Modic changes are associated with increased disc inflammatory mediator production

Abstract

John Burke, FRCSI, Little Benton, Newcastle, United Kingdom; R.William Watson, PhD, D. McCormack, MCh, John M. Fitzpatrick, FRCSI, J. Slack, Martin G. Walsh, FRCSI, Dublin, IrelandBackground context: Modic changes have an inflammatory appearance. There have been a number of reports in the literature linking Modic changes with discogenic pain. Much work has been done investigating the role of disc pro-inflammatory mediator production by herniated degenerate discs. To date, there has been no biochemical investigation of discs with associated Modic changes.Purpose: The aim of this study is to determine if degenerate discs with associated Modic changes have higher levels of pro-inflammatory mediator production than those without Modic changes.Materials and methods: Intervertebral disc tissue was obtained from 52 patients undergoing spinal surgery for sciatica (40) and discogram-proven discogenic low back pain (12). The tissue was cultured and the medium analyzed for interleukin-6 (IL-6), interleukin-8 (IL-8) and prostaglandin E2 (PGE2) using an enzyme-linked immunoabsorbent assay method. Preoperative magnetic resonance images of the patients were examined by a double-blinded radiologist to determine the Modic status of the cultured disc level.Results: There was a statistically significant difference between levels of IL-6, IL-8 and PGE2 production by both the Modic 1 (M1) and Modic 2 (M2) groups compared with the Modic negative (NEG) group. IL-6: NEG versus M1 p<.001, NEG versus M2 p<.05. IL-8: NEG versus M1 p<.01, NEG versus M2 p<.05. PGE2: NEG versus M1 p<.01, NEG versus M2 p<.05. Forty percent of patients undergoing surgery for discogenic low back pain had a Modic 1 change compared with only 12.5% of patients undergoing surgery for sciatica (p<.05).Conclusions: The incidence of Modic changes is much greater in the symptomatic disc population than in the degenerate disc population as a whole. Modic reported that 4% of degenerate discs had an associated Modic 1 change and 15% of degenerate discs have an associated Modic 2 change. In the symptomatic degenerate disc population examined here, the overall incidence of Modic changes is 60%. This breaks down into 20% Modic 1 and over 40% Modic 2. This strongly suggests that Modic changes have clinical significance and are not just an incidental finding. Modic 1 changes are more common in patients with discogenic low back pain, whereas Modic 2 changes occur in 50% of patients who have surgery for sciatica. The ability of Modic positive discs to be symptomatic is supported by their high levels of inflammatory mediator production. Modic changes have been associated with a positive discogram by a number of authors. IL-8 and PGE2 are known to induce hyperalgesia. The fact that Modic changes are associated with high levels of production of these mediators supports their role as an objective marker of discogenic low back pain.