Cellular and molecular changes in the skin driving increased nociception and pain during burn injury and repair.

Burn injuries are among the most frequent traumas associated with human activity and primarily affect the skin. Unlike other forms of tissue injury, burns produce a unique combination of extensive tissue destruction, rapid release of damage-associated signals, and profound alterations in cutaneous architecture. These injury-specific features generate a robust inflammatory environment and early neuroimmune activation that can transition into neuropathic pain. Together, they drive marked peripheral sensitization and, in some cases, evolve into pain chronification, substantially affecting long-term quality of life in burn survivors. This review synthesizes current evidence on how thermal injury reshapes the function of key cutaneous cell populations, including keratinocytes, epidermal stem cells, melanocytes, fibroblasts, and immune cells, and how these changes modulate nociceptor activity through inflammatory, neurotrophic, and neuroimmune pathways. Furthermore, we describe how burn-induced cellular dysregulation contributes to peripheral sensitization across the continuum of wound healing, from acute inflammation to tissue repair. By integrating emerging mechanistic insights, this review highlights therapeutic targets aimed at minimizing subacute pain and preventing or mitigating chronic pain after burn injury.