Breaking the Pain Cycle: Ketamine Therapy for Opioid-Induced Hyperalgesia

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What Are Opioids?

Opioids are a class of medications widely prescribed by physicians to manage chronic or severe pain. They are typically used to treat conditions such as post-operative pain, cancer-related pain, injury-induced pain, and even pain following motor vehicle accidents. Opioids work by binding to opioid receptors located in the brain, spinal cord, and other parts of the body, blocking pain signals and providing relief. Some common opioids include morphine, oxycodone, and hydrocodone.

What Is Opioid-Induced Hyperalgesia (OIH)?

Opioid-induced hyperalgesia (OIH) is a paradoxical condition where opioids, instead of reducing pain, increase a patient’s sensitivity to it. In other words, opioids cause the very thing they are meant to alleviate: more intense, widespread pain. This hypersensitivity typically presents as pain that worsens with higher doses of opioids and may even spread beyond the original site of injury or discomfort.

Symptoms of OIH: 

  • Increased pain sensitivity, often described as sharp or burning, that worsens with opioid usage. 
  • Pain that becomes more generalized and less localized over time. 
  • Lack of pain relief, even with escalating opioid dosages.

Mechanisms Behind OIH:

Although the exact causes of OIH are still being researched, there are two primary theories explaining this phenomenon: 

  • Dysfunction of Descending Pain Pathways: Normally, the body has mechanisms to regulate and suppress pain signals. Prolonged opioid use may disrupt these pathways, leading to an exaggerated pain response and heightened sensitivity. 
  • NMDA Receptor Activation: Opioids may overstimulate the glutaminergic system, leading to the activation of NMDA (N-methyl-D-aspartate) receptors. This heightened activity can amplify pain signals and create a hyperalgesic state, further intensifying the patient’s pain.

Differentiating OIH from Opioid Tolerance:

While opioid tolerance and OIH both involve a diminished response to opioids, they are fundamentally different. Opioid tolerance occurs when higher doses are needed to achieve the same level of pain relief, while OIH results in increased pain as opioid doses rise. Importantly, reducing opioid dosages can help alleviate OIH, whereas tolerance typically requires increasing dosages for effective relief.

What Is Ketamine?

Ketamine is a synthetic compound that has been widely used as an anesthetic in medical practice. It has unique properties, including analgesic, hypnotic, and amnesic effects, which make it useful for pain management, particularly in surgical settings. On a biochemical level, ketamine functions as a noncompetitive antagonist of NMDA receptors, playing a critical role in pain modulation and reducing hyperalgesia.

Ketamine for OIH

Given its mechanism of action, ketamine can be highly effective in treating opioid-induced hyperalgesia. By blocking the NMDA receptors associated with OIH, ketamine can help reset pain pathways, reducing the hypersensitization that opioids create. Additionally, ketamine can help to prevent opioid tolerance, allowing for more effective pain relief at lower opioid dosages.

Studies show that low-dose ketamine infusions may alleviate symptoms of OIH by reducing opioid-induced pain sensitization, enabling patients to regain their baseline pain tolerance. This therapeutic approach not only helps relieve OIH, but also reduces the need for escalating opioid dosages and lowers the risk of long-term dependence.

Why Choose Ketamine for OIH?

Ketamine therapy offers several advantages for patients suffering from opioid-induced hyperalgesia: 

  • Rapid Pain Relief: Ketamine acts quickly, often providing relief within hours or days after treatment. 
  • Reduced Opioid Usage: Ketamine’s ability to desensitize NMDA receptors means that patients can hope to achieve pain relief with lower doses of opioids, helping to break the cycle of escalating dosages. 
  • Non-Invasive Therapy: Ketamine infusions are minimally invasive and can be administered in a clinical setting with minimal recovery time. 
  • Effective for Chronic Pain: Ketamine is especially effective in managing chronic pain syndromes, including those linked to opioid use.

Post-Treatment Considerations

After undergoing ketamine therapy for OIH, patients may experience mild side effects such as drowsiness or dizziness, which generally subside within a few hours. It's essential to follow up with your physician regularly to assess treatment progress and adjust your pain management plan as needed.

At Ospina Medical, Dr. Matthew Kohler specializes in using ketamine therapy for the treatment of OIH and other chronic pain conditions. With his expertise in pain management and personalized care plans, patients can experience long-lasting relief and reduced reliance on opioids.

Seeking Treatment at Ospina Medical

If you or a loved one is struggling with opioid-induced hyperalgesia or chronic pain, ketamine therapy could be the key to regaining your quality of life. Book a consultation with our team today to explore your options and develop a tailored treatment plan that best fits your needs.


Written By: Cherubina Rubannelsonkumar

Edited By: Camden Rowe

Medically Reviewed By: Matthew Kohler, MD

* All information subject to change. Images may contain models. Individual results are not guaranteed and may vary.