Departments of Pharmacology and.
Anesthesiology, College of Medicine, The University of Arizona Health Sciences, Tucson, AZ, United States.
Pain. 2019 May;160(5):1007-1018. doi: 10.1097/j.pain.0000000000001486.
Neurofibromatosis type 1 (NF1) is the most common of a group of rare diseases known by the term, "Neurofibromatosis," affecting 1 in 3000 to 4000 people. NF1 patients present with, among other disease complications, café au lait patches, skin fold freckling, Lisch nodules, orthopedic complications, cutaneous neurofibromas, malignant peripheral nerve sheath tumors, cognitive impairment, and chronic pain. Although NF1 patients inevitably express pain as a debilitating symptom of the disease, not much is known about its manifestation in the NF1 disease, with most current information coming from sporadic case reports. Although these reports indicate the existence of pain, the molecular signaling underlying this symptom remains underexplored, and thus, we include a synopsis of the literature surrounding NF1 pain studies in 3 animal models: mouse, rat, and miniswine. We also highlight unexplored areas of NF1 pain research. As therapy for NF1 pain remains in various clinical and preclinical stages, we present current treatments available for patients and highlight the importance of future therapeutic development. Equally important, NF1 pain is accompanied by psychological complications in comorbidities with sleep, gastrointestinal complications, and overall quality of life, lending to the importance of investigation into this understudied phenomenon of NF1. In this review, we dissect the presence of pain in NF1 in terms of psychological implication, anatomical presence, and discuss mechanisms underlying the onset and potentiation of NF1 pain to evaluate current therapies and propose implications for treatment of this severely understudied, but prevalent symptom of this rare disease.
神经纤维瘤病 1 型(NF1)是一组罕见疾病的统称,术语为“神经纤维瘤病”,每 3000 到 4000 人中就有 1 人患有这种疾病。NF1 患者除其他疾病并发症外,还表现出咖啡牛奶斑、皮肤褶皱雀斑、Lisch 结节、骨科并发症、皮肤神经纤维瘤、恶性外周神经鞘瘤、认知障碍和慢性疼痛。尽管 NF1 患者不可避免地会表现出疼痛,这是该疾病的一种衰弱症状,但人们对 NF1 疾病中疼痛的表现知之甚少,大多数当前信息来自零星的病例报告。尽管这些报告表明存在疼痛,但这种症状的分子信号仍未得到充分探索,因此,我们在 3 种动物模型(小鼠、大鼠和迷你猪)中概述了围绕 NF1 疼痛研究的文献:小鼠、大鼠和迷你猪。我们还强调了 NF1 疼痛研究中未探索的领域。由于 NF1 疼痛的治疗仍处于各种临床和临床前阶段,我们为患者提供了目前可用的治疗方法,并强调了未来治疗开发的重要性。同样重要的是,NF1 疼痛伴随着与睡眠、胃肠道并发症和整体生活质量相关的共病的心理并发症,这使得对这种研究不足的 NF1 现象的研究变得至关重要。在这篇综述中,我们从心理影响、解剖存在的角度来剖析 NF1 中疼痛的存在,并讨论 NF1 疼痛发作和加剧的潜在机制,以评估当前的治疗方法,并为这种严重研究不足但普遍存在的罕见疾病的症状提出治疗建议。
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