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Papers of the Week


Papers: 26 April 2025 - 2 May 2025


2025 Apr 25


eNeuro


40280765

Editor's Pick

Investigating Mechanically Activated Currents from Trigeminal Neurons of Non-Human Primates.

Authors

Lindquist KA, Mecklenburg JM, Hovhannisyan AH, Ruparel SB, , Akopian AN

Abstract

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 non-human primates (NHP). MA currents triggered by a piezo-actuator 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 4 S-type and 5 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 one group, showed MA currents. We additionally used immunohistochemistry to confirm presence of known sensory neuronal types such as un-myelinated peptidergic CGRP/trpV1, un-myelinated non-peptidergic MrgprD and CGRP/trpV1, and myelinated peptidergic CGRP/trpV1 and non-peptidergic CGRP and PV NHP TG neurons. Overall, marmoset TG neurons and associated MA currents have many similarities compared to 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 fast inactivating MA currents. Understanding the mechanical responses in trigeminal (TG) neurons is pivotal for elucidating the mechanisms of somatosensation and gaining insights into the cellular basis of acute and chronic pain in head and neck area. Mechanically activated (MA) currents have mainly been characterized in rodent sensory neurons. However, extrapolating these findings to humans may have significant implications. Thus, identifying specific properties of MA currents from non-human primates (NHPs) is of fundamental importance, underscoring the relevance of this study. MA currents triggered by a piezo-actuator were studied in NHP TG neurons using patch-clamp electrophysiology. Based on electrical properties of neurons, 9 distinct types of NHP TG neurons were identified. Overall, NHP TG neurons have many similarities with reported properties of mouse dorsal root ganglion (DRG) and TG neurons. However, there are notable differences such as a low percentage of neurons responding to mechanical stimuli among the smaller TG neurons and an absence of fast inactivating MA currents.