Study of nociceptive transduction pathways derived from the lumbar spine.

以前，人们认为腰椎间盘是由背根神经节（DRG）神经元经椎神经节段性支配的。通过逆行示踪方法，我们明确了下椎间盘（L5-L6）主要由上（L1和L2） DRG神经元通过交感神经干支配。此外，我们研究了多种疼痛相关分子如P物质（SP）、降钙素基因相关肽（CGRP）、分离素B4 （IB4）、P2X_3受体的表达，并采用免疫染色与逆行示踪相结合的方法。我们发现，支配椎间盘的神经元中约有一半是SP和CGRP免疫反应（-ir），而支配椎间盘的DRG神经元中只有一小部分是IB4和p2xr阳性。这表明含有肽的DRG神经元占据了传递和调节来自椎间盘的伤害性信息的主要亚群。Bennett等人报道了大鼠皮肤和内脏初级感觉神经元中CGRP-ir和ib4结合神经元的比例不同。他们得出结论，内脏传入神经中CGRP-ir神经元的比例较高，而内脏传入神经中ib4结合神经元的比例低于皮肤传入神经。因此，就两种类型的DRG神经元的比例而言，腰椎间盘与内脏器官具有相似的神经分布。然而，在椎间盘传入神经中，1b4抑制神经元的比例明显低于皮肤和内脏传入神经。由于CGRP-ir和1b4结合神经元分别被认为是ngf和gdnf敏感神经元，我们假设腰椎间盘的伤害性信息主要由ngf敏感神经元传递和调节。

Previously, it was believed that the lumbar intervertebral disc was innervated segmentally by dorsal root ganglion (DRG) neurons via the sinuvertebral nerves. Using retrograde tracing methods, we clarified 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 substance P (SP), calcitonin gene-related peptide (CGRP), isolectin B4 (IB4), P2X_3 receptor and using a combination of immunostaining with the retrograde tracing method We found that about half of the neurons innervating the disc were SP-and CGRP-immunoreactive (-ir), whilst, only a small proportion of the DRG neurons innervating the disc were IB4-and P2Xrpositive, indicating that peptidecontaining DRG neurons ate the main subpopulation which transmits and modulates nociceptive information from the disc.Bennett et al. reported that the proportions of CGRP-ir and IB4-binding neurons are different among cutaneous and visceral primary sensory neurons in the rat. They concluded that the proportion of CGRP-ir neurons was higher in visceral afferents, and the proportion of the IB4-binding neurons was lower in visceral afferents than in cutaneous afferents. Thus, the lumbar intervertebral disc had similar neural profiles to that of visceral organs with regard to the proparions of the two types of DRG neurons. However, the proportion of 1B4-biding neurons is dramatically lower in the disc afferents than cutaneous and visceral afferents. Since CGRP-ir and 1B4-binding neurons are thought to be NGF-and GDNF-sensitive neurons respectively, we suppose that nociceptive information from the lumbar intervertebral disc is mainly transmitted and modulated by NGF-sensitive neurons.