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Related Experiment Video

Updated: May 14, 2026

Assessment of Morphine-induced Hyperalgesia and Analgesic Tolerance in Mice Using Thermal and Mechanical Nociceptive Modalities

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Published on: July 29, 2014

Tramadol induced paradoxical hyperalgesia.

Seong Heon Lee¹, Soo Young Cho, Hyung Gon Lee

¹Department of Anesthesiology and Pain Medicine, Chonnam National University Medical School, South Korea.

|January 24, 2013

Summary

Opioid-induced hyperalgesia (OIH) is a dangerous side effect where patients become more sensitive to pain. This study highlights OIH in patients taking tramadol, emphasizing the need for recognition and alternative treatments.

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Area of Science:

Pain Management
Pharmacology
Neurology

Background:

Opioids are primary analgesics for various pain types, but concerns include dependence and addiction.
Opioid-induced hyperalgesia (OIH), a paradoxical increase in pain sensitivity, is an often-overlooked complication.
OIH can worsen patient suffering and complicate pain treatment.

Observation:

Three types of OIH exist: withdrawal/maintenance, high/escalating doses, and ultra-low doses.
Most research focuses on the first two OIH types, primarily with morphine.
The third OIH type (ultra-low dose) has been observed in animals but not documented in humans until now.

Findings:

This study presents two human cases of OIH caused by tramadol, an opioid with lower mu-opioid receptor affinity.
These cases occurred in patients with chronic pain during dose titration, presenting with generalized pain despite no disease exacerbation.
This suggests OIH can occur even with ultra-low opioid doses, challenging previous assumptions.

Implications:

Recognizing OIH in tramadol-treated patients is crucial when analgesic effects diminish or unexplained pain arises.
The findings underscore the importance of considering OIH in clinical practice, even with seemingly low-dose opioid therapy.
Switching to alternative analgesics may be necessary if OIH is suspected.