Low back pain and sciatica after disc herniation may be caused by mechanical compression of the nerve roots, but also by the release of inflammatory substances from nucleus pulposus (NP) of the herniated disc. In the present study the functional changes in the nociceptive signaling due to disc herniation and genetic factors important for persistent low back pain and sciatica were investigated.
First, in an animal model, single-unit recordings in the spinal dorsal horn were performed to investigate the effect of NP tissue on neuronal excitability, and to examine if this effect was affected by administration of an interleukin (IL)-1 receptor antagonist (IL-1Ra). Moreover, to identify potential up-regulated genes in NP tissue exposed to the spinal dorsal nerve roots, the gene expression of 84 cytokines in NP tissue was examined by a PCR array. The present data demonstrated that application of NP onto the spinal dorsal nerve roots enhanced dorsal horn neuronal excitability, but no clear effect of the IL-Ra was observed. A significant up-regulation in the gene expression of Colony stimulating factor-1 (Csf-1) and Fas ligand (Faslg) was observed in NP tissue exposed to the spinal dorsal nerve roots. Second, the association between genetic variation in pro-inflammatory cytokines and persistent low back pain and sciatica was examined in disc herniated patients (n=258). Pain and disability were measured by visual analogue scale (VAS), McGill sensory questionnaire and Oswestry disability index (ODI) over 12 months and the patients were genotyped with regard to IL-1α rs1800587, IL-1RN rs2234677, CSF-1 rs484959 and FASLG rs763110. The present findings revealed that carriers of IL-1α T allele in combination with IL-1RN A allele had more pain and slower recovery than other patients the first year after disc herniation. Hence, our findings suggest that the clinical outcome following disc herniation may be dependent upon IL-1α and IL-1RN genotypes. However, the data did not reveal any clear association between the CSF-1 or FASLG genotypes and the progression of pain and disability. Taken together, our data supports the hypothesis that pro-inflammatory cytokines are involved in the genesis of long lasting pain following disc herniation.