European Spine Journal

, Volume 27, Issue 4, pp 763–777 | Cite as

ISSLS PRIZE IN CLINICAL SCIENCE 2018: longitudinal analysis of inflammatory, psychological, and sleep-related factors following an acute low back pain episode—the good, the bad, and the ugly

  • David M. Klyne
  • Mary F. Barbe
  • Wolbert van den Hoorn
  • Paul W. HodgesEmail author
Original Article


Study design

Prospective longitudinal study.


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.

Summary of background data

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.


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.


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.


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.

Graphical abstract

These slides can be retrieved under Electronic Supplementary Material.


Pro-inflammatory cytokines C-reactive protein (CRP) Tumor necrosis factor (TNF) Interleukin-6 (IL-6) Interleukin-1β (IL-1β) Systemic Depression Sleep Low back pain (LBP) Longitudinal Transition to chronicity 


Funding information

This research was funded by the National Health and Medical Research Council (NHMRC) of Australia (Program Grant: ID631717; Project Grant ID631369). PWH supported by NHMRC Fellowship ID1002190. The manuscript submitted does not contain information about medical device(s)/drug(s).

Compliance with ethical standards

Conflict of interest

There are no conflicts of interest related to this work.

Ethical approval

Approved by The University of Queensland Institutional Medical Research Ethics Committee.

Supplementary material

586_2018_5490_MOESM1_ESM.pptx (418 kb)
Supplementary material 1 (PPTX 417 kb)


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • David M. Klyne
    • 1
  • Mary F. Barbe
    • 2
  • Wolbert van den Hoorn
    • 1
  • Paul W. Hodges
    • 1
    Email author
  1. 1.NHMRC Centre of Clinical Research Excellence in Spinal Pain, Injury and Health, School of Health and Rehabilitation SciencesThe University of QueenslandBrisbaneAustralia
  2. 2.Department of Anatomy and Cell Biology, Temple University School of MedicineTemple UniversityPhiladelphiaUSA

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