三叉神经痛琼脂压迫模型的中枢和外周结构研究*

Study of central and peripheral structures in an agar compression model of trigeminal neuralgia

摘要:

目的：通过3D定位建立琼脂压迫动物模型模拟三叉神经痛（trigeminal neuralgia, TN），利用影像学扫描进行模型验证，并通过采集不同模型的行为学、影像学及病理学等相关数据，对模型进行分析，以便于进一步探索TN的发病机制。方法：用von Frey测痛纤维丝筛选出痛阈值在8~15 g的SD大鼠32只，建立琼脂压迫三叉神经根模型，术后1~7周通过von Frey测痛纤维丝测定大鼠机械性疼痛阈值，术后4周、8周、12周进行灰质体积的基于体素的形态学分析（value based management, VBM），采集术后8周和12周的三叉神经颅内段（intracranial segment, ICS）和眶下段神经 (infraorbital nerve, ION )神经利用透射电镜（transmission electron microscope, TEM）进行超微结构分析。结果：机械痛阈值结果：琼脂实验组术后机械刺激阈值出现降低，可持续至术后42天，琼脂对照组在术后14天内有轻度机械刺激阈值降低。TEM结果：实验组于术后8周和12周的三叉神经ICS和ION的电镜结果均观察到明显脱髓鞘改变，且术后12周较术后8周更严重。灰质体积VBM分析：琼脂组大鼠术后4周脑灰质体积未出现明显变化。8周时左侧旁下托、左侧齿状回、左侧胼胝体压部、右侧顶叶联合皮质、下丘脑、右侧基底前脑、右侧纹状体及双侧初级躯体感觉皮层灰质体积显著减少。12周时这些变化范围明显扩大，甚至蔓延到双侧脑区；另外新观察到导水管周围灰质、左侧内嗅皮层、双侧扣带回及双侧海马的灰质体积显著减少。全脑分析显示各脑区没有灰质体积增加。结论：1.琼脂压迫模型能产生稳定且较长持续时间疼痛，可作为继发性TN的可靠模型用于对TN发病机制、治疗等进一步研究。2.ICS段神经损伤可经神经扩散或通过神经周围传导从而累及三叉神经ION段。3.短期内（8周至12周），随时间延长，TN神经脱髓鞘损伤呈加重趋势。4.琼脂压迫模型的头颅VBM分析与TN患者较为符合。

Abstract:

Establish an agar compressed animal model through 3D localization to simulate trigeminal neuralgia (TN), validate the model using imaging scans, and analyze the model by collecting behavioral, imaging, and pathological data from different models, in order to further explore the pathogenesis of TN. Methods: 32 SD rats with a pain threshold of 8-15 g were selected using von Frey's pain measuring filaments to establish an agar compressed trigeminal nerve root model. The mechanical pain threshold of the rats was measured using von Frey's pain measuring filaments at 1-7 weeks postoperatively. Value based management (VBM) of gray matter volume was performed at 4, 8, and 12 weeks postoperatively, Collect intracranial segment (ICS) and infraorbital nerve (ION) nerves of the trigeminal nerve at 8 and 12 weeks after surgery for ultrastructural analysis using transmission electron microscopy (TEM). Results: Mechanical pain threshold Results: The mechanical stimulation threshold in the agar experimental group decreased after surgery, lasting until 42 days after surgery. The mechanical stimulation threshold in the agar control group decreased slightly within 14 days after surgery. TEM results: In the experimental group, significant demyelinating changes were observed in both the trigeminal nerve ICS and ION electron microscopic results at 8 and 12 weeks after surgery, and the 12 weeks after surgery were more severe than the 8 weeks after surgery. VBM analysis of gray matter volume: There was no significant change in the brain gray matter volume of the rats in the agar group 4 W after surgery. At 8 weeks, the volume of gray matter in the left lateral inferior fossa, left dentate gyrus, left corpus callosum, right parietal cortex, hypothalamus, right basal forebrain, right striatum, and bilateral primary somatosensory cortex decreased significantly. At 12 weeks, these changes significantly expanded and even spread to bilateral brain regions; In addition, it was newly observed that the volume of gray matter in the periaqueductal gray matter, the left entorhinal cortex, the bilateral cingulate gyrus, and the bilateral hippocampus decreased significantly. Whole brain analysis showed no increase in gray matter volume in each brain region. Conclusion: 1. The agar compression model can produce stable and long-lasting pain, and can be used as a reliable model for further research on the pathogenesis and treatment of TN. 2. Nerve injury in the central ICS segment can involve the trigeminal ION segment through nerve diffusion or peripheral conduction. 3. In the short term (8 W to 12 W), the demyelinating injury of the TN nerve tends to worsen with time. 4. The VBM analysis of the head of the agar compression model was more consistent with TN patients.