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Opioid-Induced Hyperalgesia: Causes, Symptoms, Treatment

Reviewed by Dr. Kamemba

  • December 9, 2024

Reviewed by Dr. Tulman

  • December 9, 2024

Opioid-induced hyperalgesia is a condition characterized by heightened sensitivity to pain as a result of opioid use. Although opioid medications are prescribed for pain management, they can paradoxically increase pain sensitivity, especially when taken for a prolonged period or in high doses.

Anyone taking these medications should learn more about opioid-induced hyperalgesia, as it can happen unexpectedly, and it is easy to mistake it for opioid tolerance.

This article will explain the key things you should know about this condition, including how to spot it, treat it, and differentiate it from opioid tolerance.

What Is Opioid-Induced Hyperalgesia, and How Does It Occur?

Opioid-induced hyperalgesia (OIH) is a condition in which exposure to opioids increases the patient’s sensitivity to pain instead of decreasing it.

Opioids are a broad class of potent medications typically prescribed for moderate-to-severe pain. Some examples of common opioid analgesics include:

  • Fentanyl
  • Morphine
  • Tapentadol
  • Oxycodone
  • Hydrocodone

Although opioid pain medications are highly effective in controlling pain, their efficacy diminishes with prolonged use as patients develop opioid tolerance. Paradoxically, opioid therapy, especially at high doses or over a prolonged time, can make the pain worse in some patients.

While opioid-tolerant patients typically experience better pain relief with increased doses, this diminishes over time and opioid-induced hyperalgesia. In fact, increasing the dosage may further aggravate the pain or cause it to spread to other areas.

What Is Opioid-Induced Hyperalgesia, and How Does It Occur?

Opioid-induced hyperalgesia can increase the patient’s sensitivity to either the pain they initially sought treatment for or other types of pain. For example, someone who takes opioids for chronic pain management may become more sensitive to minor external stimuli, such as light pressure, or find their pain spreading toward other areas.

How exactly opioid-induced hyperalgesia occurs isn’t fully understood yet. According to researchers from the University of Pennsylvania, some mechanisms that may possibly be involved in its development include the central glutaminergic system and the descending pain pathways.

Opioids relieve pain by preventing the transmission of pain signals between the body and the brain. However, they may also damage certain parts of the CNS, leading to increased pain sensitivity rather than relief.

In most cases, opioid-induced hyperalgesia occurs with prolonged opioid use, especially at high doses. Given that this also increases the risk of opioid dependence, addiction, and overdose, it is in your best interest to take opioids for a minimum time at the lowest effective dose.

Signs and Symptoms of Opioid-Induced Hyperalgesia

The main signs and symptoms of opioid-induced hyperalgesia are decreased opioid effectiveness and increasing sensitivity to pain that persists even with increased opioid use.

People with OIH suffer from growing pain, and increased doses further exacerbate it rather than providing relief. Their pain becomes more intense, even if the health condition that led them to take opioids in the first place isn’t getting any worse.

Other possible signs and symptoms of opioid-induced hyperalgesia include:

  • Allodynia. Opioid-induced hyperalgesia can sometimes manifest as opioid-induced allodynia, which is a type of pain that is caused by typically non-painful stimuli. For example, light pressure on the skin, such as clothes brushing against it, may cause pain in people with this symptom.
  • Widespread pain. Opioid-induced hyperalgesia could cause the pain to spread beyond the original site. If you’re taking opioids for back pain, for example, you may start to experience pain in your limbs, or your pain might spread to a larger area of the body.
  • Changes in pain quality. Patients with opioid-induced hyperalgesia often find that their pain changes in quality, e.g., dull pain becomes sharp, throbbing pain turns to burning pain, and so forth. A study by Grisell Vargas-Schaffer et al. found that this is the second most frequent symptom of OIH after the worsening of pain despite increased opioid doses. 32% of patients with opioid-induced hyperalgesia experience changes in the quality of pain.  

Next, let’s explore the connection between opioid-induced hyperalgesia and opioid addiction, also known as opioid use disorder (OUD).

The Connection Between Opioid Use Disorder and Opioid-Induced Hyperalgesia

The connection between opioid use disorder and opioid-induced hyperalgesia is complex, as OIH can both facilitate the development of OUD and complicate its treatment. Likewise, OUD can lead to opioid-induced hyperalgesia and lead to challenges in its treatment.

Opioid use disorder is a treatable condition marked by the inability to control opioid use. It typically follows untreated opioid dependence, which anyone taking opioids risks developing since these drugs gradually alter brain chemistry. Opioid abuse, i.e., taking opioids in other ways than prescribed, can also increase the risk of opioid dependence and addiction.

Man holding a bunch of meds in his right hand

People with opioid-induced hyperalgesia may be at a higher risk of developing OUD. Escalating pain can lead to higher opioid doses, which can paradoxically exacerbate pain and increase the risk of addiction.

Similarly, suffering from OUD can make you more likely to develop opioid-induced hyperalgesia. OIH usually stems from repeated opioid exposure and high opioid doses, both of which are common in people addicted to opioids.

Co-occurring OUD and OIH can be very difficult to treat. Opioid-induced hyperalgesia treatment typically entails a reduction in opioid dosage, which can trigger uncomfortable withdrawal symptoms, including cravings, in people with OUD. Even when opioid use causes pain or other harm, OUD can make opioid cessation and reduction virtually impossible.

Many people struggling with OUD opt for medication-assisted treatment (MAT), which involves a combination of opioid-replacement medications, such as methadone, in addition to counseling and other therapies. However, since these medications are opioids, they can also cause or exacerbate opioid-induced hyperalgesia, making OUD treatment and recovery even more challenging.

Traditional Methods for Treating Opioid-Induced Hyperalgesia

Traditional methods for treating opioid-induced hyperalgesia include opioid dose reduction, opioid rotation, and administering non-opioid medications.

Let’s explore these opioid-induced hyperalgesia treatment methods in more detail:

  • Opioid rotation. Although all opioids act on opioid receptors, they may affect different pathways. Therefore, opioid-induced hyperalgesia may improve in some people once they switch to another type of opioid. Many patients rotate to methadone, as it has weak N-methyl-D-aspartate (NMDA) receptor antagonist effects, which may help alleviate OIH. In some patients, however, it can exacerbate pain. Not to mention, all opioids have a high potential for abuse, dependence, and addiction.
  • Dose reduction. While increased doses worsen pain in patients with opioid-induced hyperalgesia, reduced doses may improve OIH. However, dose reductions can trigger uncomfortable opioid withdrawal symptoms in patients with co-occurring opioid dependence and OIH, making treatment more challenging.
  • Non-opioid drugs. Non-opioid medications, such as non-steroidal anti-inflammatory drugs (NSAIDs) or NMDA receptor antagonists like ketamine, may be used as part of opioid-induced hyperalgesia treatment. These are usually combined with an opioid dose reduction.

Ultimately, the most effective way to treat opioid-induced hyperalgesia is to get off opioids, as they are the culprits behind this condition.

However, for those struggling with opioid dependence, this is easier said than done. Seeking professional treatment for opioid dependence is vital because it reduces the risk of severe withdrawal symptoms, complications, and relapse.

Importantly, not all opioid addiction treatments are equally safe and effective. Addressing the neurobiological causes of opioid dependence is paramount to achieving lasting recovery. Yet, traditional treatments like MAT or anesthesia-assisted rapid detox don’t even acknowledge the underlying causes of opioid dependence. As a result, they often lead to relapse.

How ANR Opioid Dependence Treatment Targets OIH

Innovative treatment that eradicates opioid dependence

Developed by Dr. Andre Waismann, Accelerated Neuro-Regulation (ANR) is an innovative treatment that eradicates opioid dependence by reversing opioid-induced changes to the brain. Unlike traditional therapies, ANR is the first and only treatment that addresses the root of the problem instead of managing its symptoms.

Here are some key advantages of ANR treatment:

#1. Long-Lasting Recovery

ANR treatment facilitates lasting recovery by tackling the root cause of opioid dependence—the chemical imbalance resulting from prolonged opioid use. ANR re-regulates the endorphin-receptor system, returning the brain to a pre-dependence state. As a result, it eliminates withdrawal symptoms, negating the risk of relapse.

Furthermore, ANR enables you to swiftly get off opioids, even if you’ve been taking them for years. By restoring normal brain function, this treatment helps eliminate opioids from the system, go back to a healthy life, and recover from opioid-induced hyperalgesia.

After the treatment, you won’t have to take potentially addictive and OIH-inducing opioid-replacement drugs. Rather than substituting one opioid with another, ANR allows you to return to an opioid-free life. As of today, this revolutionary treatment has supported nearly 25,000 people worldwide in achieving a lasting recovery from opioid dependence.

#2. Personalized Approach

While other treatments take a one-size-fits-all approach to opioid dependence treatment, ANR offers a personalized approach. Each patient receives a treatment plan tailored to their unique medical history and needs. Therefore, ANR is suitable for virtually everyone, including those with co-occurring health conditions, be they liver disease or opioid-induced hyperalgesia.

#3. Patient Safety

Designed according to the highest patient safety and care standards, ANR is scientifically proven to be very safe and highly effective. The procedure is performed in an ICU setting of fully accredited hospitals equipped with ultra-modern medical equipment.

Furthermore, the ANR team comprises highly experienced and compassionate healthcare professionals, including anesthesiologists, critical care physicians, and more.

Reclaim Your Life With the Groundbreaking ANR Treatment

If you’re dependent on opioids, know it’s not your fault—anyone taking these drugs can fall victim to them. Whether you’ve been battling opioid dependence for weeks, months, or decades, ANR can help you break the cycle of opioid abuse and reclaim the life you deserve.

With ANR, you won’t have to spend weeks in a rehabilitation facility or continue taking MAT medications for years. By modulating the endorphin-receptor system and reversing the damage opioids cause to the brain, ANR can help you make a lasting recovery from opioid dependence within a matter of days. The average hospital stay for our patients lasts only 36 hours.

Ready to leave opioids behind? Get started with ANR today by contacting us for a free, fully confidential consultation!

Key Takeaways

The bottom line is that opioid-induced hyperalgesia is one of the adverse effects that may occur due to opioid use. The only way to prevent it is not to take opioids in the first place. If you must take opioids, it’s best to limit it to the shortest duration and the smallest amount possible to reduce the risk of OIH.

Before you leave, here’s a summary of the key points we covered today:

  • Opioid-induced hyperalgesia happens when opioids increase pain sensitivity instead of decreasing it.
  • Some signs and symptoms of opioid-induced hyperalgesia include decreased opioid effectiveness, growing pain despite escalating opioid doses, high sensitivity to normally non-painful external stimuli, and pain spreading beyond the original site.
  • Co-occurring opioid use disorder and opioid-induced hyperalgesia can present challenges in the treatment of both conditions.
  • While getting off opioids is a surefire way to overcome opioid-induced hyperalgesia, OIH may also be treated with opioid rotation, decreased opioid doses, and non-opioid medications.
  • ANR can help you break free from opioid dependence within a matter of days, thereby allowing you to recover from opioid-induced hyperalgesia.

Opioid-Induced Hyperalgesia FAQ

#1. Is opioid-induced hyperalgesia the same as opioid tolerance?

Opioid-induced hyperalgesia is not the same as opioid tolerance. Although both lower the effectiveness of opioids, they respond differently to dosage increases. While opioid-tolerant people experience improved pain relief with higher doses, dosage increases often escalate pain in people with opioid-induced hyperalgesia.

#2. Can opioid-induced hyperalgesia be treated?

Opioid-induced hyperalgesia can be treated. The treatment for opioid-induced hyperalgesia typically involves a reduction in opioid dose, opioid rotation (switching from one opioid to another), and using alternative pain management techniques, such as non-opioid pain medications. N-methyl-D-aspartate (NMDA) receptor antagonists may also be used to treat OIH.

#3. How common is opioid-induced hyperalgesia?

It is not easy to tell how common opioid-induced hyperalgesia is because it remains largely underresearched. However, researchers from the Massachusetts General Hospital Center for Translational Pain Research found that 55% of primary care physicians had treated at least one patient with opioid-induced hyperalgesia. Therefore, it may not be rare.

Additional Information

Speedballing: Risk & Effects of Mixing Opioids and Stimulants

How to Taper off Opioids?

Opioid Toxicity

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Dr. Andre Waismann

Dr. Waismann identified the biological roots of opioid dependency, Since then he has successfully treated more than 25,000 patients worldwide that are struggling with opioid addiction.


Throughout his career, he has lectured and educated health professionals in dozens of countries around the world to this day.

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