Michael Kushnick

Purpose Proinflammatory cytokines play a critical role in chronic inflammation and pain and contribute to behavioral symptoms (depressive symptoms, anxiety, fatigue, sleep disturbance) and comorbidities (diabetes, cardiac diseases, cancer). Evidence is lacking on the specific proinflammatory cytokines associated with these behavioral symptoms/comorbidities co-occurring with axial low back pain (aLBP). This review aimed to systematically analyze the following: (1) specific proinflammatory cytokines associated with aLBP in adults, (2) associations among proinflammatory cytokines and behavioral symptoms in aLBP, and (3) relationships among proinflammatory cytokines and comorbidities in aLBP, to develop a new clinical framework for future diagnostic and intervention targets for patients with aLBP. Methods Electronic databases, including PubMed/MEDLINE, ProQuest Nursing & Allied Health Source, and CINAHL Complete (EBSCO) were searched for the period January 2012 to February 2023. Eligible studies included cross-sectional, case-control, longitudinal, and cohort studies in which proinflammatory cytokines were reported in adults above 18 years with aLBP. Intervention studies and randomized controlled trails were excluded. The Joanna Briggs Institute (JBI) criteria were used for quality evaluation. Results Findings from 11 studies showed 3 proinflammatory cytokines associated with pain intensity in adult patients with aLBP: C-Reactive Protein (CRP), Tumor Necrosis Factor (TNF-α), and Interleukin (IL-6). Some studies assessed associations between proinflammatory cytokines and depressive symptoms; none explored the association of proinflammatory cytokines with fatigue, anxiety, sleep disturbance, or comorbidities (diabetes, cardiac diseases, and cancer) in aLBP. Conclusions Proinflammatory cytokines in aLBP can serve as composite biomarkers for pain, associated symptoms, and comorbidities and may serve as a target for future interventions. There is need for well-designed studies assessing associations among chronic inflammation, behavioral symptoms, and comorbidities.