Abstract
It is generally believed that the placebo response can elicit an analgesic effect, whilst the nocebo response can elicit a hyperalgesia effect in pain. Placebo analgesia and nocebo hyperalgesia effects are increasing concerns for researchers. Growing evidence suggests personality differences have an impact on both placebo and nocebo effects. However, previous studies have not reached a unified conclusion. We designed this study to explore the personality differences of functional magnetic resonance imaging (fMRI) signals in placebo response and nocebo response by using psychophysiological interaction (PPI) analysis. 30 healthy subjects underwent conditioning induction training to establish expectations of placebo effect and nocebo effect, and then, all subjects completed the following experimental procedures: (1) baseline scanning, (2) acute pain model establishment, (3) pain status scanning, and (4) pseudorandom scanning of block design of placebo response or nocebo response. Behavioral data were collected after each scan. The results of this study showed that (1) there were significant differences of VAS placebo intervention between the extrovert group and the introvert group (p = 0.004); (2) there were significant differences of VAS nocebo intervention between the extrovert group and the introvert group (p = 0.011); (3) there were significant differences between the VAS placebo intervention and VAS pain status (baseline) in both the extrovert group (p < 0.001) and the introvert group (p = 0.001); (4) there were significant differences between the VAS nocebo intervention and VAS pain status (baseline) in both the extrovert group (p = 0.008) and the introvert group (p < 0.001). Moreover, there were significant differences in the brain network for placebo and nocebo responses between different personalities. We found that (1) deactivation differences of the pain-related network and limbic system play an important role in personality differences associated with placebo analgesia and (2) differences of control of anxiety and activation of dorsolateral prefrontal cortex may cause the personality differences observed in nocebo hyperalgesia.
Highlights
As an important psychological response, the placebo effect and nocebo effect have attracted increasing attention from researchers [1, 2]
In the psychophysiological interaction (PPI) map of the rostral ACC (rACC), the results showed that compared with pain status (OFF block), placebo status (ON block) had decreased effective connectivity (EC) with the cerebellum posterior lobe (CPL), parahippocampal gyrus (PHP), IC, THS, dorsolateral prefrontal cortex (DLPFC), posterior cingulate cortex (PCC), and supplementary motor area (SMA) and increased EC with fusiform gyrus (FG)
In the PPI map of the rACC, the results showed that compared with pain status (OFF block), placebo status (ON block) had decreased EC with AMYG, middle temporal lobe (MTL), CPL, lingual gyrus (LG), HP, inferior temporal lobe (ITL), orbitofrontal cortex (OFC), angular gyrus (AG), pregenual anterior cingulate cortex, secondary somatosensory area (S2), SMA, DLPFC, ventromedial prefrontal cortex (VMPFC), and precuneus and increased EC with brainstem (BRS)
Summary
As an important psychological response, the placebo effect and nocebo effect have attracted increasing attention from researchers [1, 2]. Researchers found that if the subjects had a good expectation of an analgesic effect (placebo effect), there would be a better analgesic effect [5,6,7], whilst the nocebo effect is defined as the heightened pain response to a lowpain inducing and/or innocuous stimulus purported to increase pain or unpleasant symptoms [8]. Some scholars have suggested that the placebo analgesia effect is based on the opioid-mediated analgesia system (OMAS) [9,10,11], whilst the nocebo hyperalgesia effect. It is noteworthy that the above studies cannot fully study the placebo effect and nocebo effect brain network, which is based on the advanced neurological function of the brain [14]
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