Namer Barbara, Ørstavik Kirstin, Schmidt Roland, Mair Norbert, Kleggetveit Inge Petter, Zeidler Maximillian, Martha Theresa, Jorum Ellen, Schmelz Martin, Kalpachidou Theodora, Kress Michaela, Langeslag Michiel
Department of Physiology and Pathophysiology, University of Erlangen-Nuremberg, Erlangen, Germany.
Department of Anesthesiology, Heidelberg University, Mannheim, Germany.
Front Neurol. 2017 Jul 14;8:335. doi: 10.3389/fneur.2017.00335. eCollection 2017.
The first symptom arising in many Fabry patients is neuropathic pain due to changes in small myelinated and unmyelinated fibers in the periphery, which is subsequently followed by a loss of sensory perception. Here we studied changes in the peripheral nervous system of Fabry patients and a Fabry mouse model induced by deletion of α-galactosidase A (Gla). The skin innervation of Gla mice resembles that of the human Fabry patients. In Fabry diseased humans and Gla mice, we observed similar sensory abnormalities, which were also observed in nerve fiber recordings in both patients and mice. Electrophysiological recordings of cultured Gla nociceptors revealed that the conductance of voltage-gated Na and Ca currents was decreased in Gla nociceptors, whereas the activation of voltage-gated K currents was at more depolarized potentials. Conclusively, we have observed that reduced sensory perception due to small-fiber degeneration coincides with altered electrophysiological properties of sensory neurons.
许多法布里病患者出现的首个症状是周围小的有髓鞘和无髓鞘纤维发生变化所致的神经性疼痛，随后会出现感觉丧失。在此，我们研究了法布里病患者以及因α - 半乳糖苷酶A（Gla）缺失诱导的法布里病小鼠模型的外周神经系统变化。Gla小鼠的皮肤神经支配类似于人类法布里病患者。在法布里病患者和Gla小鼠中，我们观察到了相似的感觉异常，在患者和小鼠的神经纤维记录中也观察到了这种异常。对培养的Gla伤害感受器的电生理记录显示，Gla伤害感受器中电压门控钠电流和钙电流的传导性降低，而电压门控钾电流的激活处于更正的去极化电位。总之，我们观察到由于小纤维变性导致的感觉减退与感觉神经元电生理特性的改变同时出现。
