Nociceptive Flexion Reflex Threshold is No Suitable Marker for Diagnosing Opioid-Induced Hyperalgesia

Abstract

Background

Opioid induced hyperalgesia (OIH) describes a state of altered pain sensation due to opioid exposure. It often occurs among persons with opioid use disorder receiving substitution therapy.

Methods

The purpose of this study was to find out, whether OIH diagnosis could be facilitated by an objective pain indicating marker: the Nociceptive Flexion Reflex (NFR). Forty persons with opioid use disorder, 20 of them maintained on methadone and 20 treated with buprenorphine, as well as a control group of 20 opioid-free subjects, were examined. It was aimed to find out whether and in which way these opioid agonists alter reflex threshold (NFR-T). A cold-pressor test was performed to investigate the prevalence of OIH. Furthermore, electrical stimulation and electromyography analyzation were used for NFR-T measurement. Subjective pain ratings were evaluated with a numeric rating scale.

Results

Significantly increased sensitivity to cold pressor pain was found in both maintenance groups when compared to their opioid-free counterparts (p < 0.001). Neither methadone nor buprenorphine showed any effect on NFR-T. This might be explained by the reflex approaching at the wrong location in the central nervous system. Consequently, NFR-T is not a suitable marker for diagnosing OIH.

Conclusion

Although methadone and buprenorphine have been proven to cause OIH, no effect on NFR-T was observed. A statistically significant effect could have been observed with a larger number of participants. Further research, with special focus on patients’ adjuvant medication, should be conducted in the future, to facilitate diagnosis of OIH and provide appropriate pain management for maintenance patients.

Keywords:

• hyperalgesia
• analgesics
• opioid
• substance-related disorders
• methadone
• buprenorphine

Acknowledgment

The authors would like to thank N. Lenuweit, who helped with recruiting probands.

Author Contributions

All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; took part in drafting, revising or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work.

Disclosure

All authors report no conflicts of interest in this work.