Local up-regulation of interferon-γ (IFN-γ) following disc herniation is involved in the inflammatory response underlying acute lumbar radicular pain.

Lumbar radicular pain after disc herniation may be associated with release of pro-inflammatory cytokines from nucleus pulposus (NP) tissue. In the present study we examined the role of interferon-γ (IFN-γ) and cluster of differentiation 68 (CD68) in the acute phase of this process. First, in an animal model mimicking the clinical situation after disc herniation, the role of IFN-γ close to the dorsal nerve roots was studied. Next, in patients with lumbar radicular pain due to disc herniation, we examined how two single nucleotide polymorphisms (SNPs; rs2069705 and rs2069718) are important for the IFN-γ expression influenced the pain behavior. The animal data demonstrated a significant increase in the nociceptive activity at the spinal level after local application of NP and IFN-γ onto the dorsal nerve roots. A positive correlation between IFN-γ and CD68 in the NP tissue was also demonstrated. In the patients, a significant increase in Oswestry Disability Index (ODI) score was observed in carriers of the IFN-γ SNPs; rs2069705 A and rs2069718 G alleles. The present data suggest that IFN-γ close to the dorsal nerve roots may contribute to the pathogenesis, the nociceptive activity and the pain behavior following lumbar disc herniation.

The interleukin-1α gene C>T polymorphism rs1800587 is associated with increased pain intensity and decreased pressure pain thresholds in patients with lumbar radicular pain.

OBJECTIVES: Previous studies have suggested that many inflammatory cytokines, including interleukin (IL)-1α, may be associated with lumbar radicular pain after disk herniation. In the present study, we examined how variability of the IL-1α gene affects pain intensity and the pressure pain threshold (PPT) in patients with symptomatic disk herniation. MATERIALS AND METHODS: A total of 121 patients with lumbar radicular pain due to disk herniation were recruited from Oslo University Hospital, Norway, and followed up at 6 weeks and 12 months. The primary outcome measures were pain intensity scores for the lower back and legs using a visual analog pain scale (VAS) and PPT for the gluteal muscles. Genotyping was carried out using a predesigned TaqMan assay for IL-1α rs1800587. The effect of the IL-1α genotype on the VAS and PPT was analyzed by repeated measure analyses of variance. RESULTS: The IL-1α gene C>T polymorphism rs1800587 affected VAS and PPT scores in patients with symptomatic disk herniation. Patients with the CT/TT genotype reported a higher VAS leg pain intensity (P=0.002) and also a lower PPT in the gluteal muscles (left P=0.016; right P=0.016) compared with patients with the CC genotype during 1 year of follow-up. DISCUSSION: The present data show that the IL-1α CT/TT genotype rs1800587 may be associated with increased pain intensity and corresponding reduced PPT during the first year after disk herniation.

The MMP1 rs1799750 2G allele is associated with increased low back pain, sciatica, and disability after lumbar disk herniation.

OBJECTIVES: Previous studies indicate that genetic variants in genes encoding proteins like matrix metalloproteinase (MMP) enzymes may affect degeneration of the intervertebral disk. One such genetic variant is a single nucleotide polymorphism insertion in the promoter region of the MMP1 gene, that is, the MMP1 rs1799750 2G allele, which increases the MMP1 expression in vitro. In this study, we examined whether the MMP1 rs1799750 2G allele might be associated with disk degeneration and clinical outcome after lumbar disk herniation. MATERIALS AND METHODS: A total of 260 patients with lumbar disk herniation and sciatic pain were included in this study and genotyped for the MMP1 rs1799750 2G allele. RESULTS: The present data showed no differences in the frequency of the MMP1 2G allele in patients recently diagnosed with disk herniation compared with pain-free controls. Moreover, in the patients, the MMP1 2G allele was not directly related to the disk degeneration. However, our data demonstrated that the MMP1 2G allele was associated with both pain and disability, that is, increased visual analog scale score, McGill Pain Questionnaire score, and Oswestry Disability Index score. Clearly, the patients homozygous for the 2G allele had more pain and reduced function compared with those carrying the 1G allele. DISCUSSIONS: Our findings suggest that the MMP1 rs1799750 2G/2G genotype may contribute to low back pain, sciatica, and disability after lumbar disk herniation.