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 magnitude of acute reductions in back pain ratings following morphine administration. Methods In randomized, counterbalanced order over three sessions, 50 chronic low back pain patients received intravenous naloxone (8mg), morphine (0.08 mg/kg), or placebo. Back pain intensity was rated pre-drug 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 pre-to post-drug 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 to placebo (MPQ-Sensory, VAS; P < .01). There were no overall effects of opioid blockade on back pain intensity. However, individual differences in opioid blockade effects were significantly associated with 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 < .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.

Endogenous Opioid Function and Responses to Morphine: The Moderating Effects of Anger Expressiveness

“…Thus, individuals low in the tendency to express anger may benefit greatly from administration of morphine if their innate capacity to generate endogenous opioid analgesia is also low. The findings we reported 5,6 – that individuals with low endogenous opioid function exhibit high levels of morphine analgesic responses – may pertain most strongly to those low in anger-out. Thus, only individuals low in endogenous opioid function and anger expressiveness may benefit from supplementation of deficient endogenous opioid analgesia by use of exogenous opioid analgesics.…”

“…First, the morphine response for both healthy controls and chronic pain participants who reported both high levels of anger-out and exhibited low endogenous opioid function was smaller than the morphine response for healthy controls and chronic pain participants who reported low high levels of anger-out and exhibited low endogenous opioid function. In previous work, 5,6 we showed that individuals with low endogenous opioid function exhibited high levels of morphine analgesic responses to both induced acute pain and spontaneous low back pain. We surmised that people with poor endogenous opioid function could compensate for their low endogenous analgesic capacity by supplementing deficient endogenous analgesia with exogenous opioids, like morphine.…”

“…Results of our other work suggest that high levels of endogenous opioid function predict relatively low analgesic response to morphine to both acute and chronic pain. 5,6 These latter two reports were based on a study in which healthy controls and individuals with chronic low back pain underwent acute pain induction under three (counterbalanced) conditions: 1) placebo, 2) intravenous naloxone to block endogenous opioids; 3) intravenous morphine. This method gave measures of both endogenous opioid function and opioid analgesic response.…”

“…We found that endogenous opioid function was inversely related to analgesic effects of opioid medication on acute pain stimuli among all participants, and on the intensity of spontaneous low back pain among those with chronic low back pain. 5,6 …”

“…In the present study, we report additional analyses of the parent study described above, 5,6 but with a larger sample of both healthy controls and individuals with chronic low back pain. We integrate our past findings by proposing that the relationships between endogenous opioid function and morphine analgesic response may be moderated by trait anger expressiveness.…”