Pain-related effects of trait anger expression: neural substrates and the role of endogenous opioid mechanisms

Abstract

Literature is reviewed indicating that greater tendency to manage anger via direct verbal or physical expression (trait anger-out) is associated with increased acute and chronic pain responsiveness. Neuroimaging data are overviewed supporting overlapping neural circuits underlying regulation of both pain and anger, consisting of brain regions including the rostral anterior cingulate cortex, orbitofrontal cortex, anterior insula, amygdala, and periaqueductal gray. These circuits provide a potential neural basis for observed positive associations between anger-out and pain responsiveness. The role of endogenous opioids in modulating activity in these interlinked brain regions is explored, and implications for understanding pain-related effects of anger-out are described. An opioid dysfunction hypothesis is presented in which inadequate endogenous opioid inhibitory activity in these brain regions contributes to links between trait anger-out and pain. A series of studies is presented that supports the opioid dysfunction hypothesis, further suggesting that gender and genetic factors may moderate these effects. Finally, possible implications of interactions between trait anger-out and state behavioral anger expression on endogenous opioid analgesic activity are described.

Figure 1

Scatterplot of thermal pain threshold (circles) and activation beta weights for ACC area 24 (triangles) as a function of anger-out score. Solid and broken best fit lines are for pain threshold and ACC activation, respectively.

Figure 2

Effects of trait anger-out on opioid blockade effects derived from acute finger pressure (FP) and forearm ischemic task (ISC) visual analog scale (VAS) pain intensity ratings. Blockade effects (y-axis) represent naloxone condition pain ratings minus placebo condition pain ratings. Larger positive blockade effects indicate greater opioid analgesia. Raw VAS ratings used to derive blockade effects potentially ranged from 0−100mm.

Figure 3

Scatterplot of anger-out scores and residualized changes in plasma beta-endorphin (BE, in ng/ml) in response to acute pain stimulation. Positive BE change values indicate greater release of BE in response to acute pain stimuli. BE changes are residualized for pre-pain baseline (i.e., baseline corrected change) and differences across assay plates.

Figure 4

Effects of anger-out on pain threshold opioid blockade effects in male and female participants. Anger-out values plotted are hypothetical values representing one standard deviation (SD) below and above the sample mean. Pain threshold blockade effects (y-axis) reflect placebo condition pain threshold values minus naloxone condition pain threshold values. Larger blockade effects indicate greater opioid analgesia.

Figure 5

Blockade effects on emotional reactivity (anger) to acute pain stimulation by anger-out score. Anger-out values plotted are hypothetical values representing one standard deviation (SD) below and above the sample mean. Anger blockade effects (y-axis) reflect naloxone condition changes in anger from baseline to post-pain minus the comparable placebo condition anger reactivity values. Larger positive blockade effects indicate greater endogenous opioid modulation of anger reactivity. CLBP = Chronic Low Back Pain.

Figure 6

Effects of anger-out on analgesic use (mg of morphine equivalents) in subjects with wild-type versus A118G variant allele of the mu opioid receptor gene.