A cell adhesion molecule close homologue of L1 increased in primary afferent terminal contributes to the development and maintenance of neuropathic pain

已知细胞粘附分子L1家族（L1- cams）调节各种神经系统的关键神经功能，包括细胞粘附、轴突引导和突触可塑性。我们研究了L1细胞粘附分子（CHL1）的密切同源物在大鼠免于神经损伤（SNI）模型中产生的神经性疼痛中的作用。SNI诱导了L4/5 DRG神经元中CHL1的表达，特别是在小尺寸损伤神经元和卫星细胞中。在脊髓中，损伤同侧背角I-II椎板的chl1免疫反应性增加。超微结构研究明确了CHL1在同侧背角初级传入神经轴突的定位。CHL1的免疫反应局限于粘附细胞，如轴突-轴突、轴突-背角神经元（树突、体细胞）和轴突胶质细胞（星形胶质细胞和小胶质细胞）。慢性鞘内给药抗CHL1细胞外结构域对CHL1粘附的实验性抑制显著阻止了逆转sni诱导的机械异常性痛。因此，CHL1的改变可能涉及与神经性疼痛相关的结构可塑性。

The L1 family of cell adhesion molecules (L1-CAMs) is known to regulate various neural functions that are pivotal to nervous system, including cell adhesion, axon guidance and synaptic plasticity. We investigated the involvement of a close homologue of the L1 cell adhesion molecule (CHL1) on neuropathic pain produced in the rat spared nerve injury (SNI) model. SNI induced the expression of CHL1 in L4/5 DRG neurons, particularly in small size injured neurons and in satellite cells. In the spinal cord, CHL1-immunoreactivity increased in laminae I-II of the dorsal horn ipsilateral to the injury. Ultrastructural study clarified the localization of CHL1 in the axon of primary afferents in the ipsilateral dorsal horn. CHL1 immunoreactivites were localized in the adherence such as axon- axon, axon-dorsal horn neurons (dendrite, soma) and axon-glia (astrocyte and microglia). Experimental inhibition of CHL1 adhesion by chronic intrathecal administration of the anti-CHL1 extracellular domain significantly prevented andreversed SNI-induced mechanical allodynia. Thus, alterations of CHL1 may be involved in the structural plasticity that is associated with neuropathic pain.