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

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 1b 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 [...]