Aoki Yasuchika, Takahashi Yuzuru, Ohtori Seiji, Moriya Hideshige, Takahashi Kazuhisa
Department of Orthopedic Surgery, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo, Chiba, 260-8670, Japan.
Life Sci. 2004 Apr 9;74(21):2627-42. doi: 10.1016/j.lfs.2004.01.008.
Previously, it was believed that the lumbar intervertebral disc was innervated segmentally by dorsal root ganglion (DRG) neurons via the sinuvertebral nerves. Recently, it was demonstrated using retrograde tracing methods that the lower disc (L5-L6) is innervated predominantly by upper (L1 and L2) DRG neurons via the sympathetic trunks. Furthermore, we investigated the expression of various pain-related molecules such as calcitonin gene-related peptide (CGRP), isolectin B4 (IB4), P2X(3) receptor and vanniloid receptor 1 (VR1) in DRG neurons innervating the disc using a combination of immunostaining with the retrograde tracing method. This review outlines the distribution and immunocytochemical characterization of DRG neurons innervating the disc. Small nociceptive DRG neurons are classified into nerve growth factor (NGF)-dependent neurons and glial cell line-derived neurotrophic factor (GDNF)-dependent neurons and they can be distinguished by their reactivity for CGRP and IB4, respectively. We found that about half of the neurons innervating the disc were CGRP-immunoreactive (-ir), whilst, only 0.6% of the DRG neurons were IB4-positive, thereby indicating that NGF-dependent neurons are the main subpopulation which transmits and modulates nociceptive information from the disc. In addition, we also demonstrated P2X(3)- and VR1-immunoreactivity in DRG neurons innervating the disc and noted that they were mainly localized in NGF-dependent neurons. It is well known that NGF has sensitizing effects on DRG neurons, with a recent study demonstratng the presence of NGF in the painful intervertebral disc. Therefore, it is suggested that NGF is involved in the generation of discogenic low back pain.
以前，人们认为腰间盘由背根神经节（DRG）神经元经窦椎神经进行节段性神经支配。最近，通过逆行追踪方法证明，下部椎间盘（L5-L6）主要由上部（L1和L2）DRG神经元经交感干进行神经支配。此外，我们使用免疫染色与逆行追踪方法相结合，研究了支配椎间盘的DRG神经元中各种疼痛相关分子的表达，如降钙素基因相关肽（CGRP）、异凝集素B4（IB4）、P2X（3）受体和香草酸受体1（VR1）。本综述概述了支配椎间盘的DRG神经元的分布和免疫细胞化学特征。小型伤害性DRG神经元分为神经生长因子（NGF）依赖性神经元和胶质细胞系衍生的神经营养因子（GDNF）依赖性神经元，它们可分别通过对CGRP和IB4的反应性来区分。我们发现，支配椎间盘的神经元中约一半是CGRP免疫反应性（-ir）的，而DRG神经元中只有0.6%是IB4阳性的，从而表明NGF依赖性神经元是传递和调节来自椎间盘伤害性信息的主要亚群。此外，我们还证明了支配椎间盘的DRG神经元中存在P2X（3）和VR1免疫反应性，并指出它们主要定位于NGF依赖性神经元中。众所周知，NGF对DRG神经元有敏化作用，最近的一项研究表明疼痛的椎间盘中存在NGF。因此，提示NGF参与了椎间盘源性下腰痛的发生。
