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Updated: May 1, 2026

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Relationship between endogenous opioid function and opioid analgesic adverse effects.

Rajnish K Gupta1, Stephen Bruehl, John W Burns

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Summary

Endogenous opioid activity did not consistently correlate with morphine adverse effects in chronic pain patients or healthy controls. This contrasts with previous findings on opioid analgesic responses.

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Area of Science:

  • Pharmacology
  • Neuroscience
  • Pain Medicine

Background:

  • Endogenous opioid activity influences responses to opioid analgesics.
  • Previous research linked endogenous opioid function to analgesic effects of opioids.
  • This study investigates the link between endogenous opioid activity and adverse effects of opioid analgesics.

Purpose of the Study:

  • To determine if endogenous opioid activity is associated with opioid analgesic adverse effects.
  • To explore if chronic pain status and sex modify these associations.

Main Methods:

  • A double-blind, randomized, placebo-controlled, crossover study.
  • 51 chronic low back pain patients and 38 healthy controls participated.
  • Endogenous opioid function was assessed using placebo and naloxone conditions during pain tasks; morphine-related adverse effects were measured.

Main Results:

  • Chronic pain patients reported more itching and unpleasant sensations with morphine than controls.
  • Few significant associations were found between endogenous opioid function and adverse effects.
  • Some specific adverse effects, like itching and numbness, showed weak correlations with endogenous opioid function during certain pain tasks.

Conclusions:

  • No consistent relationship was observed between endogenous opioid system function and morphine-related adverse effects.
  • This finding contrasts with prior research demonstrating a link between endogenous opioid function and reduced analgesic efficacy of morphine.
  • The role of endogenous opioids in mediating opioid-induced adverse effects requires further investigation.