{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T06:09:06Z","timestamp":1789711746787,"version":"4.0.1"},"reference-count":87,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T00:00:00Z","timestamp":1789689600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Psychol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Traumatic experiences and dysfunctional emotional responses to pain modulate pain processing via partly different neural circuits. Modulation of pain experience by brain mechanisms is partly conveyed via descending pathways through the midbrain and brainstem. We designed an intervention study using Eye Movement Desensitization and Reprocessing (EMDR) to desensitize (a) distressing memories of adverse life events (ALE), or (b) pain-related anxiety and emotion dysregulation such as pain catastrophising (PCAT). Our primary objective is to examine the extent to which EMDR efficacy on pain severity and affective symptoms is mediated via these targeted risk factors. The secondary objective is to assess the mediational effects of brain functional and structural markers and functions of the pain modulation circuitry of the brainstem.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This study is a pre-post longitudinal trial with two parallel treatment arms in individuals with chronic primary or secondary pain syndromes. Primary outcomes and mediators of interest include measures of pain severity (intensity, interference, pain-related distress) and affective symptoms (anxiety, depression, tension, irritability) assessed at baseline and post-treatment. Secondary outcomes include structural and functional brain imaging (fMRI), smartphone-based ecological momentary assessment (EMA), biosampling (blood, stool), somatosensory testing (tender point count, quantitative sensory testing, pressure cuff algometry, nociceptive predictive processing) and self-reported measures on pain and affective symptoms. EMDR treatment will consist of six sessions over the course of 2 weeks. Outcome assessors will be blinded to treatment allocation. Mediational analyses will be conducted within a parallel mediation framework using structural equation modeling.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>This study aims to investigate the mechanism of how an EMDR intervention with one of two different foci influences clinical outcomes by mediation analysis. We hypothesize that (1) EMDR treatment focussing on ALE will lead to a decrease in pain severity and affective symptoms through a decrease in arousal symptoms and engagement of paraventricular thalamus and ventral striatum, and (2) that EMDR treatment focussing on pain-related anxiety and emotion dysregulation will lead to a decrease in pain severity and affective symptoms through a decrease in PCAT and strengthening of prefrontal-limbic and brainstem controls.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Clinical trial registration<\/jats:title>\n                    <jats:p>\n                      <jats:ext-link>https:\/\/www.drks.de<\/jats:ext-link>\n                      , identifier DRKS00039123.\n                    <\/jats:p>\n                  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