https://scholars.lib.ntu.edu.tw/handle/123456789/519535
標題: | Burning pain: Axonal dysfunction in erythromelalgia | 作者: | Farrar M.A. MING-JEN LEE Howells J. Andrews P.I. Lin C.S.-Y. |
關鍵字: | Erythromelalgia; Excitability; Mexiletine; Pain; SCN9A; Sodium channel | 公開日期: | 2017 | 出版社: | Lippincott Williams and Wilkins | 卷: | 158 | 期: | 5 | 起(迄)頁: | 900-911 | 來源出版物: | Pain | 摘要: | Erythromelalgia (EM) is a rare neurovascular disorder characterized by intermittent severe burning pain, erythema, and warmth in the extremities on heat stimuli. To investigate the underlying pathophysiology, peripheral axonal excitability studies were performed and changes with heating and therapy explored. Multiple excitability indices (stimulus-response curve, strength-duration time constant (SDTC), threshold electrotonus, and recovery cycle) were investigated in 23 (9 EMSCN9A+ and 14 EMSCN9A-) genetically characterized patients with EM stimulating median motor and sensory axons at the wrist. At rest, patients with EM showed a higher threshold and rheobase (P < 0.001) compared with controls. Threshold electrotonus and current-voltage relationships demonstrated greater changes of thresholds in both depolarizing and hyperpolarizing preconditioning electrotonus in both EM cohorts compared with controls in sensory axons (P < 0.005). When average temperature was raised from 31.5°C to 36.3°C in EMSCN9A+ patients, excitability changes showed depolarization, specifically SDTC significantly increased, in contrast to the effects of temperature previously established in healthy subjects (P < 0.05). With treatment, 4 EMSCN9A+ patients (4/9) reported improvement with mexiletine, associated with reduction in SDTC in motor and sensory axons. This is the first study of primary EM using threshold tracking techniques to demonstrate alterations in peripheral axonal membrane function. Taken together, these changes may be attributed to systemic neurovascular abnormalities in EM, with chronic postischaemic resting membrane potential hyperpolarization due to Na + /K + pump overactivity. With heating, a trigger of acute symptoms, axonal depolarization developed, corresponding to acute axonal ischaemia. This study has provided novel insights into EM pathophysiology. ? Copyright 2017 The Author(s). |
URI: | https://www.scopus.com/inward/record.uri?eid=2-s2.0-85021308494&doi=10.1097%2fj.pain.0000000000000856&partnerID=40&md5=a6b5226da118074ef7fcc66fe0cb2c88 https://scholars.lib.ntu.edu.tw/handle/123456789/519535 |
ISSN: | 0304-3959 | DOI: | 10.1097/j.pain.0000000000000856 | SDG/關鍵字: | acetylsalicylic acid; amitriptyline; antihistaminic agent; carbamazepine; clonazepam; clonidine; gabapentin; imipramine; mexiletine; midodrine; misoprostol; phenoxybenzamine; pregabalin; propranolol; SCN9A protein, human; sodium channel Nav1.7; adenosine triphosphatase (potassium sodium); sodium channel Nav1.7; adolescent; adult; aged; Article; axon; axonal injury; burning pain; child; clinical article; controlled study; depolarization; electric potential; erythromelalgia; excitability; heating; human; hyperpolarization; male; membrane steady potential; nerve fiber membrane; pain; pathophysiology; priority journal; stimulus response; temperature; biological model; case control study; complication; computer simulation; erythromelalgia; female; genetics; middle aged; mutation; nerve conduction; pain; pathology; physiology; severity of illness index; young adult; axon; clinical feature; cohort analysis; electrical potential parameters; gene mutation; mathematical model; molecular pathology; motor nerve; motor nerve conduction; muscle action potential; nerve excitability; nerve stimulation; peripheral nerve; preschool child; recovery cycle; sensory nerve; strength duration time constant; threshold electrotonus; wrist; Adolescent; Adult; Aged; Axons; Case-Control Studies; Child; Computer Simulation; Erythromelalgia; Female; Humans; Male; Middle Aged; Models, Biological; Mutation; NAV1.7 Voltage-Gated Sodium Channel; Neural Conduction; Pain; Severity of Illness Index; Temperature; Young Adult |
顯示於: | 醫學系 |
在 IR 系統中的文件,除了特別指名其著作權條款之外,均受到著作權保護,並且保留所有的權利。