INTRODUCTION: The relationship between disc cells, nerves, and pain is poorly understood. Neurotrophins (signaling molecules involved in nerve survival, differentiation, migration, and neurite outgrowth), are expressed in non‐neuronal tissues including the disc. We hypothesize that in vitro exposure of human disc cells to IL‐1 will elevate neurotrophin expression.
METHODS: Following Review Board approval, annulus cells were cultured in 3D in collagen sponges (Biomater. 27:371‐6, 2006). Cells, isolated from 3 Thompson grade IV discs and a grade III discs, were grown for 9 days in control (minimal essential medium supplemented with 20% FBS (controls) or treated media (102 pM IL‐1 beta added). mRNA was isolated and processed for Affymetrix microarray analysis. Data were normalized/corrected for false discovery rate. Statistics used unpaired student t‐test; p<0.05 as significant.
RESULTS: Gene expression levels in IL‐1 treated cells were compared control cells. IL‐1 exposure significantly increased expression of neutrotrophin 3 (2.5 fold increase, p=0.047), brain‐derived neurotrophic factor (BDNF) (6.7 fold increase, p=0.014), and neuropilin 2 (3.5 fold increase, p=0.017) compared to controls.
DISCUSSION: Data show that proinflammatory cytokines can significantly increase expression of neurotrophins. IL‐1 plays an important role in the pathogenesis of disc degeneration (Le Maitre, Arthr Res Ther 2005, 7:R732). Our findings expand those of Prumessur et al. on expression of neurotrophins (Arth Res Ther 2008,10:R99), and provide the first disc documentation of expression of neurotrophin 3 and neuropilin 2. We had previously shown the presence of BDNF (Arth Res Ther 2008,10:R82). This work has direct translational relevance because it addresses the primary clinical issue with disc degeneration (low back pain), and because it opens the possibility of novel analgesic therapies based on development of specific small‐molecular antagonists to neurotrophins.