Life Sciences Faculties

Pain is a self-preservation mechanism, providing warning indicators associated with tissue damage. These indicators are perceived by nociceptive peripheral innervations with the ability to signal the brain. Nociceptive innervations are also a part of the infrastructure of various organs, yet the imprint their activity has on tissue physiology remains understudied. Here, we applied chemogenetics in mice to locally activate cutaneous TRPV1 innervations in naïve skin and found it triggered accelerated anagen onset. This was preceded by a rapid apoptosis of dermal macrophages mediated by neuropeptide calcitonin gene-related peptide (CGRP), followed by an induction of Osteopontin (Spp1)-expressing dermal fibroblasts. Spp1, an extracellular matrix protein and a hair growth promoting factor, was essential for the TRPV1-triggered induction of new regenerative cycling by dormant hair follicles. Specifically, macrophages responsiveness to CGRP was required for the changes in dermal fibroblasts. Finally, we show that epidermal abrasion induced Spp1-expressing dermal fibroblasts and hair growth via a TRPV1 neuron and CGRP dependent mechanism. Collectively, these data demonstrate a role for pain facilitating innervations in coordinating a cellular mechanism that promotes hair growth and the restoration of this important mechano- and thermo-protective barrier