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Effects of Vaccination with Altered Peptide Ligand on Chronic Pain in Experimental Autoimmune Encephalomyelitis an Animal Model of Multiple Sclerosis

机译:改变肽配体的疫苗接种对实验性自身免疫性脑脊髓炎(一种多发性硬化症的动物模型)的慢性疼痛的影响

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摘要

Neuropathic pain is a chronic symptom of multiple sclerosis (MS) and affects nearly half of all MS sufferers. A key instigator of this pain is the pro-inflammatory response in MS. We investigated the behavioral effects of immunization with a mutant peptide of myelin basic protein (MBP), termed altered peptide ligand (APL), known to initiate immune deviation from a pro-inflammatory state to an anti-inflammatory response in experimental autoimmune encephalomyelitis (EAE), an animal model of MS. Male and female Lewis rats were injected with vehicle control or with varying doses of 50 or 100 μg guinea pig MBP in combination with or without APL. APL-treated animals established significantly lower disease severity compared to encephalitogenic MBP-treated animals. Animals with EAE developed mechanical, but not thermal pain hypersensitivity. Mechanical pain sensitivities were either improved or normalized during periods of clinical disease in male and female APL-treated animals as compared to the encephalitogenic group. No significant changes to thermal latency were observed upon co-immunization with APL. Together these data indicate that APL ameliorates disease states and selectively mediates an analgesic effect on EAE animals.
机译:神经性疼痛是多发性硬化症(MS)的一种慢性症状,几乎影响所有MS患者的一半。这种疼痛的关键诱因是MS中的促炎反应。我们调查了髓鞘碱性蛋白(MBP)突变肽(称为改变的肽配体(APL))的免疫接种的行为效果,该突变肽已知可在实验性自身免疫性脑脊髓炎(EAE)中从促炎状态转变为抗炎反应),MS的动物模型。对雄性和雌性Lewis大鼠分别注射溶媒对照或不同剂量的50或100μg豚鼠MBP联合或不联合APL。与脑致病性MBP治疗的动物相比,APL治疗的动物的疾病严重程度明显降低。患有EAE的动物发生机械性疼痛过敏,但未出现热痛过敏。与致脑炎的组相比,在雄性和雌性APL治疗的动物中,在临床疾病期间,机械疼痛敏感性得以改善或恢复正常。与APL共同免疫后,未观察到热潜伏期的显着变化。这些数据一起表明,APL改善了疾病状态,并选择性地介导了对EAE动物的镇痛作用。

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