Wielgosz · The American journal of psychiatry 2022 · randomized active-control trial · n=145

Neural Signatures of Pain Modulation in Short-Term and Long-Term Mindfulness Training: A Randomized Active-Control Trial.

Level 2 - randomized trial

Individual randomized controlled trial with an active control group

PubMed 35899379 · doi:10.1176/appi.ajp.21020145 · record verified 2026-08-26

What was done

Healthy participants (N=115) underwent functional neuroimaging during an acute thermal pain task before and after random assignment to Mindfulness-Based Stress Reduction (MBSR, n=28), an active control Health Enhancement Program (HEP, n=32), or a waiting-list control condition (n=31). A non-randomized cohort of long-term meditators (n=30) completed the same imaging paradigm. Primary outcomes were self-reported pain intensity and unpleasantness, plus two multivoxel fMRI pain signatures: the Neurologic Pain Signature (NPS, nociceptive pain processing) and the Stimulus Intensity Independent Pain Signature-1 (SIIPS1, neuromodulatory pain processing).

What was found

MBSR significantly reduced NPS response compared to HEP (Cohen's d = -0.43) and from pre- to post-intervention (d = -0.47). Marginal decreases occurred for MBSR versus waiting list on NPS (d = -0.36), and on SIIPS1 versus both HEP (d = -0.37) and waiting list (d = -0.37). Subjective unpleasantness was reduced in both MBSR (d = -0.45) and HEP (d = -0.55) relative to waiting list. Long-term meditators reported lower pain than nonmeditators without baseline neural differences; within this group, retreat practice correlated with reduced SIIPS1 (r = -0.65), whereas daily practice did not.

Why it matters

This study provides evidence that an 8-week mindfulness intervention selectively reduces nociceptive-specific neural signatures beyond non-specific active control effects. It also suggests that intensive retreat practice engages distinct stimulus-independent modulatory pathways.

Limits

The randomized portion evaluated acute experimental thermal pain in healthy volunteers, limiting generalizability to chronic pain conditions. Sample sizes per randomized arm were relatively small (n=28 to 32), and the long-term meditator analysis was cross-sectional and observational.

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