It is still unknown the pathogenesis of low back pain and a lot of hypothesis were discussed for a long time. Because non-invasive imaging modalities greatly underestimate the prevalence of epidural pathogenesis an endoscopic examination of the epidural space has been advocated as both a diagnostic and therapeutic modality. It seems that immune-inflammatory factors play a more substantial role in pain status. Myeloscopic investigation have shown how morphological pictures of the epidural area in patients with chronic low back pain (CLBP) are much more complex and heterogeneous than what can be identified with traditional investigation suggesting a biochemical involvement. Endoscopy of the epidural space (epiduroscopy) is a minimally invasive technique, used to directly visualize pathological features inside of the lumbar spinal canal to locate tissues responsible of eliciting pain and the presence of any pathological structures within the vertebral channel, such as fibrous adherences, inflammatory processes, severe fibrosis and/or stenoses, in order to realize an effective therapeutic approach in a lot of different CLBP status as those due to spinal stenoses or failed back surgery syndrome. To deepen the molecular causes of interindividual variability of epiduroscopy outcomes in terms of decrease of pain, it is useful to analyze the DNA variants encoding IL6 and IL1 cytokines and to relate them with gene expression levels and with the cytokine dosage. By this technique, it is possible to analyze in the biopsy of the epidural tissue the specific expression of the cytokines: there is already evidence that inflammatory factors may be involved in the genesis of LBP. At this regards, it would be really important to compare systemic cytokine levels before the epiduroscopy with those detected immediately post procedure and after one month, to understand if the cytokines could play a key role and be a biomarker of the epiduroscopy outcome. Concerning DNA polymorphisms, it has been demonstrated, in many disease-state meta-analyses, that the IL6 variant rs1800795 affect gene transcription and influences the IL-6 levels. Moreover, interleukin 1 (IL-1) is a major factor controlling the inflammatory response. The IL-1 gene family includes the IL-1α, IL-1β and the IL-1 receptor antagonist (IL-1Ra) genes that mediate immune and inflammatory responses. SNPs in IL-1α, IL-1β and IL1Ra modify bone mineral density promoting intervertebral disc disease (IDD). The simultaneous carriage of the IL-1bT3954 and the IL-1Ra A1812 alleles significantly enhances the risk of low back pain (LBP) occurrence, the number of days with pain, and the number of days with limitations in daily activities due to pain. A recent study suggested that methylation status of a single CpG site in the IL6 promoter is related to IL6 messenger RNA levels and that lower methylation contributes to the risk of developing Rheumatoid Arthritis. The investigators will try to identify if it there is a correlation with success of the epiduroscopy approach in terms of freedom from pain with genic expression and cytokine dosage. Finally, the investifators will compare the cytokine gene expression and the DNA methylation status of IL6 promoter in patients with favorable outcome and in no responders, to study the role in gene expression. This study is addressed to detect if the genetic variability might be used in near future in clinical setting, to predict the success of epiduroscopy.
Description: the frequency of rs1800795 in the promoter of the IL6 geneMeasure: genetic outcome Time: 36 months
Description: other known variants related to inflammation in IL1β and IL6 lociMeasure: genomic outcome Time: 36 months
Description: IL-6, IL-1β, IL1Ra and INFγ serum concentration before, immediately post epiduroscopy and after 1 monthMeasure: inflammation outcome Time: 36 months
Description: IL-6, IL-1β, IL1Ra and INFγ gene expression in blood cells obtained before, immediately post epiduroscopy and after 1 monthMeasure: gene expression outcome Time: 36 months
Description: IL-6, IL-1β, IL1Ra and INFγ gene expression in biopsy tissue cellsMeasure: biopsy tissue outcome Time: 36 months
Description: the methylation of the promoter of IL6Measure: methylation outcome Time: 36 months
There is one SNP
Concerning DNA polymorphisms, it has been demonstrated, in many disease-state meta-analyses, that the IL6 variant rs1800795 affect gene transcription and influences the IL-6 levels.
the frequency of rs1800795 in the promoter of the IL6 gene.
Concerning DNA polymorphisms, it has been demonstrated, in many disease-state meta-analyses that the IL6 variant rs1800795 affect IL6 gene transcription and influences the IL-6 levels ensuring the statistical robustness of the associations.