Endogenous opioid inhibition of chronic low-back pain influences degree of back pain relief after morphine administration

Abstract

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.

Conflict of interest statement

Conflict of Interest:

The authors have no conflicts of interest to report.

Figures

Figure 1

A and B. Scatterplots of associations between standardized opioid blockade effects on chronic low back pain and respective standardized morphine effects for MPQ-Sensory (1A) and VAS Intensity (1B) measures. Positive blockade effects indicate endogenous opioid inhibition of chronic pain intensity and positive morphine effects indicate morphine analgesic effects on chronic pain intensity.

Figure 1

A and B. Scatterplots of associations between standardized opioid blockade effects on chronic low back pain and respective standardized morphine effects for MPQ-Sensory (1A) and VAS Intensity (1B) measures. Positive blockade effects indicate endogenous opioid inhibition of chronic pain intensity and positive morphine effects indicate morphine analgesic effects on chronic pain intensity.

Figure 2

A and B. Boxplots portraying the distribution of standardized opioid blockade effects and standardized morphine effects for MPQ-Sensory (2A) and VAS Intensity (2B) measures. Positive blockade effects indicate endogenous opioid inhibition of chronic pain intensity and positive morphine effects indicate morphine analgesic effects on chronic pain intensity.

Figure 2

A and B. Boxplots portraying the distribution of standardized opioid blockade effects and standardized morphine effects for MPQ-Sensory (2A) and VAS Intensity (2B) measures. Positive blockade effects indicate endogenous opioid inhibition of chronic pain intensity and positive morphine effects indicate morphine analgesic effects on chronic pain intensity.