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

• Sciatica following disc herniation may be associated with compression of spinal nerves, but also by 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, qPCR was used to explore the gene expression of pro-inflammatory 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 up-regulation of the gene expression of interleukin 1β (IL1β) and tumour necrosis factor (TNF) 180 minutes after application of NP onto the nerve roots. Moreover, based on a PCR array of 84 common inflammatory cytokines at the same time point, we demonstrated a highly significant up-regulation of colony-stimulating factor 1 (Csf1) also termed macrophage colony-stimulating factor (M-CSF) and Fas ligand (FasL). The pronounced up-regulation of Cfs1 and FasL 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 following disc herniation.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Ortopedi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Orthopaedics (hsv//eng)

Nyckelord

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

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