Structural Plastic Changes of Cortical Gray Matter Revealed by Voxel-Based Morphometry and Histological Analyses in a Monkey Model of Central Post-Stroke Pain
Structural Plastic Changes of Cortical Gray Matter Revealed by Voxel-Based Morphometry and Histological Analyses in a Monkey Model of Central Post-Stroke Pain
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DOI：
10.1093/cercor/bhab098
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发表时间：
2021-04-16
期刊：
影响因子：
3.7
通讯作者：
Higo, Noriyuki
中科院分区：
文献类型：
--
作者：
Nagasaka, Kazuaki;Nemoto, Kiyotaka;Higo, Noriyuki
中枢性脑卒中后疼痛（CPSP）是由脑卒中后躯体感觉通路损害引起的一种慢性疼痛。对CPSP患者的几项脑成像研究表明，这种情况下的病理生理机制是疼痛相关脑区的适应不良可塑性。然而，CPSP患者的脑成像所显示的局部可塑性变化的时间分布及其细胞基础尚不清楚。为了研究这些问题，我们进行了基于体素的形态测量（VBM），使用T1加权磁共振成像和免疫组织化学分析与我们建立的CPSP猴模型。从丘脑单侧腹后外侧核出血性病变后8周，猴子表现出显着的行为变化，被解释为反映异常性疼痛。目前的VBM结果显示，在几个星期后的病变疼痛相关领域的灰质体积减少。此外，免疫组织化学染色在同侧后岛叶皮质（ipsi-PIC）和次级体感皮质（ipsi-SII），其中灰质体积显着减少，观察到的VBM结果，显示了显着减少兴奋性和抑制性突触末梢相比，完整的猴子。我们的研究结果表明，神经元形态的渐进性变化，包括在同侧PIC/SII的突触丢失，参与了CPSP。
Central post-stroke pain (CPSP) is a chronic pain caused by stroke lesions of somatosensory pathways. Several brain imaging studies among patients with CPSP demonstrate that the pathophysiological mechanism underlying this condition is the maladaptive plasticity of pain-related brain regions. However, the temporal profile of the regional plastic changes, as suggested by brain imaging of CPSP patients, as well as their cellular basis, is unknown. To investigate these issues, we performed voxel-based morphometry (VBM) using T1-weighted magnetic resonance imaging and immunohistochemical analysis with our established CPSP monkey model. From 8 weeks after a hemorrhagic lesion to the unilateral ventral posterolateral nucleus of the thalamus, the monkeys exhibited significant behavioral changes that were interpreted as reflecting allodynia. The present VBM results revealed a decrease in gray matter volume in the pain-related areas after several weeks following the lesion. Furthermore, immunohistochemical staining in the ipsilesional posterior insular cortex (ipsi-PIC) and secondary somatosensory cortex (ipsi-SII), where the significant reduction in gray matter volume was observed in the VBM result, displayed a significant reduction in both excitatory and inhibitory synaptic terminals compared to intact monkeys. Our results suggest that progressive changes in neuronal morphology, including synaptic loss in the ipsi-PIC/SII, are involved in the CPSP.