Cytokine evaluation in individuals with low back pain using discographic lavage

Abstract 

Background context

The pathophysiology underlying degenerative disc disease and its implication in painful syndromes remain unclear. However, spine magnetic resonance imaging (MRI) can demonstrate changes in disc water content and the annulus; provocative discography purportedly identifies degenerate discs causing serious low back pain; and biochemical assays have identified local inflammatory markers. No study to date has correlated pain on disc injection during discography evaluation with relevant MRI findings and biochemical markers.

Purpose

The purpose of this study was to correlate concordant pain on during discography to biochemical markers obtained by disc lavage and MRI findings.

Study design

This is a Phase 1 Diagnostic Test Assessment Cohort Study (Sackett and Haynes).

Patient sample

The patient sample included 21 symptomatic patients with suspected discogenic pain and three Phase 1 control subjects.

Outcome measures

The outcome measures included discography pain scores, MRI degenerative grades, and immunoreactivity to various inflammatory cytokine concentrations present in disc lavage samples.

Methods

Twenty-one symptomatic patients with lumbar degenerative disc disease and three control subjects underwent discography, MRI, and biochemical analysis of disc lavage fluid. Lumbar MRI was scored for Pfirrmann grading of the lumbar discs, and annular disruption was identified by nuclear disc lavage. Disc lavage samples were analyzed for biochemical markers by high-sensitivity immunoassay.

Results

Eighty-three discs from 24 patients were studied: 67 discs from 21 patients with axial back pain (suspected discogenic pain group) and 16 discs from 3 scoliosis patients without back pain (Phase 1 control subjects). Among the biochemical markers surveyed, interferon gamma (IFN-γ) immunoreactivity was most consistently identified in patients with axial back pain. Discs with annular disruption and concordant pain reproduction at a visual analog scale of 7 to 10/10 had greater IFN-γ immunoreactivity than those without this finding (p=.003); however, at least some IFN-γ immunoreactivity was found in all but one disc in the symptomatic group.

Conclusions

Among the potential inflammatory markers tested in this Phase 1 study, IFN-γ immunoreactivity was most commonly elevated in discogram “positive” discs but absent in asymptomatic controls. However, this marker was also frequently elevated in degenerative but “negative” discography discs. From these findings, Phase 2 and Phase 3 validity studies are reasonable to pursue. Phase 4 utility studies may be performed concurrently to assess this method's predictive value in outcome studies.

Keywords: Intervertebral disc, Cytokines, Interferon gamma, Discography, Low back pain