Placebo treatment affects brain systems related to affective and cognitive processes, but not nociceptive pain
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Abstract
Drug treatments for pain often do not outperform placebo, and a better understanding of placebo mechanisms is needed to improve treatment development and clinical practice. In a large-scale fMRI study ( N = 392) with pre-registered analyses, we tested whether placebo analgesic treatment modulates nociceptive processes, and whether its effects generalize from conditioned to unconditioned pain modalities. Placebo treatment caused robust analgesia in conditioned thermal pain that generalized to unconditioned mechanical pain. However, placebo did not decrease pain-related fMRI activity in brain measures linked to nociceptive pain, including the Neurologic Pain Signature (NPS) and spinothalamic pathway regions, with strong support for null effects in Bayes Factor analyses. In addition, surprisingly, placebo increased activity in some spinothalamic regions for unconditioned mechanical pain. In contrast, placebo reduced activity in a neuromarker associated with higher-level contributions to pain, the Stimulus Intensity Independent Pain Signature (SIIPS), and affected activity in brain regions related to motivation and value, in both pain modalities. Individual differences in behavioral analgesia were correlated with neural changes in both modalities. Our results indicate that cognitive and affective processes primarily drive placebo analgesia, and show the potential of neuromarkers for separating treatment influences on nociception from influences on evaluative processes.
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In many cases, rather than across domains, placebo effects may transfer between modalities and stimuli within the same domain (e.g., between thermal and mechanical pain, but not from pain to itch 91)
For pain vs itch specifically, it would be interesting to hear how your predictions about cross-modality placebo effects were adjusted based on the results of the current study.
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First, participants were introduced to the same cream, once presented as “Prodicaine, an effective pain-relieving drug” and once presented as “a control cream with no effects”.
How do you think the findings of this paper would be similar or different if the placebo were a different modality than a cream, say something injected, or would that not have been possible because of the study design?
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Throughout history, placebo effects have been variously considered as mysterious healing forces and tricks played upon the gullible by medical practitioners.
This is a really interesting paper, and as someone outside of the field, I appreciate the clear and compelling background section.
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