Schmerz und Schmerzlosigkeit
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- 作者：Dr. M. J. Eberhardt ; Prof. Dr. A. Leffler
- 关键词：SchlüsselwörterNatriumkanal ; Mutation ; Kongenitale Schmerzunempfindlichkeit ; Schmerz ; Nozizeptoren
- 刊名：Der Schmerz
- 出版年：2017
- 出版时间：February 2017
- 年：2017
- 卷：31
- 期：1
- 页码：14-22
- 全文大小：
- 刊物类别：Medicine
- 刊物主题：Pain Medicine; Anesthesiology; Chiropractic Medicine; Psychotherapy;
- 出版者：Springer Medizin
- ISSN：1432-2129
- 卷排序：31
文摘
Voltage-gated sodium channels (Navs) are crucial for the generation and propagation of action potentials in all excitable cells, and therefore for the function of sensory neurons as well. Preclinical research over the past 20 years identified three Nav-isoforms in sensory neurons, namely Nav1.7, Nav1.8 and Nav1.9. A specific role for the function of nociceptive neurons was postulated for each. Whereas no selective sodium channel inhibitors have been established in the clinic so far, the relevance of all three isoforms regarding the pain sensitivity in humans is currently undergoing a remarkable verification through the translation of preclinical data into clinically manifest pictures. For the last ten years, Nav1.7 has been the main focus of clinical interest, as a large number of hereditary mutants were identified. The so-called “gain-of-function” mutations of Nav1.7 cause the pain syndromes hereditary erythromelalgia and paroxysmal extreme pain disorder. In addition, several Nav1.7 mutants were shown to be associated with small-fiber neuropathies. On the contrary, “loss-of-function” Nav1.7 mutants lead to a congenital insensitivity to pain. Recently, several gain-of-function mutations in Nav1.8 and Nav1.9 have been identified in patients suffering from painful peripheral neuropathies. However, another gain-of-function Nav1.9 mutation is associated with congenital insensitivity to pain. This review offers an overview of published work on painful Nav mutations with clinical relevance, and proposes possible consequences for the therapy of different pain symptoms resulting from these findings.