Olechowski Camille J, Truong Janet J, Kerr Bradley J
Centre for Neuroscience, University of Alberta, Edmonton, Alta., Canada.
Pain. 2009 Jan;141(1-2):156-64. doi: 10.1016/j.pain.2008.11.002. Epub 2008 Dec 11.
Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system (CNS). While the primary symptoms of MS are losses of sensory and motor functions, it is now recognized that chronic pain is also a major concern affecting between 50% and 80% of MS patients. To date, however, few studies have examined the underlying mechanisms of chronic pain in MS or in the animal model, experimental autoimmune encephalomyelitis (EAE), which shares many features of MS pathology. We, therefore, set out to characterize the changes in pain sensitivity that arises in a chronic-relapsing model of EAE. We show here that female C57BL/6 mice immunized with myelin oligodendrocyte glycoprotein (MOG(35-55)) develop a robust allodynia to both cold and tactile stimuli. Allodynia emerges early in the disease process, often before any signs of neurological deficit and is independent of the overall symptom severity in these mice. "Classical" cellular substrates for neuropathic pain and allodynia such as altered expression of sensory neuropeptides in the dorsal horn of the spinal do not appear to underlie these changes in sensory function. There is, however, a significant influx of CD3+ T cells and increased astrocyte and microglia/macrophage reactivity in the superficial dorsal horn of mice with MOG(35-55) EAE. This suggests that inflammation and reactive gliosis may be key mediators of allodynia in MOG(35-55) EAE similar to peripheral nerve and spinal cord injury models. Taken together, our results show that the MOG(35-55) EAE model is a useful tool to study neuropathic pain in MS.
多发性硬化症(MS)是一种中枢神经系统(CNS)的炎性脱髓鞘疾病。虽然MS的主要症状是感觉和运动功能丧失,但现在人们认识到慢性疼痛也是一个主要问题,影响着50%至80%的MS患者。然而,迄今为止,很少有研究探讨MS或实验性自身免疫性脑脊髓炎(EAE)动物模型中慢性疼痛的潜在机制,EAE与MS病理学有许多共同特征。因此,我们着手描述EAE慢性复发模型中出现的疼痛敏感性变化。我们在此表明,用髓鞘少突胶质细胞糖蛋白(MOG(35-55))免疫的雌性C57BL/6小鼠对冷刺激和触觉刺激均出现强烈的异常性疼痛。异常性疼痛在疾病过程早期出现,通常在任何神经功能缺损迹象之前,且与这些小鼠的总体症状严重程度无关。“经典”的神经性疼痛和异常性疼痛的细胞底物,如脊髓背角感觉神经肽表达改变,似乎不是这些感觉功能变化的基础。然而,在患有MOG(35-55) EAE的小鼠的浅表背角中,有大量CD3+ T细胞流入,星形胶质细胞和小胶质细胞/巨噬细胞反应性增加。这表明炎症和反应性胶质增生可能是MOG(35-55) EAE中异常性疼痛的关键介质,类似于周围神经和脊髓损伤模型。综上所述,我们的结果表明,MOG(35-55) EAE模型是研究MS中神经性疼痛的有用工具。