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Endogenous Opioid Inhibition of Chronic Low-Back Pain Influences Degree of Back Pain Relief After Morphine Administration
  1. Stephen Bruehl, PhD*,
  2. John W. Burns, PhD,
  3. Rajnish Gupta, MD*,
  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: Stephen Bruehl, PhD, Vanderbilt University Medical Center 701 Medical Arts Bldg, 1211 21st Ave South, Nashville, TN 37212 (e-mail: Stephen.Bruehl{at}


Background and Objectives Factors underlying differential responsiveness to opioid analgesic medications used in chronic pain management are poorly understood. We tested whether individual differences in endogenous opioid inhibition of chronic low-back pain were associated with the magnitude of acute reductions in back pain ratings after morphine administration.

Methods In randomized counterbalanced order over three sessions, 50 chronic low-back pain patients received intravenous naloxone (8 mg), morphine (0.08 mg/kg), or placebo. Back pain intensity was rated predrug and again after peak drug activity was achieved using the McGill Pain Questionnaire–Short Form (Sensory and Affective subscales, VAS Intensity measure). Opioid blockade effect measures to index degree of endogenous opioid inhibition of back pain intensity were derived as the difference between predrug to postdrug changes in pain intensity across placebo and naloxone conditions, with similar morphine responsiveness measures derived across placebo and morphine conditions.

Results Morphine significantly reduced back pain compared with placebo (McGill Pain Questionnaire–Short Form Sensory, VAS; P < 0.01). There were no overall effects of opioid blockade on back pain intensity. However, individual differences in opioid blockade effects were significantly associated with the degree of acute morphine-related reductions in back pain on all measures, even after controlling for effects of age, sex, and chronic pain duration (P < 0.03). Individuals exhibiting greater endogenous opioid inhibition of chronic back pain intensity reported less acute relief of back pain with morphine.

Conclusions Morphine appears to provide better acute relief of chronic back pain in individuals with lower natural opioidergic inhibition of chronic pain intensity. Possible implications for personalized medicine are discussed.

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  • The authors declare no conflict of interest.

    This research was 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.