Spinal nociceptive hyperexcitability induced by experimental disc herniation is associated with enhanced local expression of Csf1 and FasL

Pain. 2013 Sep;154(9):1743-1748. doi: 10.1016/j.pain.2013.05.034. Epub 2013 May 24.


Sciatica after disc herniation may be associated with compression of spinal nerves, but also inflammatory substances released from the nucleus pulposus (NP) leaking into the spinal canal. Here, in an animal model mimicking clinical intervertebral disc herniation, we investigate the effect of NP on neuronal activity. In anaesthetized Lewis rats, extracellular single-unit recordings of spinal dorsal horn neurons were performed, and the C-fibre responses were examined. Moreover, quantitative polymerase chain reaction was used to explore the gene expression of proinflammatory cytokines in the NP tissue exposed to the spinal dorsal nerve roots L3-L5. In accordance with earlier studies, we showed a significant increase in the C-fibre response and an upregulation of the gene expression of interleukin 1β and tumour necrosis factor 180 minutes after application of NP onto the nerve roots. Moreover, based on a polymerase chain reaction array of 84 common inflammatory cytokines at the same time point, we demonstrated a highly significant upregulation of colony-stimulating factor 1 also termed macrophage colony-stimulating factor and Fas ligand. The pronounced upregulation of Csf1 and Fas ligand 180 minutes after application of NP onto the nerve roots suggests that macrophage activation and apoptosis may be involved in pain hypersensitivity and other sensory abnormalities after disc herniation.

Keywords: C-fibre response; Csf1; FasL; Glial cells; L1β; M-CSF; Nucleus pulposus; Proinflammatory cytokines; Sensitization; TNF.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Action Potentials
  • Animals
  • Cytokines / metabolism
  • Disease Models, Animal
  • Electric Stimulation
  • Fas Ligand Protein / metabolism*
  • Female
  • Gene Expression Regulation / physiology*
  • Intervertebral Disc Displacement / complications*
  • Macrophage Colony-Stimulating Factor / metabolism*
  • Pain / etiology*
  • Pain / pathology*
  • Posterior Horn Cells / physiology
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Inbred Lew
  • Sciatic Nerve / physiology
  • Spinal Cord / metabolism*
  • Spinal Cord / pathology*
  • Time Factors
  • Tumor Necrosis Factor-alpha / genetics
  • Tumor Necrosis Factor-alpha / metabolism


  • Cytokines
  • Fas Ligand Protein
  • RNA, Messenger
  • Tumor Necrosis Factor-alpha
  • Macrophage Colony-Stimulating Factor