Laboratoire de Neurobiologie, CNRS UMR 7637, Ecole Supérieure de Physique et de Chimie Industrielles, 10 rue Vauquelin, 75005 Paris, France.
Eur J Pain. 2011 Mar;15(3):231.e1-16. doi: 10.1016/j.ejpain.2010.07.010. Epub 2010 Sep 9.
Multiple sclerosis is a chronic inflammatory demyelinating disease, associated, in 50-80% of patients, with persistent pain. While the type of pain that affects these patients is being more documented, the mechanisms underlying this pathology are still poorly understood and animal models of such chronic pain associated with MS are required. The aim of our study was to characterize the sensory abnormalities and in particular the clinical signs linked to persistent pain in two models of Experimental Autoimmune Encephalomyelitis (EAE) in the rat. This behavioural characterization tested several sensory modalities such as mechanical and thermal (heat/cold) hyperalgesia or allodynia and explored some of these modalities on two different extremities: the hindpaws and the tail. Our study showed that while one of the model produced more robust motor impairment, animals of both models suffer from mechanical hyperalgesia and thermal allodynia to cold, both at the level of the tail and the hindpaws. While the time-course changes of some of these modalities are shifted in the time between the two models, they represent good models of the sensory abnormalities experienced by MS patients. The second part of our study aimed at characterizing from a pharmacological point of view the most robust model ("EAE+Cyclosporine") and showed that Gabapentin, Duloxetine and Tramadol partially relieved some of the clinical signs. Our results suggest that the model "EAE+Cyclosporine" in the rat is a good model of chronic sensory abnormalities observed in MS patients both from a behavioural and pharmacological point of view.
多发性硬化症是一种慢性炎症性脱髓鞘疾病,在 50-80%的患者中与持续性疼痛相关。虽然越来越多的文献记录了影响这些患者的疼痛类型,但这种病理的机制仍知之甚少,需要建立与多发性硬化症相关的慢性疼痛的动物模型。我们的研究目的是在两种大鼠实验性自身免疫性脑脊髓炎(EAE)模型中,对感觉异常进行特征描述,特别是与持续性疼痛相关的临床症状。这种行为特征测试了几种感觉模式,如机械和热(热/冷)痛觉过敏或感觉异常,并且在两个不同的肢体(后爪和尾巴)上探索了这些模式中的一些。我们的研究表明,虽然一种模型产生了更严重的运动障碍,但两种模型的动物都遭受机械性痛觉过敏和冷感觉异常,包括尾巴和后爪。虽然这些模式中的一些时间进程变化在两种模型之间的时间上有所偏移,但它们代表了多发性硬化症患者经历的感觉异常的良好模型。我们研究的第二部分旨在从药理学角度对最具代表性的模型(“EAE+环孢菌素”)进行特征描述,并表明加巴喷丁、度洛西汀和曲马多部分缓解了一些临床症状。我们的研究结果表明,在大鼠中,“EAE+环孢菌素”模型是一种多发性硬化症患者慢性感觉异常的良好模型,从行为和药理学角度来看都是如此。