Neural mechanisms underlying placebo and nocebo effects in tonic muscle pain
Min Chen,
Xiao Wu,
Libo Zhang,
Fengrui Zhang,
Linling Li,
Yingying Zhang,
Donglin Xiong,
Yunhai Qiu,
Li Hu,
Weibo Xiao
Affiliations
Min Chen
Department of Anesthesiology, Shenzhen Samii Medical Center, Guangdong Province, China
Xiao Wu
CAS Key Laboratory of Behavioral Science, Institute of Psychology, Chinese Academy of Sciences, Beijing, China; Department of Psychology, University of Chinese Academy of Sciences, Beijing, China; CAS Key Laboratory of Mental Health, Institute of Psychology, Chinese Academy of Sciences, Beijing, China
Libo Zhang
Department of Psychology, University of Chinese Academy of Sciences, Beijing, China; CAS Key Laboratory of Mental Health, Institute of Psychology, Chinese Academy of Sciences, Beijing, China
Fengrui Zhang
Department of Psychology, University of Chinese Academy of Sciences, Beijing, China; CAS Key Laboratory of Mental Health, Institute of Psychology, Chinese Academy of Sciences, Beijing, China
Linling Li
Research Center for Neural Engineering, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Guangdong Province, China
Yingying Zhang
Department of Anesthesiology, Loudi Central Hospital, Hunan Province, China
Donglin Xiong
Department of Neurology, Loudi Central Hospital, Hunan Province, China
Yunhai Qiu
Research Center for Neural Engineering, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Guangdong Province, China
Li Hu
Department of Psychology, University of Chinese Academy of Sciences, Beijing, China; CAS Key Laboratory of Mental Health, Institute of Psychology, Chinese Academy of Sciences, Beijing, China; Corresponding authors.
Weibo Xiao
Department of Neurology, Loudi Central Hospital, Hunan Province, China; Department of Pain, Nanshan Hospital of Shenzhen City, Guangdong Medical College, Guangdong Province, China; Corresponding authors.
Pain is a highly subjective and multidimensional experience, significantly influenced by various psychological factors. Placebo analgesia and nocebo hyperalgesia exemplify this influence, where inert treatments result in pain relief or exacerbation, respectively. While extensive research has elucidated the psychological and neural mechanisms behind these effects, most studies have focused on transient pain stimuli. To explore these mechanisms in the context of tonic pain, we conducted a study using a 15-minute tonic muscle pain induction procedure, where hypertonic saline was infused into the left masseter of healthy participants. We collected real-time Visual Analogue Scale (VAS) scores and functional magnetic resonance imaging (fMRI) data during the induction of placebo analgesia and nocebo hyperalgesia via conditioned learning. Our findings revealed that placebo analgesia was more pronounced and lasted longer than nocebo hyperalgesia. Real-time pain ratings correlated significantly with neural activity in several brain regions. Notably, the putamen was implicated in both effects, while the caudate and other regions were differentially involved in placebo and nocebo effects. These findings confirm that the tonic muscle pain paradigm can be used to investigate the mechanisms of placebo and nocebo effects and indicate that placebo analgesia and nocebo hyperalgesia may have more distinct than common neural bases.
