Keratinocyte Piezo1 drives paclitaxel-induced mechanical hypersensitivity. bioRxiv 2023 Dec 13
Date
01/04/2024Pubmed ID
38168305Pubmed Central ID
PMC10760029DOI
10.1101/2023.12.12.571332Abstract
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.
Author List
Mikesell AR, Isaeva E, Schulte ML, Menzel AD, Sriram A, Prahl MM, Shin SM, Sadler KE, Yu H, Stucky CLAuthors
Olena Isaeva PhD Assistant Professor in the Cell Biology, Neurobiology and Anatomy department at Medical College of WisconsinSeung Min Shin PhD Assistant Professor in the Anesthesiology department at Medical College of Wisconsin
Cheryl L. Stucky PhD Professor in the Cell Biology, Neurobiology and Anatomy department at Medical College of Wisconsin
