CCL25 in the cerebrospinal fluid is negatively correlated with fatigue in chronic pain patients

In this exploratory study of immune profiles in chronic pain cohorts awaiting surgery, the importance of BBB dynamics on serum-CSF cytokine dynamics, and to a lesser extent on central levels of cytokines, is highlighted. Surprisingly, there were no associations between any cytokines in serum or CSF and sleep disturbance, despite a high prevalence of clinically significantly disturbed sleep. In contrast, several associations between general fatigue and cytokine levels in both serum and CSF were found. Cytokines of note are CXCL11 and CCL25 in the CSF, especially because of their direct functional association. CXCL11 has been found to exert neuroprotective effects in animal models, while CCL25 is known as a proinflammatory cytokine and is the only cytokine to fall out as a significant negative contributor to degree of fatigue. While causality cannot be addressed, the negative correlation between CCL25 and fatigue in both univariate and multivariate analyses implies that neuroimmune activity might have an ameliorating effect on the degree of fatigue. This study further adds to existing evidence that centrally acting cytokines are associated with severity of symptomatology, and highlights that pain and fatigue seem to have slightly different cytokine profiles. Sleep disturbance needs to be further addressed, ideally using both subjective and objective assessment methods. CCL25 and CXCL11 are interesting biomarkers for future research on pain and associated symptoms.