A Study Of The Brain Network Mechanism Of The Placebo Analgesia And Nocebo Hyperalgesia

Background and ObjectivePlacebo analgesia and nocebo hyperalgesia effects are increasingly concerned by clinical and scientific researchers,but current studies based on functional brain imaging have not reached a consistent conclusion,suggesting that the placebo response and nocebo response are affected by different factors and lead to different conclusions.More and more evidences show that there are gender and personality differences in the brain networks of placebo analgesia and nocebo hyperalgesia,suggesting that gender and personlity are the important factors that affecting the effects of placebo response and nocebo response.It is hopeful to draw a consistent conclusion on the gender or personality classification of subjects,and few studies have been published in this field.The purpose of this study was to explore the differences of functional magnetic resonance imaging(fMRI)signals between different genders or personalities at similar baseline pain status.Meanwhile,the characteristics of'brain network signals in placebo response and nocebo response were comprehensively explored by using functional connectivity(FC)analysis and Granger causality analysis(GCA).MethodsAll 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,4)pseudo-random scanning of placebo response or nocebo response.Behavioral data were collected after each scan.Based on the FC analysis,multivariate GCA and behavioral correlation analysis,the fMRI data of different genders or personalities groups were analyzed.ResultsThe results showed that the pain scores of placebo response and nocebo response were statistically different between different genders,as well as between the different personalities.At the same time,there were significant differences of brain network of placebo response and nocebo response between different genders,as well as between the different personalities.ConclusionsIn this study,we classified the subjects based on gender and personality factors,and then collected behavioral data and brain functional imaging data.Methods such as FC analysis,GCA and correlation analysis were used to analyze the fMRI data.After discussion and summary,the following conclusions were drawn:In this study,we found that male subjects were more likely to produce placebo analgesic effect and female subjects were more likely to produce nocebo hyperalgesia effect.At the same time,we found that extrovert subjects were more likely to produce placebo analgesic effect while introvert subjects were more likely to produce nocebo hyperalgesia effect.Both male and female subjects had decreased activity of pain matrix under the placebo response,while the pain matrix was activated under the nocebo response.The differences in activation of opioid system and reward system may be the main reason for the differences between male and female subjects in placebo response,while the differences in formation of negative emotions and the positive regulation of limbic system may be the important factors for the gender differences in nocebo response.Both extrovert and introvert subjects showed significant changes in brain network under the placebo response.The differences in emotional control and inactivity of ventromedial prefrontal cortex may be the main reasons for personality differences in placebo analgesia,while the differences in regulation of sensory conduction system and release of emotional circuit may be the important factor for personality differences in nocebo hyperalgesia.We found that the brain network characteristics of subjects with different genders or personalities have some similarities,but not the same.At the same time,we verified our hypothesis that the brain networks of placebo response and nocebo response are not only overlapping but also relative independent,that is,some key brain areas of two networks are the same,but they have various unique characteristics.