Multiple confounders influence the association between low-grade systemic inflammation and musculoskeletal pain. A call for a prudent interpretation of the literature

Abstract

Our understanding of the multiple systems and their interactions that contribute to musculoskeletal pain has evolved considerably in recent years. There is a considerable interest in the role of the immune system in both acute and persistent musculoskeletal pain states [1], [2]. Systemically elevated levels of proinflammatory cytokines and chemokines have been revealed in people with musculoskeletal pain. This low-grade inflammation has been demonstrated in various musculoskeletal conditions, such as low back pain [1], neck pain [2], and radicular pain [3]. In addition, levels of inflammatory biomarkers are associated with pain severity in people with neck and shoulder pain [4] and low back pain [1]. Moreover, an initial study suggests that inflammatory responses in the acute phase of low back pain may also be related to recovery [5]. In people with and without musculoskeletal pain, levels of inflammatory biomarkers are influenced by multiple factors, such as demographic variables (eg, age and gender), lifestyle factors (eg, physical activity, saturated fat intake, and sleep quality), psychological factors (eg, depression and catastrophizing), and various diseases (eg, cardiovascular and osteoarthritis) [6–8]. These factors can increase systemic cytokine concentrations via their direct or indirect action on immune cells and the subsequent release of inflammatory cytokines and chemokines [7]. Therefore, adjustment for potential confounders is essential to determine the level of association between low-grade systemic inflammation, musculoskeletal pain, and recovery.