{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T13:56:58Z","timestamp":1791381418697,"version":"4.3.3"},"reference-count":32,"publisher":"BMJ","issue":"10","license":[{"start":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T00:00:00Z","timestamp":1791331200000},"content-version":"unspecified","delay-in-days":6,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"HORIZON EUROPE Research and Innovation Programme","award":["Grant Agreement N\u00ba 101057367"],"award-info":[{"award-number":["Grant Agreement N\u00ba 101057367"]}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["BMJ Open"],"accepted":{"date-parts":[[2026,9,11]]},"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Pain is one of the most prevalent and disabling oncological symptoms, but its underlying mechanisms remain poorly understood. Most research has focused on peripheral mechanisms, while central pain modulation has been poorly explored. Quantitative sensory testing (QST) and electroencephalography (EEG) provide non-invasive approaches to assess central pain processing but the evidence using those approaches in patients with cancer is limited. This study protocol aims to identify and validate central biomarkers of pain perception and modulation (QST and EEG) and the role of moderator variables to better characterise patients with cancer pain.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and analysis<\/jats:title>\n                    <jats:p>This study protocol describes a multicentre, cross-sectional, case\u2013control study that will include a minimum of 470 ambulatory patients with cancer, including 313 with oncological pain and 157 without pain. Participants will be recruited taking into account age, sex and cancer type (lung, breast, pancreas, prostate and colon). All participants will perform a single face-to-face assessment that will include sociodemographic and clinical data, QST (pain modulation and inhibitory pain mechanisms, temporal summation and pain thresholds) and EEG (at rest and in response to thermal nociceptive stimuli) assessment and administration of questionnaires (pain, quality of life, fatigue, sleep, mood, etc). Statistical modelling and machine learning approaches will be used to investigate pain modulation biomarkers, their association with age and sex and to characterise patients with cancer pain.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Ethics and dissemination<\/jats:title>\n                    <jats:p>This study has received approval from all local ethics committees of the participating clinical sites. Results will be disseminated through high-impact peer-reviewed journals, international conferences and open data repositories, in compliance with General Data Protection Regulation (GDPR) and FAIR (Findable, Accessible, Interoperable, and Reusable) principles, and following the STROBE (Strengthening the Reporting of Observational Studies in Epidemiology) statement for observational case\u2013control studies.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial registration number<\/jats:title>\n                    <jats:p>\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"isrctn\" xlink:href=\"ISRCTN35887998\">ISRCTN35887998<\/jats:ext-link>\n                      .\n                    <\/jats:p>\n                  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