A specialized population of hair afferents dedicated to transmitting mechanical itch

Hairs serve as sensory structures that are crucial for perceiving environmental cues through interactions with sensory endings. Depigmented and demedullated atypical hairs exhibit a limited distribution on mammalian skin and have not been extensively studied. In this study, we identify a specific type of hair, termed vellus-like hairs (VLHs), which are enriched in the postauricular region and on the hindpaws of mice. These hairs are innervated by Aβ low-threshold mechanoreceptors (LTMRs) that co-express Toll-like receptor 5 and Calbindin1 (TLR5^Calb1). Genetic ablation or silencing of these hair afferents eliminated mechanical itch generated by gentle VLH stroking or indentation under both physiological and pathological conditions. Conversely, optogenetic activation of TLR5^Calb1 hair afferents evoked itch behaviors. Mechanosensitive Piezo2 channels in TLR5^Calb1 Aβ-LTMRs function as key mechanotransducers for mechanical itch signaling. Our study sheds light on the previously poorly understood somatosensory physiology of unique hairs, emphasizing the significant role of TLR5^Calb1 Aβ-LTMRs in itch transmission.