Mindfulness meditation and placebo modulate distinct multivariate neural signatures to reduce pain

Background:
Rather than a passive reflection of nociception, pain is shaped by the interplay between one's experiences, current cognitive-affective states, and expectations. The placebo-response, a paradoxical yet reliable phenomenon, is postulated to reduce pain by engaging mechanisms shared with "active" therapies. It has been assumed that mindfulness meditation, practiced by sustaining nonjudgmental awareness of arising sensory events, merely reflects mechanisms evoked by placebo. Recently, brain-based multivariate pattern analysis (MVPA) has been validated to successfully disentangle nociceptive-specific, negative-affective, and placebo-based dimensions of the subjective pain experience.

Methods:
To determine if mindfulness meditation engages distinct brain mechanisms from placebo and sham-mindfulness to reduce pain, MVPA pain signatures were applied across two randomized clinical trials that employed overlapping psychophysical pain testing procedures (49°C noxious heat; visual analogue pain scales) and distinct fMRI techniques (blood-oxygen-level dependent; perfusion-based). After baseline pain testing, 115 healthy participants were randomized into a four-session mindfulness meditation (n = 37), placebo-cream conditioning (n = 19), sham-mindfulness meditation (n = 20), or book-listening (n = 39) intervention. After each intervention, noxious heat was administered during fMRI and each manipulation.

Results:
A double dissociation in the MVPA signatures supporting pain regulation was revealed by mindfulness meditation as compared to placebo-cream. Mindfulness meditation produced significantly greater reductions in pain intensity and pain unpleasantness ratings, nociceptive-specific and negative-affective pain signatures when compared to placebo-cream, sham-mindfulness meditation and controls. Placebo-cream only reduced the placebo-based signature.

Conclusions:
Mindfulness meditation and placebo engage distinct neural pain signatures to reduce pain to demonstrate mechanistic granularity between placebo and mindfulness.

Keywords: MVPA; fMRI; meditation; mindfulness; pain; placebo.

PMID: 39216636 DOI: 10.1016/j.biopsych.2024.08.023