1074 Inhibition of CSF1R Pathway Alleviates Discogenic Back Pain and Slows Down Intervertebral Disc Degeneration

INTRODUCTION: Intervertebral disc (IVD) degeneration is one of the major causes of low back pain. Inflammation has been implicated in discogenic back pain and disc degeneration, however, the detailed molecular mechanisms remain unclear. METHODS: To study the role of inflammatory cell CSF1R signaling in neuropathic pain after disc injury, we employed a strategy to specifically delete CSF1R in CX3CR1+ cells by crossing CX3CR1CreER mice with CSF1Rfl/fl mice (CX3CR1CreER/+:CSF1Rfl/fl) and subsequently induced expression of cre recombinase via tamoxifen (TAM) injection. To create a robust and reproducible model of IVD degeneration and discogenic back pain, we modified an existing IVD puncture procedure. The lumbar spine was approached via posterolateral angle on the right side. The L4/5 and L5/6 IVD was accessed/punctured through minimal paraspinal muscle using a 25G custom-made needle. RESULTS: Disc injury induces CSF1 de novo production in DRGs and transport to the dorsal horn of spinal cord. Genetic deletion of CSF1R from microglia/macrophages or oral administration of a CSF1R competitive inhibitor, GW2580, inhibited pro-inflammatory cytokine release from injured discs and blocked dorsal root ganglion (DRG) macrophage and spinal cord dorsal horn microglia activation and in so doing, eliminated neuropathic pain secondary to disc injury. CSF1R deletion or GW2580 administration also decreased IVD degeneration as evidenced by serial magnetic resonance imaging (MRI) and histopathological analyses in adult mice following disc injury. CONCLUSIONS: Colony Stimulating Factor 1 Receptor (CSF1R) signaling plays an essential role in the development of IVD degeneration and discogenic back pain. These results suggest a novel therapeutic strategy for the treatment of chronic low back pain secondary to IVD degeneration.