Biology subjects

Menzel, A. D.

Publications and source records attributed to Menzel, A. D..

3 recordsLinked to original sources

bioRxiv2026

Clonazepam activates the transient receptor potential melastatin 8 (TRPM8) ion channel

Benzodiazepines represent a major class of drugs prescribed as treatments for anxiety, insomnia and seizures. They act by engaging GABAA receptors in the central nervous system to depress neuronal excitability. Here, the polypharmacology of benzodiazepines was explored by studying their engagement of human TRP channels revealing clonazepam acts as a robust and selective activator of the TRPM8 ion channel. Clonazepam-evoked Ca2+ signals were observed in cells expressing human TRPM8 channels, and in mouse trigeminal neurons. These responses were completely blocked by pharmacological or genetic inhibition of TRPM8 function. This discovery likely explains why clonazepam is an effective treatment for the painful oral condition known as burning mouth disorder, where local activation of TRPM8 channels in sensory neurons mitigates the painful symptoms of this disease.

neuroscience↗

bioRxiv2023

Keratinocyte Piezo1 drives paclitaxel-induced mechanical hypersensitivity

Recent work demonstrates that epidermal keratinocytes are critical for normal touch sensation. However, it is unknown if keratinocytes contribute to touch evoked pain and hypersensitivity following tissue injury. Here, we used inhibitory optogenetic and chemogenetic techniques to determine the extent to which keratinocyte activity contributes to the severe neuropathic pain that accompanies chemotherapeutic treatment. We found that keratinocyte inhibition largely alleviates paclitaxel-induced mechanical hypersensitivity. Furthermore, we found that paclitaxel exposure sensitizes mouse and human keratinocytes to mechanical stimulation through the keratinocyte mechanotransducer Piezo1. These findings demonstrate the contribution of non-neuronal cutaneous cells to neuropathic pain and pave the way for the development of new pain-relief strategies that target epidermal keratinocytes and Piezo1. SummarySensitization of the keratinocyte mechanotransducer Piezo1 drives paclitaxel-induced touch pain.

neuroscience↗

bioRxiv2020

Piezo1 Mediates Keratinocyte Mechanotransduction

Epidermal keratinocytes mediate touch sensation by detecting and encoding tactile information to sensory neurons. However, the specific mechanotransducers that enable keratinocytes to respond to mechanical stimulation are unknown. Here, we found that the mechanically-gated ion channel Piezo1 is the major keratinocyte mechanotransducer. Keratinocyte expression of Piezo1 is critical for normal sensory afferent firing and behavioral responses to mechanical stimuli.

neuroscience↗