
Opioid-induced hyperalgesia (OIH) is defined by an increased sensitivity to pain due to long-term exposure to painkillers.[1] This can happen to patients who are taking prescription opioids for the purpose of managing chronic pain. It can also happen to people who take large amounts of painkillers to manage an opioid use disorder (OUD).
For people in recovery from OUD who are also living with chronic pain, it can be especially difficult to avoid relapse when pain levels are high. Even though painkillers will not work as well as they once did, many find that they experience intense cravings for opioids.
If OIH is an issue during recovery, it is essential for patients to work together with their healthcare provider to try different strategies to manage pain safely and effectively without using addictive substances.
Opioid-induced hyperalgesia occurs when chronic exposure to opioids changes how the excitatory and inhibitory pathways communicate within the central nervous system.[2]
There are a number of different theories about how the specific mechanisms of OIH work, or how it occurs in the body. However, most researchers agree that overexposure causes increased activity in pain pathways and decreased activity in the inhibitory pathways when opioids bind to the mu opioid receptors and trigger an increase in glutamate release.[2]
Essentially, when someone takes opioids for too long, receptor desensitization and altered release of neurotransmitters that disrupt the release of endorphins (the “feel-good” chemicals in the brain) create the paradox of experiencing more pain instead of less.
The primary symptom of OIH is an increase in the experience of pain without a new injury or other identifiable source.[3] This could show up in different ways for different people, including these:
It is not always easy for a medical professional to diagnose opioid-induced hyperalgesia because there is no specific test for the disorder. A differential diagnosis is required. A doctor must rule out other possibilities, and if no other issue is determined to be the cause of the pain, a diagnosis of OIH may be given.[4]
In most cases, a physician will need the following to make an OIH diagnosis:
Additionally, a doctor may choose to taper the patient off opioids to see if the pain sensitivity increases or otherwise change the treatment plan in order to see the results.
Each person’s experience with chronic pain, OUD and other co-occurring ailments that impact pain response is different. Therefore, every treatment plan for opioid-induced hyperalgesia will be unique.
In most cases, the treatment plan for OIH will involve a multifaceted approach that includes holistic pain management, a change to non-opioid painkillers, Medication for Addiction Treatment (MAT) and physical therapy or surgery as appropriate.[5]
Here are some of the potential treatments:
When the problem is medication, the first line of defense is often to change the medication regimen. In some cases, this may mean analgesic rotation. In others, it may require tapering and/ or a reduction in dose to test the body’s response.
Analgesic rotation is the act of changing up the prescribed opioid in the hopes of mitigating OIH. For example, if the person is taking oxycodone, the doctor may change to hydrocodone to see if the increased pain sensitization decreases. In some cases, this switch is enough to alter the mu-opioid receptor binding process and stop the up-regulation of pain pathways and the down-regulation of inhibitory pathways.
If switching up opioid medications is not effective, the doctor may choose to taper the person off all opioids slowly. This involves gradually reducing the dose as they make the switch to non-opioid pain medications.[6]
This process should be attempted without medical supervision. A structured tapering plan is required in order to minimize withdrawal symptoms, but the plan may need to be altered if there are complications. Only a doctor will know when that needs to happen and how best to address any challenges safely.
In addition to non-opioid painkillers, there are a number of holistic interventions that can be helpful in moderating the experience of pain, especially when used in combination with each other.
Physical therapy is one of the first lines of defense against chronic pain that is caused by accident or injury. When OIH is part of the puzzle, physical therapy has been proven to be an effective part of a comprehensive treatment plan.[5] The exercises and stretching involved can improve mobility and lessen the amount of discomfort experienced by the patient.
Cognitive behavioral therapy (CBT) is a talk therapy tool that is commonly used in addiction treatment and recovery. It can have a positive impact on healing from a variety of medical disorders, including opioid-induced hyperalgesia.
Though CBT does not address pain directly, it can help with the perception of pain, increase motivation to engage in alternative therapies like physical therapy, and improve mood. Especially when the person is living with a mood disorder like anxiety or depression, CBT can be especially effective in helping the individual to decrease their experience of pain.[7]
There are a number of complementary treatments that also may be effective in the treatment of chronic pain when they are included in a comprehensive treatment plan. Options such as acupuncture, yoga or mindfulness meditation can all help to improve mood and decrease the perception of pain. In the case of yoga, it may help to improve mobility and decrease tightness in muscles.
It is important to note that alternative therapies alone are not an appropriate treatment for chronic pain, substance misuse or opioid-induced hyperalgesia. It is essential to work with a healthcare provider to determine which alternative therapies will be most appropriate in order to avoid potential harm.
MAT is often the first line of defense against OUD. In cases where opioid-induced hyperalgesia is triggered by long-term opioid misuse during the course of OUD, MAT that helps the patient stop using all opioid medications can be the best course of care.
Just like with all treatments for OIH, MAT should only be undertaken with the support of a medical professional. Medications like Suboxone are prescribed on a specific schedule according to the patient’s needs.
If you believe that MAT may be the right course of action for you or someone you love with OUD and opioid-induced hyperalgesia, reach out for more information today. At Bicycle Health, we offer Suboxone via our telehealth MAT services.
The best treatment for opioid-induced hyperalgesia involves a combination of medication management, non-opioid pain management strategies and, in some cases, MAT. The specific combination of therapies, the type and dose of medication, and the use of alternative treatment options should be chosen based on the individual patient’s medical history and current needs.

Peter Manza, PhD received his BA in Psychology and Biology from the University of Rochester and his PhD in Integrative Neuroscience at Stony Brook University. He is currently working as a research scientist in Washington, DC. His research focuses on the role of the brain dopamine system in substance use disorders and in aging. He also studies brain function in obesity and eating disorders.
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