Genetic pain loss disorders
Genetic pain loss disorders
复制标题
DOI：
10.1038/s41572-022-00365-7
复制
发表时间：
2022-06-16
影响因子：
81.5
通讯作者：
Kurth, Ingo
中科院分区：
文献类型：
--
作者：
Lischka, Annette;Lassuthova, Petra;Kurth, Ingo
遗传性疼痛丧失障碍是一组异质性疾病，其特征在于疼痛感降低。遗传性疼痛缺失包括先天性疼痛不敏感症（CIP）、遗传性感觉神经病变，如果涉及自主神经，还包括遗传性感觉和自主神经病变（HSAN）。这种异质性疾病突出了伤害性感受在保护组织免受损伤中的重要作用。遗传性疼痛丧失的患者有复发性损伤，烧伤和愈合不良的伤口作为疾病的标志。CIP和HSAN是由>20个基因中的致病性遗传变异引起的，这些基因导致发育缺陷、神经变性或外周损伤感知神经元的神经元兴奋性改变。这些遗传变异导致钠通道过度活跃、血红素代谢紊乱、网格蛋白介导的转运改变以及影响表观遗传标记、长非编码RNA和重复元件的基因调控机制受损。疼痛消失障碍的治疗主要是对症治疗，但第一个靶向治疗正在测试中。相反，慢性疼痛仍然是尚未解决的最大医学挑战之一，与疼痛减轻相关的基因和机制为镇痛药提供了新的靶点。鉴于已经取得的进展，未来几年在疼痛丧失障碍的靶向治疗和基于这些遗传疾病的知识开发创新疼痛药物方面都很有希望。
Genetic pain loss disorders are a heterogeneous group of diseases that are characterized by reduced pain sensation. This Primer discusses the epidemiology, pathophysiology, diagnosis and treatment of these disorders.Genetic pain loss includes congenital insensitivity to pain (CIP), hereditary sensory neuropathies and, if autonomic nerves are involved, hereditary sensory and autonomic neuropathy (HSAN). This heterogeneous group of disorders highlights the essential role of nociception in protecting against tissue damage. Patients with genetic pain loss have recurrent injuries, burns and poorly healing wounds as disease hallmarks. CIP and HSAN are caused by pathogenic genetic variants in >20 genes that lead to developmental defects, neurodegeneration or altered neuronal excitability of peripheral damage-sensing neurons. These genetic variants lead to hyperactivity of sodium channels, disturbed haem metabolism, altered clathrin-mediated transport and impaired gene regulatory mechanisms affecting epigenetic marks, long non-coding RNAs and repetitive elements. Therapies for pain loss disorders are mainly symptomatic but the first targeted therapies are being tested. Conversely, chronic pain remains one of the greatest unresolved medical challenges, and the genes and mechanisms associated with pain loss offer new targets for analgesics. Given the progress that has been made, the coming years are promising both in terms of targeted treatments for pain loss disorders and the development of innovative pain medicines based on knowledge of these genetic diseases.