not-yet-known not-yet-known not-yet-known unknown Background: Chronic musculoskeletal pain has been associated with changes at various levels regarding pain processing. One of the fields that has highlighted such differences between healthy individuals and people suffering from chronic musculoskeletal pain is neuroimaging of the brain. The mixed results arising from the different pathologies in addition to the use of different brain imaging modalities do not offer a conclusive overview, implicating the interpretation of the findings and their relevance as a causal or a consequent factor to chronification of pain. The aim of this systematic review is to provide a comprehensive summary of the available evidence assessing chronic painful conditions against healthy populations per functional neuroimaging modality. Methods: The protocol for this systematic review was informed and reported in line with the Preferred Reporting Items for Systematic Reviews. The databases that will be searched from inception to 8 January 2024 include PubMed, EMBASE (Ovid Interface), Scopus, Cochrane Library and Web of Science (Clarivate Analytics). Risk of bias will be assessed with the Newcastle-Ottawa tool, and the quality of the cumulative evidence assessed with the Grading of Recommendations, Assessment, Development and Evaluation guidelines. Discussion: The results of this review will provide an up-to-date report on what the main findings of brain neuroimaging per pathological population and imaging modality are, assessing at the same time the quality of the evidence and indicating future directions in the field of neuroimaging assessment of the musculoskeletal patient.