The skin, our largest sensory organ, serves as a vital protective barrier that is susceptible to injury and has remarkable regenerative abilities. Studies indicate that cutaneous nociceptors influence protective immunity. Yet, the full impact of nociceptor or sensory neuron activity on other skin-resident cells in both healthy and injured skin is not well understood. To tackle this, we apply an integrative approach combining neuronal manipulation techniques, single-cell transcriptomics, and detailed analysis of skin resident cells, aiming to reveal specific nociceptor-mediated cellular interactions that shape skin physiology.