What is the likely cause of worsening pain in a girl taking an opioid (opioid) analgesic for pain, such as opioid-induced hyperalgesia (OIh), dependence, or neuroplasticity?

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From the Guidelines

The most likely explanation for the girl's worsening pain despite ongoing opioid use is opioid-induced hyperalgesia (OIh). Opioid-induced hyperalgesia occurs when prolonged use of opioid pain medications paradoxically increases pain sensitivity. In this case, the girl's worsening pain despite ongoing opioid use points to this phenomenon, as supported by the study published in the Annual Review of Medicine in 2018 1.

To address this:

  • Gradually taper and discontinue the current opioid medication under medical supervision.
  • Switch to non-opioid pain management strategies, such as NSAIDs, acetaminophen, or topical treatments.
  • Consider adjunct therapies like physical therapy, cognitive behavioral therapy, or acupuncture. If opioids are still necessary, rotation to a different opioid at a lower equivalent dose may be helpful. For example, if she was on oxycodone, switching to an equivalent dose of morphine or hydromorphone might be considered.

Opioid-induced hyperalgesia occurs due to neuroadaptations in pain-sensing pathways. Prolonged opioid exposure can lead to increased production of excitatory neurotransmitters and enhanced responsiveness of pain receptors, resulting in amplified pain perception, as explained in the study published in the Annals of Internal Medicine in 2006 1. By reducing or changing the opioid therapy, these adaptations can often be reversed, leading to improved pain control. The development of opioid tolerance that necessitates increasing the dose facilitates the emergence of hyperalgesia, making it essential to reassess the opioid treatment plan and consider alternative pain management strategies.

From the Research

Possible Causes of Worsening Pain

  • Opioid-induced hyperalgesia (OIH) is a possible cause of worsening pain in a girl taking an opioid analgesic for pain, as it occurs when opioids paradoxically enhance the pain they are prescribed to ameliorate 2, 3, 4, 5.
  • Dependence on opioids can also lead to worsening pain, as the body adapts to the presence of the opioid and requires increasingly higher doses to achieve the same level of pain relief 5, 6.
  • Neuroplasticity, or changes in the nervous system, can also contribute to worsening pain in individuals taking opioids, as it can lead to sensitization of pronociceptive pathways and decreased reuptake of nociceptive neurotransmitters 5, 6.

Characteristics of Opioid-Induced Hyperalgesia

  • OIH is characterized by a paradoxical response to opioid agonists, resulting in an increased perception of pain rather than an antinociceptive effect 3, 4, 5.
  • The condition can be difficult to diagnose, as it may be confused with other conditions such as tolerance or breakthrough pain 2, 5.
  • OIH can occur in patients taking opioids for acute or chronic pain, and can be triggered by a variety of factors, including high or escalating doses of opioids, or ultra-low doses of opioids 4, 5.

Treatment and Management of Opioid-Induced Hyperalgesia

  • Treatment of OIH typically involves reducing the opioid dosage, tapering off the opioid, or supplementing with NMDA receptor modulators 3, 5.
  • Other pharmacological interventions, such as ketamine, dextromethorphan, and nonsteroidal anti-inflammatory drugs (NSAIDs), may also be effective in managing OIH 3.
  • Non-pharmacological strategies, such as patient education and analgesic management choices, can also play a role in preventing and managing OIH 2, 5.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Pharmacological treatment of opioid-induced hyperalgesia: a review of the evidence.

Journal of pain & palliative care pharmacotherapy, 2011

Research

Mechanisms of opioid-induced tolerance and hyperalgesia.

Pain management nursing : official journal of the American Society of Pain Management Nurses, 2007

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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