Study design: Prospective longitudinal study.
Objective: To determine whether systemic cytokines and C-reactive protein (CRP) during an acute episode of low back pain (LBP) differ between individuals who did and did not recover by 6 months and to identify sub-groups based on patterns of inflammatory, psychological, and sleep features associated with recovery/non-recovery. Systemic inflammation is observed in chronic LBP and may contribute to the transition from acute to persistent LBP. Longitudinal studies are required to determine whether changes present early or develop over time. Psychological and/or sleep-related factors may be related.
Methods: Individuals within 2 weeks of onset of acute LBP (N = 109) and pain-free controls (N = 55) provided blood for assessment of CRP, tumor necrosis factor (TNF), interleukin-6 (IL-6) and interleukin-1β, and completed questionnaires related to pain, disability, sleep, and psychological status. LBP participants repeated measurements at 6 months. Biomarkers were compared between LBP and control participants at baseline, and in longitudinal (baseline/6 months) analysis, between unrecovered (≥pain and disability), partially recovered (reduced pain and/or disability) and recovered (no pain and disability) participants at 6 months. We assessed baseline patterns of inflammatory, psychological, sleep, and pain data using hierarchical clustering and related the clusters to recovery (% change in pain) at 6 months.
Results: CRP was higher in acute LBP than controls at baseline. In LBP, baseline CRP was higher in the recovered than non-recovered groups. Conversely, TNF was higher at both time-points in the non-recovered than recovered groups. Two sub-groups were identified that associated with more ("inflammatory/poor sleep") or less ("high TNF/depression") recovery.
Conclusions: This is the first evidence of a relationship between an "acute-phase" systemic inflammatory response and recovery at 6 months. High inflammation (CRP/IL-6) was associated with good recovery, but specific elevation of TNF, along with depressive symptoms, was associated with bad recovery. Depression and TNF may have a two-way relationship. These slides can be retrieved under Electronic Supplementary Material.
Keywords: C-reactive protein (CRP); Depression; Interleukin-1β (IL-1β); Interleukin-6 (IL-6); Longitudinal; Low back pain (LBP); Pro-inflammatory cytokines; Sleep; Systemic; Transition to chronicity; Tumor necrosis factor (TNF).