Department of Radiology and Biomedical Imaging, Yale University School of Medicine, New Haven Connecticut, USA.
Department of Radiology and Rutgers Biomedical and Health Sciences-New Jersey Medical School, Newark New Jersey, USA.
J Neurotrauma. 2021 Dec;38(24):3393-3405. doi: 10.1089/neu.2021.0190.
Because the presence of pain impedes motor recovery in individuals with spinal cord injury (SCI), it is necessary to understand their supraspinal substrates in translational animal models. Using functional magnetic resonance imaging (fMRI) in a rat model of hemicontusion cervical SCI, supraspinal changes were mapped and correlated with sensorimotor behavioral outcomes. Female adult rats underwent sham or SCI using a 2.5 mm impactor and 150 kdyn force. SCI permanently impaired motor activity in only the ipsilesional forelimb along with thermal hyperalgesia at 5 and 6 weeks. Spinal MRI at 8 weeks after SCI showed ipsilateral T1 and T2 lesions with no discernable lesions across shams. fMRI mapping during electrical forepaw stimulation indicated SCI-induced sensorimotor reorganization with an expansion of the contralesional forelimb representation. Resting state fMRI-based functional connectivity density (FCD), a marker of regional neuronal hubs, increased or decreased across brain regions involved in nociception. FCD increases after SCI were in the primary and secondary somatosensory cortices (S1 and S2), anterior cingulate cortex (ACC), insula, and the pre-frontal cortex (PFC), and decreases were across the hippocampus, thalamus, hypothalamus, and amygdala in SCI. Resting state functional connectivity (RSFC) assessments from the FCD altered regions of interest indicated cortico-cortical RSFC increases and cortico-insular, cortico-thalamic, and cortico-hypothalamic RSFC decreases after SCI. Hippocampus, amygdala, and thalamus showed decreased RSFC with most cortical regions and between themselves except the hippocampus-amygdala network, which showed increased RSFC after SCI. Whereas select nociceptive region's intrinsic activity associated strongly with evoked pain behaviors after SCI (e.g., PFC, ACC, hippocampus, thalamus, hypothalamus, M1, and S1) other nociceptive regions had weaker associations (e.g., amygdala, insula, auditory cortex, S1, S1, S2, and M2), but differed significantly in their intrinsic activities between sham and SCI. The weaker associated nociceptive regions may possibly encode both the evoked and affective components of pain.
由于疼痛的存在会阻碍脊髓损伤（SCI）患者的运动康复，因此有必要在转化动物模型中了解其皮质下基质。在半横断颈 SCI 大鼠模型中使用功能磁共振成像（fMRI），绘制了皮质下变化并将其与感觉运动行为结果相关联。成年雌性大鼠接受假手术或 SCI，使用 2.5mm 冲击器和 150 kdyn 力。只有同侧前肢的运动活动在 SCI 后永久受损，并且在 5 周和 6 周时出现热痛觉过敏。在 SCI 后 8 周进行脊髓 MRI 显示同侧 T1 和 T2 病变，而假手术中没有明显的病变。电前爪刺激期间的 fMRI 图谱显示 SCI 引起的感觉运动重组，对侧前肢的代表区域扩大。基于静息状态 fMRI 的功能连接密度（FCD），即区域神经元枢纽的标志物，在涉及伤害感受的脑区增加或减少。SCI 后 FCD 增加的区域位于初级和次级体感皮层（S1 和 S2）、前扣带皮层（ACC）、岛叶和前额叶皮层（PFC），而减少的区域位于海马体、丘脑、下丘脑和杏仁核。来自 FCD 改变的感兴趣区域的静息状态功能连接（RSFC）评估表明，SCI 后皮质-皮质 RSFC 增加，皮质-岛叶、皮质-丘脑和皮质-下丘脑 RSFC 减少。海马体、杏仁核和丘脑显示出与大多数皮质区域以及彼此之间的 RSFC 减少，除了海马体-杏仁核网络在 SCI 后显示出增加的 RSFC。SCI 后，与诱发性疼痛行为密切相关的选择伤害感受区域的固有活动（例如，PFC、ACC、海马体、丘脑、下丘脑、M1 和 S1），而其他伤害感受区域的关联较弱（例如，杏仁核、岛叶、听觉皮层、S1、S1、S2 和 M2），但在假手术和 SCI 之间它们的固有活动存在显著差异。较弱相关的伤害感受区域可能有可能编码疼痛的诱发性和情感成分。
