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

细胞粘附分子L1家族（L1-CAMs）参与调节神经系统的多种功能，包括细胞粘附、轴突导向和突触可塑性。我们研究了参与密切同源的L1细胞粘附分子（CHL 1）对神经病理性疼痛大鼠备用神经损伤（SNI）模型。SNI诱导CHL 1在L4/5 DRG神经元中的表达，特别是在小尺寸损伤的神经元和卫星细胞中。在脊髓中，CHL 1-免疫反应性增加，在板层I-II的背角同侧的损伤。超微结构研究阐明了CHL 1在同侧背角初级传入纤维轴突中的定位。CHL 1免疫反应阳性细胞主要分布于轴突-轴突、轴突-背角神经元（树突、索马）和轴突-胶质细胞（星形胶质细胞和小胶质细胞）之间的粘附。慢性鞘内注射抗CHL 1胞外区抑制CHL 1粘附的实验性研究显著预防和逆转了SNI诱导的机械性异常性疼痛。因此，CHL 1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.