Peripheral and central neuroinflammatory changes and Pain Behaviors in an animal Model of Multiple sclerosis
Peripheral and central neuroinflammatory changes and Pain Behaviors in an animal Model of Multiple sclerosis
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DOI：
10.3389/fimmu.2016.00369
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发表时间：
2016-09-22
影响因子：
7.3
通讯作者：
Moalem-Taylor, Gila
中科院分区：
文献类型：
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作者：
Duffy, Samuel S.;Perera, Chamini J.;Moalem-Taylor, Gila
疼痛是多发性硬化症 (MS) 的一种广泛且令人衰弱的症状，多发性硬化症是一种中枢神经系统的慢性炎症性脱髓鞘疾病。尽管中枢神经炎症和脱髓鞘与多发性硬化症相关疼痛有关，但外周和中枢机制在疾病不同阶段的作用仍不清楚。在这项研究中，我们使用实验性自身免疫性脑脊髓炎（EAE）动物模型来检查慢性疾病过程中刺激诱发和自发的疼痛行为以及神经炎症变化。我们发现后爪的机械异常性疼痛先于临床 EAE 发作，但在临床高峰时无法测量。这种机械超敏反应与脊髓背角小胶质细胞激活的增加同时发生。面部机械异常性疼痛的发生也出现在临床前 EAE 中，持续在临床高峰期，并且与周围三叉神经传入通路的病理学相对应。这包括 T 细胞浸润，这种浸润发生在明显的中枢病变形成之前，以及临床高峰期对有髓神经元的特定损伤之前。使用小鼠鬼脸量表（一种基于面部表情的编码系统）测量自发疼痛，结果显示患有 EAE 的小鼠在临床疾病期间面部鬼脸增多。这与多种外周和中枢神经炎症变化相关，包括髓鞘少突胶质细胞减少、T 细胞浸润增加以及巨噬细胞/小胶质细胞和星形胶质细胞激活。总的来说，这些发现表明不同的病理机制可能是 EAE 中刺激诱发和自发疼痛的基础，并且这些行为在疾病的独特阶段占主导地位。
Pain is a widespread and debilitating symptom of multiple sclerosis (MS), a chronic inflammatory demyelinating disease of the central nervous system. Although central neuroinflammation and demyelination have been implicated in MS-related pain, the contribution of peripheral and central mechanisms during different phases of the disease remains unclear. In this study, we used the animal model experimental autoimmune encephalomyelitis (EAE) to examine both stimulus-evoked and spontaneous pain behaviors, and neuroinflammatory changes, over the course of chronic disease. We found that mechanical allodynia of the hind paw preceded the onset of clinical EAE but was unmeasurable at clinical peak. This mechanical hypersensitivity coincided with increased microglial activation confined to the dorsal horn of the spinal cord. The development of facial mechanical allodynia also emerged in preclinical EAE, persisted at the clinical peak, and corresponded with pathology of the peripheral trigeminal afferent pathway. This included T cell infiltration, which arose prior to overt central lesion formation and specific damage to myelinated neurons during the clinical peak. Measurement of spontaneous pain using the mouse grimace scale, a facial expression-based coding system, showed increased facial grimacing in mice with EAE during clinical disease. This was associated with multiple peripheral and central neuroinflammatory changes including a decrease in myelinating oligodendrocytes, increased T cell infiltration, and macrophage/microglia and astrocyte activation. Overall, these findings suggest that different pathological mechanisms may underlie stimulus-evoked and spontaneous pain in EAE, and that these behaviors predominate in unique stages of the disease.