European Spine Journal

, Volume 27, Issue 8, pp 1744–1756 | Cite as

Macrophage polarization contributes to local inflammation and structural change in the multifidus muscle after intervertebral disc injury

  • Gregory James
  • Kathleen A. Sluka
  • Linda Blomster
  • Leanne Hall
  • Annina B. Schmid
  • Cindy C. Shu
  • Christopher B. Little
  • James Melrose
  • Paul W. Hodges
Original Article



Intervertebral disk (IVD) lesion and its subsequent degeneration have a profound effect on the multifidus muscle. The subacute/early chronic phase of multifidus remodeling after IVD lesion has been proposed to be regulated by inflammatory processes. The balance between pro-inflammatory (M1) and anti-inflammatory (M2) macrophages plays an important role in maintaining tissue integrity after injury. The localization, polarization of macrophage subtypes and their mediation of the pro-inflammatory cytokine tumor necrosis factor (TNF) are unknown in paraspinal muscles during IVD degeneration. A sheep model of IVD degeneration was used to investigate the role of macrophages and TNF in the structural alterations that occur within the multifidus muscle.


Anterolateral lesions were induced at L3–4 IVD in sheep. Multifidus muscle tissue at L4 was harvested 3 and 6 months after lesion and used for immunofluorescence assays to examine total macrophage number, macrophage polarization between M1 and M2, and to assess the localization of TNF expression in muscle, adipose and connective tissues from injured and naïve control animals.


A greater proportion of M1 macrophages is present in muscle at both 3 and 6 months after IVD lesion, and adipose tissue at 6 months. Total number of macrophages is unchanged. At 6 months, expression of TNF is increased in adipose and connective tissue and the proportion of TNF expressed by M1 macrophages is increased.


These data support the proposal that macrophages and TNF (pro-inflammatory cytokine) play an active role in the subacute/early chronic phase of remodeling in muscle, adipose and connective tissues of the multifidus during IVD degeneration. This presents a novel target for treatment.

Graphical abstract

These slides can be retrieved under Electronic Supplementary Material.


Macrophage Multifidus muscle IVD lesion Pro-inflammatory TNF Adipose 



PWH has a Senior Principal Research Fellowship from the National Health and Medical Research Council (NHMRC) of Australia (APP1002190). The study was funded by a NHMRC Program Grant (ID631717) and Project Grant (APP1004032). The funding source did not play a role in investigation.

Compliance with ethical standards

Conflict of interest

Outside of this study, Kathleen A. Sluka recieved research funding from Medtronic, Inc, consultancy fees from Bayer Inc. and a book honorarium from IASP Press. The other authors declare they have no conflicts of interest.

Supplementary material

586_2018_5652_MOESM1_ESM.pptx (857 kb)
Supplementary material 1 (PPTX 856 kb)


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Copyright information

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

Authors and Affiliations

  • Gregory James
    • 1
  • Kathleen A. Sluka
    • 2
  • Linda Blomster
    • 1
  • Leanne Hall
    • 1
  • Annina B. Schmid
    • 1
    • 5
  • Cindy C. Shu
    • 3
  • Christopher B. Little
    • 3
  • James Melrose
    • 3
    • 4
  • Paul W. Hodges
    • 1
  1. 1.Centre of Clinical Research Excellence in Spinal Pain, Injury and Health, School of Health and Rehabilitation SciencesUniversity of QueenslandBrisbaneAustralia
  2. 2.Department of Physical Therapy and Rehabilitation ScienceUniversity of IowaIowa CityUSA
  3. 3.Raymond Purves Bone and Joint Research Laboratories, Kolling Institute of Medical Research, Institute of Bone and Joint Research, The Royal North Shore HospitalUniversity of SydneySt LeonardsAustralia
  4. 4.Graduate School of Biomedical EngineeringUniversity of New South WalesSydneyAustralia
  5. 5.Nuffield Department of Clinical NeurosciencesOxford UniversityOxfordUK

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