Personality Trait Predictors of Placebo Analgesia and Neurobiological Correlates

Abstract

Personality traits have been shown to interact with environmental cues to modulate biological responses including treatment responses, and potentially having a role in the formation of placebo effects. Here, we assessed psychological traits in 50 healthy controls as to their capacity to predict placebo analgesic effects, placebo-induced activation of m-opioid neurotransmission and changes in cortisol plasma levels during a sustained experimental pain challenge (hypertonic saline infused in the masseter muscle) with and without placebo administration. Statistical analyses showed that an aggregate of scores from Ego-Resiliency, NEO Altruism, NEO Straightforwardness (positive predictors) and NEO Angry Hostility (negative predictor) scales accounted for 25% of the variance in placebo analgesic responses. Molecular imaging showed that subjects scoring above the median in a composite of those trait measures also presented greater placebo-induced activation of m-opioid neurotransmission in the subgenual and dorsal anterior cingulate cortex (ACC), orbitofrontal cortex, insula, nucleus accumbens, amygdala and periaqueductal gray (PAG). Endogenous opioid release in the dorsal ACC and PAG was positively correlated with placebo-induced reductions in pain ratings. Significant reductions in cortisol levels were observed during placebo administration and were positively correlated with decreases in pain ratings, m-opioid system activation in the dorsal ACC and PAG, and as a trend, negatively with NEO Angry Hostility scores. Our results show that personality traits explain a substantial proportion of the variance in placebo analgesic responses and are further associated with activations in endogenous opioid neurotransmission, and as a trend cortisol plasma levels. This initial data, if replicated in larger sample, suggest that simple trait measures easily deployable in the field could be utilized to reduce variability in clinical trials, but may also point to measures of individual resiliency in the face of aversive stimuli such as persistent pain and potentially other stressors.

Neuro-Bio-Behavioral Mechanisms of Placebo and Nocebo Responses: Implications for Clinical Trials and Clinical Practice

“…In a recent fMRI study on placebo analgesia, the administration of the D 2/3 antagonist haloperidol blocked placebo-related activity in the striatum but had no effect on analgesia or on activity in brain regions believed to Neuro-Bio-Behavioral Mechanisms of Placebo and Nocebo Responses encode pain intensity (Wrobel et al, 2014). Taken together, although these data suggest endogenous dopaminergic pathways somehow contributing to the individual placebo analgesic response, the distinct role of the dopaminergic system in placebo analgesia requires further investigation (Peciña et al, 2013a).…”

“…These PET studies have substantiated that the placebo-related activity and connectivity changes within cingulofrontal and subcortical networks including the PAG observed with fMRI involve m-opioidergic neurotransmission (for review, see . The contribution of opioidergic neurotransmission is further substantiated by pharmacological fMRI studies, i.e., by showing that naloxone blocks placebo-related activity in the PAG and rostral ventromedial medulla and PAG-rACC connectivity along with impaired behavioral analgesia (Eippert et al, 2009a), as well as in seminal studies linking variability in genes modulating opioidergic mechanisms with an individual's placebo analgesic response (Hall et al, 2012;Peciña et al, 2013aPeciña et al, ,b, 2014.…”

“…Recent evidence supports the putative relevance of several psychosocial variables for an individual's placebo responsiveness. These include anxiety and fear Lyby et al, 2011), hypnotic suggestibility (De Pascalis et al, 2002), locus of control and self-efficacy (Horing et al, 2015), hostility (Peciña et al, 2013a), coping abilities (Schneider et al, 2006), dispositional optimism (Morton et al, 2009;Geers et al, 2010), and empathy for socially induced placebo analgesia Hunter et al, 2014). However, no consistent personality profile has emerged so far across different clinical conditions (Horing et al, 2014).…”

Placebo improves pleasure and pain through opposite modulation of sensory processing

“…In clinical settings, placebo responses can confound assumptions about the physical or "true" effects of the treatment, but can also be used to optimize a treatment (44)(45)(46). Although the amount of expectancy, desirability (47), personality traits (48), and biomarkers, like gray matter density of the NAc (25), sometimes correlate with placebo responses, it has been notoriously difficult to predict placebo responses across different contexts (49,50). Most placebo research has addressed the effect of a treatment on one clinical outcome in isolation (e.g., reduction of pain).…”

Associations Of Positive Personality Characteristics With Psychophysiological Response To Stressors: Literature Review

“…However, it is not clear how positive personal characteristics affect not only cognitive coping (stress coping strategies) but physiological reaction to stress (stressors) as well. For example optimism does not relate with better response to pain (Pecina et al, 2013) and physical stressor (cold water), but predicts better response to social stressor (public speaking) (Terrill, Ruiz, & Garofalo, 2010). Some findings indicate that the interaction of high optimism and high discrimination predicts worse response to stressors as compared with only high discrimination (Richman, Bennett, Pek, Siegler, & Williams, 2007) which in fact suggests that optimism may not always have a positive impact upon one's health.…”