The relationships between proinflammatory cytokines and depressive symptoms in adolescents with chronic pain

Depressive symptoms and chronic pain commonly co-occur among adolescents and share similar proposed underlying processes, including elevation of proinflammatory cytokines. In this study, we investigate how profiles of 4 commonly measured proinflammatory cytokines (IL-1β, IL-6, IL-8, and TNF-α) differ between adolescents with primary chronic pain disorders and pain-free peers. We explored relationships between these cytokines and depressive symptoms, perceived distress (PD), pain severity, functional disability (FD), pain catastrophizing (Pcat), and fear of pain (FOP). Potential mediating effects of cytokines on the relationship between depressive symptoms and FD were also examined.

Differences in cytokine profiles between groups were compared through t-tests. Relationships between cytokine profiles and outcomes were assessed through partial correlations. Bootstrapping mediation analysis assessed whether cytokines mediated the relationship between depressive symptoms and functional disability. Our sample included 78 youth (chronic pain n = 54, Mage = 14 years; pain-free n = 24; Mage = 16 years).

We found that (1) IL-6 levels were higher among adolescents with chronic pain than pain-free peers; (2) higher IL-1β and IL-6 levels were associated with greater PD among adolescents with and without pain; (3) among the pain group, higher IL-6 levels were associated with greater PD, pain severity, and FD; (4) among the pain group, higher IL-1β levels were associated with greater depressive symptoms, PD, Pcat, and FOP. Mediation effects were not significant.

Our findings suggest that IL-1β and IL-6 play critical roles in the pain experience. Interleukin-6 is more strongly associated with physical symptoms, and IL-1β is more related to fear-avoidance.