Heterogeneous macrophages contribute to the pathology of disc herniation induced radiculopathy.
Heterogeneous macrophages contribute to the pathology of disc herniation induced radiculopathy.
复制标题
异质巨噬细胞导致椎间盘突出引起的神经根病的病理学。
DOI：
10.1016/j.spinee.2021.10.014
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发表时间：
2022-04
期刊：
影响因子：
--
通讯作者：
Li XJ
中科院分区：
文献类型：
--
作者：
Jin L;Xiao L;Ding M;Pan A;Balian G;Sung SJ;Li XJ
巨噬细胞在椎间盘突出症和神经根病的进展中起重要作用。为了更好地了解巨噬细胞在这一过程中的作用，我们开发了一种新的模拟人类神经根病的小鼠模型。临床前随机动物研究。在随机分配的Balb/c小鼠中进行三种类型的手术。这些是脊神经暴露、传统前椎间盘穿刺和外侧椎间盘穿刺伴神经暴露（n=16/组）。对于神经暴露组，暴露左侧L5脊神经而不损伤椎间盘。对于传统的前路穿刺，按照先前建立的方法，通过前路穿刺L5/6椎间盘。对于神经暴露的侧向穿刺，通过去除腰大肌肌纤维暴露左侧L5脊神经，并且用30 G针在左侧侧向穿刺L5/6椎间盘，使核朝向L5脊神经突出。后爪的机械性痛觉过敏（疼痛敏感性）用电子von Frey测定在交替的一天进行评估，持续长达2周。进行MRI、组织学和免疫染色以确认椎间盘突出和炎症。侧刺神经暴露组的同侧疼痛明显大于其他组。术后第7天，两组穿刺组疝点及侧穿刺不暴露组脊神经处促炎细胞因子IL-1β、IL-6均明显升高。在该小鼠模型的浸润组织中和接受椎间盘切除术的患者的组织中检测到巨噬细胞的异质群体。我们建立了一个新的小鼠模型，模拟人类神经根病，并证明了巨噬细胞的混合表型有助于急性椎间盘源性神经根病的发病机制。本研究提供了一个临床相关的体内动物模型，以阐明椎间盘突出和神经根性疼痛的复杂相互作用，这可能为开发巨噬细胞锚定疗法来治疗神经根病提供了机会。
Macrophages play important roles in the progression of intervertebral disc herniation and radiculopathy. To better understand the roles of macrophages in this process, we developed a new mouse model that mimics human radiculopathy. A preclinical randomized animal study. Three types of surgeries were performed in randomly assigned Balb/c mice. These were spinal nerve exposure, traditional anterior disc puncture, and lateral disc puncture with nerve exposure (n=16/group). For the nerve exposure group, the left L5 spinal nerve was exposed without disc injury. For the traditional anterior puncture, L5/6 disc was punctured by an anterior approach as previously established. For lateral puncture with nerve exposure, the left L5 spinal nerve was exposed by removing the psoas major muscle fibers, and the L5/6 disc was punctured laterally on the left side with a 30G needle, allowing the nucleus to protrude toward the L5 spinal nerve. Mechanical hyperalgesia (pain sensitivity) of hind paws was assessed with electronic von Frey assay on alternative day for up to 2 weeks. MRI, histology, and immunostaining were performed to confirm disc herniation and inflammation. Ipsilateral pain in the lateral puncture with nerve exposure group was significantly greater than the other groups. Pro-inflammatory cytokines IL-1β and IL-6 were markedly elevated at the hernia sites of both puncture groups and the spinal nerve of lateral puncture with never exposure group on postoperative day 7. Heterogeneous populations of macrophages were detected in the infiltration tissue of this mouse model and in tissue from patients undergone discectomy. We have established a new mouse model that mimics human radiculopathy and demonstrates that a mixed phenotype of macrophages contribute to the pathogenesis of acute discogenic radiculopathy. This study provides a clinically relevant in vivo animal model to elucidate complex interactions of disc herniation and radicular pain, which may present opportunities for the development of macrophage-anchored therapeutics to manage radiculopathy.
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