General Session: Innovative Technologies I - Hall F

Presented by: O.N. Hausmann

Author(s):

A. Sadowska(1), E. Touli(2), W. Hitzl(3), H. Greutert(1), S.J. Ferguson(1), K. Wuertz-Kozak(1,4),(5), O.N. Hausmann(2)

(1) ETH, Department of Health Sciences and Technology, Zurich, Switzerland
(2) Klinik St. Anna-Hirslanden, Neuro- and Spine Center, Lucerne, Switzerland
(3) Research Office (Biostatistics) , Paracelsus Medical University, Salzburg, Austria
(4) Schön Clinic Munich Harlaching, Spine Center, Munich, Germany
(5) University of Potsdam, Department of Health Sciences, Potsdam, Germany

Abstract

Introduction: Disc degeneration (DD) is an age-related process that occurs early in life and is associated with low back pain with approximately ~80% of the population suffering from it at some point in their lifetime. Certain individuals experience age-related chronic inflammation of the intervertebral disc (IVD), termed "inflammaging", which is characterized by up-regulation of proinflammatory cytokines such as interleukin-6 (IL-6). Due to their putative role in pain-transduction and inflammation, Transient Receptor Potential (TRP) channels may contribute to DD and discogenic pain and hence be of mechanistic relevance in disc inflammaging. The aim of this study was to investigate and compare the occurrence of inflammatory processes in the sites of disc degeneration in the lumbar and cervical spine and to investigate the mechanistic involvement of Transient Receptor Potential Channels TRPC6 and TRPV4.

Methods: A total of 51 disc samples were obtained after informed consent from 45 patients (18 men, 27 women, mean age=52) undergoing elective spinal surgery in the cervical (n=24) or lumbar (n=21) region. The procedures were approved by the local ethical committee. Gene expression of inflammatory cytokines and TRP channels was analyzed for differences with regard to spinal level (lumbar vs cervical), pathology (disc herniation (DH) vs DD), Pfirrmann degeneration grade, Modic grade, age, sex, disc region (annulus fibrosus (AF) vs nucleus pulposus (NP)) and surgical extent. For statistical analysis, the Wilcoxon-matched pairs test, Mann-Whitney U test and Spearman correlation were used. All reported tests were two-sided, and p-values < 0.05 were considered as statistically significant.

Results: Aside from genes with known implication in DD and DH, four previously unreported genes from the interferon and TRP families (IFNA1, IFNA8, IFNB1, TRPC6) could be detected. A correlation between gene expression and age (IL-15) as well as degeneration grade (IFNA1, IL-6, IL-15, TRPC6), but not Modic grade, was identified. Significant differences were detected between cervical and lumbar discs (IL-15, Figure 1a), NP and AF (IL-6, TNF-α, TRPC6), single-level and multi-level surgery (IL-6, IL-8) as well as DD and DH (IL-8), while sex had no effect. Multiple gene-gene pair correlations, either between different cytokines or importantly also between cytokines and TRP channels (Figure 1b), exist in the disc.

Conclusion: Our study unveiled a potentially crucial role of Ca2+ permeable cation channels, specifically of TRPC6, in the disc inflammaging. Furthermore, we confirmed the presence of the pro-inflammatory cytokines IL-1B, TNF-α, IL-6 and IL-8 in degenerative disc disease and highlighted the expression and relevance of cytokines that have previously gained little or no attention in disc research (INFA1, IFNA8, INFB1, IL-15). Importantly, we were able to demonstrate that the expression of IL-15, INFA1, IL-6, IL-8 and TRPC6 was affected by central patient/tissue characteristics, such as the degeneration grade, age, spinal level and/or pathology. These molecules may hence constitute targets to modulate the process of disc degeneration and pain development.

Figure 1