanisms include:

  • Abnormalities in the way your brain processes pain signals
  • Malfunction of specialized receptors in your brain
  • Increased amounts of the neurotransmitter glutamate, which can over-stimulate your brain cells
  • 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 glutamate and substance P, which transmits nociceptive pain signals

Some of these mechanisms may work together to cause and maintain opioid-induced pain. While much of the research has focused on the central nervous system, the peripheral nervous system may be involved in some cases. The review cited above contains evidence that OIH may develop differently when it comes to different kinds of pain, as well.

Risk Factors

Not everyone who takes opioids will develop OIH or OIA. 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 opioid-induced pain.


OIP is difficult to diagnose. There's no test or scan for it, so your healthcare provider 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 the opioid-induced versions. 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 healthcare provider 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.


When opioids start causing or worsening your pain, you have a few alternatives for changing your pain management strategy.

If the reason for the underlying pain is temporary, then the logical treatment is to go off of opioids. Depending on the dosage and how long you've been taking it, you may need to gradually wean off to avoid additional symptoms.

However, if the cause of pain is ongoing, your healthcare provider may recommend lowering the dosage to see if that gets rid of the opioid-induced pain. When you go off of opioids, it's possible for your OIH or OIA 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, so one may be a problem while others are not.

With opioids, 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 going off of it or lowering your dosage. Your healthcare provider should be able to help you with that.

Sometimes, healthcare providers 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 OIH and possibly OIA.

Other drugs that may be useful in treating opioid-included pain include:

  • Dextromethorphan
  • Methadone (if the OIP isn't in the same class)
  • Buprenorphine
  • Ketamine
  • Dexmedetomidine combined with flurbiprofen axetil

The supplement curcumin (a substance in the spice turmeric) may reverse OIH. In a 2016 study, researchers reported that transplants of a particular type of stem cell reversed OIH as well as morphine tolerance. These treatments need more research before they can be recommended.


Of course, it's better if you can prevent opioid-induced pain in the first place. A 2017 study recommends rotating through classes of opioids, staying on the lowest possible dosage, and combining opioids with non-opioid painkillers. Titrating (building up) to higher doses slowly also may keep OIH and OIA from developing.

Complementary/Alternative Treatments

Part of prevention can including non-drug pain treatments that may help keep your opioid use low while not compromising your quality of life. Some options include:

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

The right non-drug approaches for you depend on the cause of your pain and your overall health. Be sure to discuss these options with your healthcare provider.

A Word From Verywell

Chronic pain takes enough of a toll on your life as it is—you don't need your medications making you hurt worse! At the same time, 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.

4 Sources
Verywell Health uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read our editorial process to learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.
  1. 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.

  2. Hu X, Huang F, Szymusiak M, et al. PLGA-curcumin attenuates opioid-induced hyperalgesia and inhibits spinal CaMKlla. PLoS One. 2016 Jan 8;11(1):e0146393. doi:10.1371/journal.pone.0146393.

  3. Hua Z, Liu L, Shen J, et al. Mesenchymal stem cells reversed morphine tolerance and opioid-induced hyperalgesia. Sci Rep. 2016 Aug 24;6:32096. doi:10.1038/srep32096

  4. Weber L, Yeomans DC, Tzabazis A. Opioid-induced hyperalgesia in clinical anesthesia practice: what has remained from theoretical concepts and experimental studies? Curr Opin Anaesthesiol. 2017 Aug;30(4):458-465. doi:10.1097/ACO.0000000000000485

Additional Reading

By Adrienne Dellwo
Adrienne Dellwo is an experienced journalist who was diagnosed with fibromyalgia and has written extensively on the topic.