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Relationship Between Endogenous Opioid Function and Opioid Analgesic Adverse Effects
  1. Rajnish K. Gupta, MD*,
  2. Stephen Bruehl, PhD*,
  3. John W. Burns, PhD,
  4. Asokumar Buvanendran, MD,
  5. Melissa Chont, MLAS*,
  6. Erik Schuster, MA and
  7. Christopher R. France, PhD§
  1. *Department of Anesthesiology, Vanderbilt University School of Medicine, Nashville, TN
  2. Department of Behavioral Science, Rush University, Chicago, IL
  3. Department of Anesthesiology, Rush University, Chicago, IL
  4. §Department of Psychology, Ohio University, Athens, OH
  1. Address correspondence to: Rajnish K. Gupta, MD, Department of Anesthesiology, Vanderbilt University, 1301 Medical Center Dr, 4648 TVC, Nashville, TN 37232–5614 (e-mail: raj.gupta{at}


Background and Objectives Our recent work indicates that endogenous opioid activity influences analgesic responses to opioid medications. This secondary analysis evaluated whether endogenous opioid activity is associated with degree of opioid analgesic adverse effects, and whether chronic pain status and sex affect these adverse effects.

Methods Using a double-blind, randomized, placebo-controlled, crossover design, 51 subjects with chronic low back pain and 38 healthy controls participated in 3 separate sessions, undergoing 2 laboratory-evoked pain tasks (ischemic and thermal) after receiving placebo, naloxone, or morphine. Endogenous opioid system function was indexed by the difference in pain responses between the placebo and naloxone conditions. These measures were examined for associations with morphine-related adverse effects.

Results Chronic pain subjects reported significantly greater itching and unpleasant bodily sensations with morphine than controls (P < 0.05). Across groups, only 6 of 112 possible associations between adverse effects and blockade effects were significant. For the ischemic task, higher endogenous opioid function was associated with greater itching (visual analog scale [VAS]; P < 0.05), numbness (tolerance; P < 0.001), dry mouth (tolerance; P < 0.05), and unpleasant bodily sensations (VAS; P < 0.05). For the thermal task, higher endogenous opioid function was associated with greater numbness (VAS; P < 0.05) and feeling carefree (VAS; P < 0.05). There were no significant main or interaction effects of chronic pain status or sex on these findings.

Conclusions No consistent relationships were observed between endogenous opioid function and morphine-related adverse effects. This is in stark contrast to our previous observation of strong relationships between elevated endogenous opioid function and smaller morphine analgesic effects.

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  • The authors declare no conflict of interest.

    Supported by NIH Grant R01-DA031726 and CTSA award UL1TR000445 from the National Center for Advancing Translational Sciences. Contents of this work are solely the responsibility of the authors and do not necessarily represent official views of the National Center for Advancing Translational Sciences or the National Institutes of Health.

    Presented at the Association of University Anesthesiologists, March 2013.