The purpose of this study was to perform a systematic review of the available literature on morphological and functional brain changes measured by modern neuroimaging techniques in patients suffering from chronic cancer-related pain. A systematic search was conducted in PubMed, Embase, and Web of Science using different keyword combinations. In addition, a hand search was performed on the reference lists and several databases to retrieve supplementary primary studies. Eligible articles were assessed for methodological quality and risk of bias and reviewed by two independent researchers. The search yielded only four studies, three of which used MRI and one PET-CT. None of the studies measured longitudinal morphological (i.e., gray or white matter) changes. All studies investigated functional brain changes and found differences in specific brain regions and networks between patients with chronic cancer-related pain and pain-free cancer patients or healthy volunteers. Some of these alterations were found in brain networks that also show changes in non-cancer populations with chronic pain (e.g., the default mode network and salience network). However, specific findings were inconsistent, and there was substantial variation in imaging methodology, analysis, sample size, and study quality. There is a striking lack of research on morphological brain changes in patients with chronic cancer-related pain. Moreover, only a few studies investigated functional brain changes. In the retrieved studies, there is some evidence that alterations occur in brain networks also involved in other chronic non-cancer pain syndromes. However, the low sample sizes of the studies, finding inconsistencies, and methodological heterogeneity do not allow for robust conclusions.
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