Lindquist Karen A, Mecklenburg Jennifer M, Hovhannisyan Anahit H, Ruparel Shivani B, Akopian Armen N
Department of Pharmacology and Physiology, School of Medicine, University of Texas Health Science Center at San Antonio, San Antonio, Texas 78229.
Integrated Biomedical Sciences (IBMS) Program, University of Texas Health Science Center at San Antonio, San Antonio, Texas 78229.
eNeuro. 2025 May 12;12(5). doi: 10.1523/ENEURO.0054-25.2025. Print 2025 May.
Pain sensation often involves mechanical modalities. Mechanically activated (MA) ion channels on sensory neurons underly responsiveness to mechanical stimuli. MA current properties have mainly been derived from rodent sensory neurons. This study aimed to address gaps in knowledge regarding MA current properties in trigeminal (TG) neurons of a higher-order species, common marmoset nonhuman primates (NHP). MA currents triggered by a piezoactuator were recorded in patch-clamp configuration. MA responses were associated with action potential (AP) properties, such as width, dV/dt on the falling phase, and presence/absence of AP firing in NHP TG neurons. According to responsiveness to mechanical stimuli and AP properties, marmoset TG neurons were clustered into four S-type and five M-type groups. S-type TG neurons had broader AP with two dV/dt peaks on the AP falling phase. Only one S-type group of NHP TG neurons produced small MA currents. M-type TG neurons had narrow AP without two dV/dt peaks on the AP falling phase. M-type NHP TG neurons, except for one group, showed MA currents. We additionally used immunohistochemistry to confirm the presence of known sensory neuronal types such as unmyelinated peptidergic CGRP/trpV1, unmyelinated nonpeptidergic MrgprD and CGRP/trpV1, and myelinated peptidergic CGRP/trpV1 and nonpeptidergic CGRP and PV NHP TG neurons. Overall, marmoset TG neurons and associated MA currents have many similarities compared with reported data from mouse sensory neurons. However, there are notable differences such as lower percentage of small NHP TG neurons responding to mechanical stimuli and absence of fast inactivating MA currents.
痛觉通常涉及机械性感觉模式。感觉神经元上的机械激活(MA)离子通道是对机械刺激产生反应的基础。MA电流特性主要来自啮齿动物的感觉神经元。本研究旨在填补关于高等物种普通狨猴非人类灵长类动物(NHP)三叉神经(TG)神经元MA电流特性的知识空白。通过膜片钳配置记录由压电致动器触发的MA电流。MA反应与动作电位(AP)特性相关,如宽度、下降相的dV/dt以及NHP TG神经元中AP发放的有无。根据对机械刺激的反应性和AP特性,狨猴TG神经元被聚类为四个S型组和五个M型组。S型TG神经元的AP更宽,在AP下降相有两个dV/dt峰值。只有一组NHP TG神经元产生小的MA电流。M型TG神经元的AP较窄,在AP下降相没有两个dV/dt峰值。除一组外,M型NHP TG神经元均显示出MA电流。我们还使用免疫组织化学来确认已知感觉神经元类型的存在,如无髓鞘肽能CGRP/trpV1、无髓鞘非肽能MrgprD和CGRP/trpV1,以及有髓鞘肽能CGRP/trpV1和非肽能CGRP和PV NHP TG神经元。总体而言,与小鼠感觉神经元的报道数据相比,狨猴TG神经元及其相关的MA电流有许多相似之处。然而,也存在显著差异,如对机械刺激有反应的小NHP TG神经元比例较低,以及不存在快速失活的MA电流。