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An experimental investigation into the mediating role of pain-related fear in boosting nocebo hyperalgesia.

ABSTRACT: Nocebo hyperalgesia refers to increases in perceived pain that putatively result from negative expectations regarding a nocebo stimulus (eg, an inert treatment, compared with no treatment). The precise cognitive-emotional factors contributing to the origins of nocebo effects are poorly understood. We aimed to test the effects of experimentally induced pain-related fear on the acquisition and extinction of nocebo hyperalgesia in healthy participants (N = 72). Acquisition and extinction of nocebo hyperalgesia were compared between a group receiving standard nocebo conditioning (Control group) and 2 groups receiving distinct fear inductions: high intensity of pain stimulations (High-pain group) or a threat manipulation (High-threat group). During nocebo acquisition, the Control and High-threat groups were administered thermal pain stimulations of moderate intensity paired with sham electrical stimulation (nocebo trials), whereas high pain intensity was administered to the High-pain group. During extinction, equivalent pain intensities were administered across all trials. Pain-related fear was measured by eyeblink startle electromyography and self-report. Nocebo hyperalgesia occurred in all groups. Nocebo effects were significantly larger in the High-pain group than those in the Control group. This effect was mediated by self-reported fear, but not by fear-potentiated startle. Groups did not differ in the extinction rate. However, only the High-pain group maintained significant nocebo responses at the end of extinction. Anticipatory pain-related fear induced through a threat manipulation did not amplify nocebo hyperalgesia. These findings suggest that fear of high pain may be a key contributor to the amplification of nocebo hyperalgesia, only when high pain is experienced and not when it is merely anticipated.

SUBMITTER: Thomaidou MA

PROVIDER: S-EPMC7737877 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

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An experimental investigation into the mediating role of pain-related fear in boosting nocebo hyperalgesia.

Thomaidou Mia Athina MA Veldhuijzen Dieuwke Swaantje DS Meulders Ann A Evers Andrea Walburga Maria AWM

Pain 20210101 1

Nocebo hyperalgesia refers to increases in perceived pain that putatively result from negative expectations regarding a nocebo stimulus (eg, an inert treatment, compared with no treatment). The precise cognitive-emotional factors contributing to the origins of nocebo effects are poorly understood. We aimed to test the effects of experimentally induced pain-related fear on the acquisition and extinction of nocebo hyperalgesia in healthy participants (N = 72). Acquisition and extinction of nocebo ...[more]

PMID: 32910630

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Project description:BackgroundPlacebo and nocebo responses have been increasingly gaining the attention of clinical and scientific researchers. Inconsistent conclusions from current studies indicate that different factors potentially affect both placebo and nocebo responses. Increasing evidence suggests that personality differences may affect the mechanisms of both two responses. In the present work, we explored the characteristics of neural signals of placebo and nocebo responses based on functional connectivity (FC) analysis and Granger causality analysis (GCA).MethodsA total of 34 healthy participants received conditional induction training to establish placebo and nocebo responses. Every participant completed the following experimental workflow, including scanning of baseline, experimental low back pain model establishment, scanning of acute pain status, and scanning of placebo response or nocebo response. We collect visual analogue scale (VAS) data after each scanning. Functional magnetic resonance imaging (fMRI) data from different personality groups were subjected to FC analysis and multivariate GCA (mGCA).ResultsPain scores for placebo and nocebo responses were statistically different across different personality. There are also statistically differences in the neural signals of two responses across different personality.ConclusionsThe findings of the present study indicated that extroverted and introverted participants are likely to experience placebo analgesic effects and nocebo hyperalgesia effects, respectively. Both extroverted and introverted participants showed significant changes in brain networks under placebo response. Variation in emotional control and ventromedial prefrontal cortex inactivity may constitute the bulk of the personality differences in placebo analgesia. Differences in the regulation of the sensory conduction system (SCS) and release of the emotional circuit could be important factors affecting personality differences in nocebo hyperalgesia.

Dataset Information

An experimental investigation into the mediating role of pain-related fear in boosting nocebo hyperalgesia.

Publications

An experimental investigation into the mediating role of pain-related fear in boosting nocebo hyperalgesia.

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