Placebo treatment affects brain systems related to affective and cognitive processes, but not nociceptive pain

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Placebo analgesia is a replicable and well-studied phenomenon, yet it remains unclear to what degree it includes modulation of nociceptive processes. Some studies find effects consistent with nociceptive effects, but meta-analyses show that these effects are often small. We analyzed placebo analgesia in a large fMRI study (N = 392), including placebo effects on brain responses to noxious stimuli. Placebo treatment caused robust analgesia in both conditioned thermal and unconditioned mechanical pain. Placebo did not decrease fMRI activity in nociceptive pain regions, including the Neurologic Pain Signature (NPS) and pre-registered spinothalamic pathway regions, with strong support from Bayes Factor analyses. However, placebo treatment affected activity in pre-registered analyses of a second neuromarker, the Stimulus Intensity Independent Pain Signature (SIIPS), and several associated a priori brain regions related to motivation and value, in both thermal and mechanical pain. Individual differences in behavioral analgesia were correlated with neural changes in both thermal and mechanical pain. Our results indicate that processes related to affective and cognitive aspects of pain primarily drive placebo analgesia.

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  1. 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.

  2. 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?

  3. 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.