Brain mechanisms supporting mindfulness-based chronic pain relief: A randomized, sham-mindfulness meditation controlled mechanistic clinical trial protocol.

Introduction: Chronic low back pain (cLBP) is a leading cause of disability worldwide and is frequently refractory to pharmacological treatment. Mindfulness meditation has been shown to reduce pain through modulation of self-referential, cognitive and affective mechanisms. However, the neural mechanisms supporting the direct and immediate modulation of movement-evoked cLBP by mindfulness meditation as compared to an appropriate placebo-control remain poorly characterized. Methods and analysis: This single-center, sham-mindfulness meditation-controlled mechanistic clinical trial randomized 120 meditation naïve adults with cLBP to a six-session (20 min/session) mindfulness meditation, sham-mindfulness meditation, or book-listening control intervention delivered over two weeks. Perfusion fMRI was acquired at pre- and post-intervention timepoints during pain evocation with the leg raise test (LRT), a standardized orthopedic maneuver used to evoke low back and/or radiating leg pain in individuals with lumbar pathology. The primary outcome was change in whole-brain cerebral blood flow. Secondary outcomes included change in numerical pain ratings (0 = no pain; 10 = worst pain imaginable) corresponding to the LRT. Planned analyses include mixed-effects models examining group-by-time effects on behavioral and neuroimaging outcomes.

Discussion: By integrating a clinically relevant movement-evoked pain paradigm with perfusion-based neuroimaging and a matched sham meditation control, this trial will isolate mindfulness-specific neural mechanisms underlying pain modulation to inform the design of future efficacy-focused clinical trials. Ethics and dissemination: The study (ClinicalTrials.gov identifier: NCT03354585) was approved by the University of California, San Diego Institutional Review Board (IRB#181814). Written informed consent was obtained from all participants. At the time of manuscript submission, recruitment and intervention delivery were complete and data analyses ongoing. Study findings will be disseminated through peer-reviewed publications and scientific conferences.