Trait anger expressiveness and pain-induced beta-endorphin release: Support for the opioid dysfunction hypothesis

Abstract

The anger management styles of anger-in (inhibition) and anger-out (direct expression) are positively associated with pain responsiveness. Opioid blockade studies suggest that hyperalgesic effects of trait anger-out, but not those of trait anger-in, are mediated in part by opioid analgesic system dysfunction. The current study tested the opioid dysfunction hypothesis of anger-out using an alternative index of opioid function: pain-induced changes in plasma endogenous opioids. Plasma beta-endorphin (BE) was assessed at rest and again following exposure to three laboratory acute pain tasks (finger pressure, ischemic, and thermal) in 14 healthy controls and 13 chronic low back pain (LBP) subjects. As expected, acute pain ratings correlated positively with measures of anger-in (both groups) and anger-out (LBP group; p's<.05). Greater pain-induced increases in BE were associated with significantly lower pain ratings in both groups (p's <.05). Hierarchical multiple regression indicated that greater anger-out significantly predicted smaller pain-induced BE increases (p<.05). Subject type did not moderate this association (p>.10). Anger-in did not display significant main or interaction effects on pain-induced BE changes (p's >.10). The significant association between angerout and BE release partially mediated the hyperalgesic effects of anger-out on pain unpleasantness, and was not attenuated by statistical control of general negative affect. This suggests unique associations with expressive anger regulation. Elevated trait anger-out therefore appears to be associated with opioid analgesic system dysfunction, whether it is indexed by responses to opioid blockade or by examining circulating endogenous opioid levels. Possible "state × trait" interactions on these anger-related opioid system differences are discussed.

The mu opioid receptor A118G gene polymorphism moderates effects of trait anger-out on acute pain sensitivity

“…Using Figure 3 as an example, it appears that high anger-outs, whom prior work suggests have inadequate endogenous opioid analgesia [7,9,10], do in fact display effective endogenous analgesia (presumably opioid-mediated) if they possess the variant 118G allele. Such speculation is consistent with work indicating that the variant allele is associated with greater beta-endorphin receptor binding [5], increased Ca 2+ channel inhibition for a given level of opioid agonist activation [33], and diminished acute pain responsiveness [20,32].…”

“…Primary analyses tested for moderation by the A118G SNP of the relationship between anger management style measures and acute pain responses. Given previous work suggesting opioid-related effects and genetic moderation effects for anger-out but not anger-in [6,7,[9][10][11], it was expected that any genetic moderation effects would be limited to the anger-out variable.…”

“…Prior work suggests that anger-out, but not angerin, may impact on pain via endogenous opioid mechanisms [6,7,9,10]. Moreover, a growing literature indicates the A118G SNP of the mu opioid receptor gene affects opioid receptor function and pain responses [5,20,28,[30][31][32][33]44].…”

“…The last measure includes separate subscales assessing trait anger-in (tendency to manage anger via inhibition of expression) and anger-out (tendency to manage anger through direct verbal or physical expression). This anger-out scale has demonstrated previous associations with measures of opioid function [6,7,9,10]. The BDI, STAI, and TRANG were included to evaluate whether hypothesized effects were due to anger management style per se, or rather, might be better accounted for by overlap with general negative affect.…”

“…Results of studies using multiple acute pain stimuli (finger pressure, ischemic, thermal, noxious electrical stimulation) and various measures of opioid function (opioid blockade with naloxone and naltrexone, pain-induced plasma beta-endorphin release) all point towards an association between elevated trait anger-out and diminished endogenous opioid analgesia [6,7,9,10]. For example, opioid blockade with naloxone increased self-reported pain intensity in those scoring low on a measure of anger-out but not those high on anger-out, suggesting functional endogenous opioid analgesia in the former but not the latter [7].…”