Low Affinity NGF Receptor (p75 Neurotrophin Receptor) Inhibit Sensory Nerve Growth in Human Degenerative Nucleus Pulposus Cells

Abstract

Introduction Degeneration of the lumbar intervertebral disc is a cause of low back pain. The pathological mechanism is thought to be sensory nerve ingrowth into the inner layers of the degenerated intervertebral disc. NGF is also important for mediating inflammatory pain from intervertebral discs via the high-affinity receptor, TrkA. Recent research has also revealed that the low-affinity NGF receptor, p75 neurotrophic receptor (p75NTR), plays an important role in inflammatory pain. In most DRG neurons, innervating rat intervertebral discs were positive for two types of NGF receptors. However, the participative two types of NGF receptors have not been clarified in human degenerative discs. To evaluate the axonal growth and induction of a painful neuropeptide, CGRP, using neutralize antibody and extracted medium from human degenerative disc cells in vitro. Materials and Methods The nucleus pulposus (NP) of human intervertebral discs were harvested from patients with discogenic low back pain. Extracted medium from human degenerative intervertebral discs and rat DRGs were cultured with TrkA or p75NTR neutralize antibody. We evaluated the promotion of axonal growth and CGRP induction of DRG neurons in extracted medium from the NP using immunocytochemistry. Results The average length of growing axons in the NP and positive control group with TrkA or p75NTR neutralize antibody were significantly longer than that in the control group ( p < 0.001). The average length of growing axons in the NP group and positive control group was significantly shortened after TrkA and p75NTR neutralize antibody treatment ( p < 0.001). The percentage of CGRP-immunoreactive cells with growing axons was significantly shorter than in the NP and positive control group compared with the control groups with p75NTR neutralize antibody ( p < 0.05). The expression of CGRP in all group with TrkA neutralize antibody was not decreased. Conclusion TrkA and p75NTR were associated with the growing axons in extracted medium from the NP of human intervertebral discs. p75NTR were associated with the percentage of CGRP-immunoreactive cells with growing axons more than TrkA. These in vitro results may suggest that p75NTR is related with discogenic low back pain. Disclosure of Interest None declared References Yamauchi K, Inoue G, Koshi T, et al. Nerve growth factor of cultured medium extracted from human degenerative nucleus pulposus promotes sensory nerve growth and induces substance p in vitro. Spine 2009;34(21):2263–2269 Sugiura A, Ohtori S, Yamashita M, et al. Effect of applying p75NTR saporin to a punctured intervertebral disc on calcitonin gene-related peptide expression in rat dorsal root ganglion neurons. J Orthop Sci 2010;15(3):407–413 Fukui Y, Ohtori S, Yamashita M, et al. Low affinity NGF receptor (p75 neurotrophin receptor) inhibitory antibody reduces pain behavior and CGRP expression in DRG in the mouse sciatic nerve crush model. J Orthop Res 2010;28(3):279–283