An explorative cross-sectional study on the association between immunological biomarkers in patients with chronic pain.

Background: Studies indicate an association between pain perception and inflammatory response. However, the expression of inflammatory cytokines in the regulation of the interaction between pain and other coexisting symptoms related to pain, such as fatigue, remains largely unknown. Aim: This study utilizes a comprehensive screening method for inflammatory biomarkers to objectively study their relation to fatigue and other patient reported outcomes, such as depression and sleep disturbances, in a cohort entailing patients with chronic pain and controls reporting no pain. Material and methods: 36 patients with chronic pain and 36 healthy pain free controls were included. To investigate possible differences between patients and controls, the QUICKPLEX SQ 120 with a panel of 71 pro- and anti-inflammatory proteins was used. Patient reported data covering aspects of fatigue, fatigability, mood and sleep was also administered. Results: No apparent difference in abundance of inflammatory substances was found between patients and controls. Likewise, no association was between levels of inflammatory biomarkers and performance on objectively measured cognitive fatigability. However, an explorative multivariate PCA analysis with immunological response as the determinant revealed five specific clusters, two clusters of controls and three patient clusters. One patient cluster had an overall lower concentration level of inflammatory substances compared to the other clusters. This cluster reported higher levels of general fatigue (trait fatigue) and state fatigue as well as higher proportions of pain localizations, perceived helplessness, insomnia, depressive symptoms, and anxiety. Conclusion: This study underscores the complexity of pain perception and its interplay with inflammatory responses, as well as the individual experience of fatigue and other co-occurring symptoms. We argue that patients with chronic pain do not constitute a homogeneous group, and that simple patient-control comparisons may be insufficient to elucidate the underlying inflammatory processes involved. Our findings suggest that chronic pain patients who report higher levels of fatigue, sleep disturbances, and depressive symptoms might exhibit inflammatory response proteins associated with tissue-repair mechanisms. We speculate that this pattern could indicate a response driven more by central pain mechanisms.