Is it possible to develop an animal model of fibromyalgia?
Is it possible to develop an animal model of fibromyalgia?
复制标题
是否有可能建立纤维肌痛的动物模型？
DOI：
10.1016/j.pain.2009.07.032
复制
发表时间：
2009
期刊：
影响因子：
7.4
通讯作者：
Sluka,KathleenA
中科院分区：
文献类型：
--
作者：
Sluka,KathleenA
疾病状态的动物模型是开发新疗法以及研究潜在机制的宝贵工具。疾病的动物模型应该模拟疾病的症状和病理学，并且重要的是预测有效的治疗。纤维肌痛是一种独特的疼痛综合征，因为它是由症状诊断，而不是由潜在的病理。相比之下，关节炎疾病除了患者症状外还通过病理学诊断。纤维肌痛的症状包括广泛的疼痛，包括躯干，以及18个不同压痛点的压力刺激疼痛。纤维肌痛综合征（FMS）也与许多其他症状有关，包括疲劳，睡眠障碍和心理障碍，如抑郁和焦虑。这些症状的患病率在人群中各不相同，高达80%的人群发生疲劳，90%的人群发生睡眠障碍，40%的人群发生抑郁症（在[9]中进行了综述）。因此，理想的FMS动物模型应包括广泛的疼痛和相关症状。在人类受试者中，已经发现了一些潜在的病理变化，但FMS的起始原因尚未确定。神经内分泌功能障碍，神经递质的变化，神经感觉障碍，以及遗传易感性已牵连在纤维肌痛。下丘脑-垂体-肾上腺（HPA）轴也受到影响;皮质醇反应迟钝，生长激素调节异常[1]。纤维肌痛患者的脑脊液中发现5-羟色胺减少，P物质和神经生长因子增加[1，9]，中枢放大和疼痛中枢抑制减少[1，9]。此外，FMS具有很强的家族聚集性，并且有证据表明在胆碱能、多巴胺能和儿茶酚胺能系统中存在基因多态性（综述见[1，9]）。基于多个系统的广泛变化，有人提出有多个原因，FMS是具有相似症状的多种综合征的表现。因此，动物模型的开发是困难的。因此，多种潜在的动物模型可能是合适的。在这个问题上，Nagakura和同事[6]通过递送利血平来调节生物胺（5-羟色胺，去甲肾上腺素和多巴胺），利血平消耗全身的生物胺，包括外周和CNS。该动物模型导致肌肉和皮肤机械性痛觉过敏、CNS中生物胺的预期损失以及伴随的抑郁。在该模型中发现的痛觉过敏被在FMS中具有临床功效的药物、抗抑郁药和抗惊厥药逆转，但不被那些没有临床功效的药物逆转，即，非甾体抗炎药。因此，该模型模拟了具有广泛的机械性痛觉过敏和抑郁的FMS的症状、具有生物胺减少的FMS的病理学以及用于治疗FMS的药理学特征。它-
Animal models of disease states are valuable tools for development of new treatments, as well as examining underlying mechanisms. An animal model of disease should mimic the symptoms and pathology of the disease and importantly be predictive of effective treatments. Fibromyalgia is a unique pain syndrome because it is diagnosed by symptoms, not by underlying pathology. In contrast, arthritic diseases are diagnosed by pathology in addition to patient symptoms. The symptoms of fibromyalgia include widespread pain, which includes the trunk, and pain to pressure stimuli at 18 distinct tender points. Fibromyalgia syndrome (FMS) is also associated with a number of other symptoms including fatigue, sleep disturbances, and psychological disturbances, such as depression and anxiety. The prevalence of these symptoms varies across the population, with fatigue occurring in up to 80% of the population, sleep disturbances in 90% and depression occurring in 40%(reviewed in [9]). Thus, an animal model of FMS ideally should include widespread pain and the associated symptoms. In human subjects some underlying pathological changes have been discovered, yet the initiating cause for FMS is yet undefined. Neuroendocrine dysfunction, neurotransmitter changes, neurosensory disturbances, as well as genetic predispositions have been implicated in fibromyalgia. The hypothalamic–pituitary–adrenal (HPA) axis is also implicated; there are blunted cortisol responses and abnormal growth hormone regulation [1]. Decreased serotonin and increased substance P and nerve growth factor are found in the cerebrospinal fluid of patients with fibromyalgia [1, 9], as is central amplification and reduced central inhibition of pain [1, 9]. Further, there is a strong familial aggregation for FMS, and evidence for polymorphisms of genes in the serotoninergic, dopaminergic and catecholaminergic systems (reviewed in [1, 9]). Based on the widespread changes in multiple systems, some have suggested that there are multiple causes and that FMS is a manifestation of multiple syndromes with similar symptoms. The development of an animal model is therefore difficult. Thus, multiple potential animal models could be appropriate.In this issue, Nagakura and colleagues [6] modulated the biogenic amines (serotonin, noradrenaline and dopamine) by delivering reserpine, which depletes biogenic amines throughout the body including both the peripheral and CNS. The animal model results in muscle and cutaneous mechanical hyperalgesia, an expected loss of the biogenic amines in the CNS, and accompanying depression. The hyperalgesia found in this model is reversed by drugs that have clinical efficacy in FMS, antidepressants and anticonvulsants, but not by those without clinical efficacy viz., non-steroidal anti-inflammatory drugs. As such the model mimics the symptoms of FMS with widespread mechanical hyperalgesia and depression, the pathology of FMS with decreases in biogenic amines, and the pharmacological profile for treatment of FMS. It re-