The neuro-cutaneous axis: the role of nerve cells in wound healing

This narrative review summarizes the primary regulatory function of the neurocutaneous axis in wound healing. Hemostasis, inflammation, proliferation, and remodeling are the four phases of skin wound healing. Neurons release neuropeptides like substance P (SP), calcitonin gene-related peptide (CGRP), and vasoactive intestinal peptide (VIP) along with neurotrophic factors. They initiate vasodilation and promote platelet aggregation during the hemostasis phase, regulate immune cell recruitment and activity during the inflammatory phase, promote keratinocyte migration, fibroblast activation, and angiogenesis during the proliferation phase, and participate in the ordered arrangement of collagen and neural reinnervation during the remodeling phase. Furthermore, the clearance of apoptotic cells by macrophage-mediated phagocytosis couples the resolution of inflammation with the onset of regeneration, forming a closed-loop mechanism through signal contact between the neuro-immune-skin cell network. Along with offering theoretical references for wound regeneration, this paper also examines focused therapeutic approaches such as neuropeptide delivery, the synergistic use of conductive materials and electrical stimulation, and stem cell and gene therapy.