Maguire Aislinn D, Bethea John R, Kerr Bradley J
Neuroscience and Mental Health Institute, University of Alberta, Edmonton, AB, Canada.
Drexel University, Philadelphia, PA, United States.
Front Neurol. 2021 Dec 6;12:780876. doi: 10.3389/fneur.2021.780876. eCollection 2021.
Multiple Sclerosis (MS) is a debilitating autoimmune disease often accompanied by severe chronic pain. The most common type of pain in MS, called neuropathic pain, arises from disease processes affecting the peripheral and central nervous systems. It is incredibly difficult to study these processes in patients, so animal models such as experimental autoimmune encephalomyelitis (EAE) mice are used to dissect the complex mechanisms of neuropathic pain in MS. The pleiotropic cytokine tumor necrosis factor α (TNFα) is a critical factor mediating neuropathic pain identified by these animal studies. The TNF signaling pathway is complex, and can lead to cell death, inflammation, or survival. In complex diseases such as MS, signaling through the TNFR1 receptor tends to be pro-inflammation and death, whereas signaling through the TNFR2 receptor is pro-homeostatic. However, most TNFα-targeted therapies indiscriminately block both arms of the pathway, and thus are not therapeutic in MS. This review explores pain in MS, inflammatory TNF signaling, the link between the two, and how it could be exploited to develop more effective TNFα-targeting pain therapies.
多发性硬化症（MS）是一种使人衰弱的自身免疫性疾病，常伴有严重的慢性疼痛。MS中最常见的疼痛类型称为神经性疼痛，它源于影响外周和中枢神经系统的疾病进程。在患者中研究这些进程极其困难，因此诸如实验性自身免疫性脑脊髓炎（EAE）小鼠等动物模型被用于剖析MS中神经性疼痛的复杂机制。多效性细胞因子肿瘤坏死因子α（TNFα）是这些动物研究确定的介导神经性疼痛的关键因子。TNF信号通路很复杂，可导致细胞死亡、炎症或存活。在诸如MS等复杂疾病中，通过TNFR1受体的信号传导往往是促炎和促死亡的，而通过TNFR2受体的信号传导则是促稳态的。然而，大多数针对TNFα的疗法会不加区分地阻断该通路的两个分支，因此在MS中并无治疗效果。本综述探讨了MS中的疼痛、炎性TNF信号传导、两者之间的联系，以及如何利用这种联系开发更有效的靶向TNFα的疼痛疗法。
