Peptide-Based Approaches for Pain Relief and Healing in Wounds

A wound has been defined as a disruption of tissue integrity. Pain, bleeding, and the risk of infection are inherent features of wounds, while chronic wounds are often accompanied by serous exudate. Pain associated with chronic wounds is usually underestimated and inadequately addressed in routine clinical care, despite being considered by patients as one of the most burdensome factors affecting their quality of life. Traditionally, management of wound-related pain has relied primarily on systemic analgesics, commonly administered orally. However, recently, there has been accumulated interest in the potential of topical analgesics. Unfortunately, both systemic and local administrations of conventional analgesics (e.g., NSAIDs, opioids) might carry risks of adverse effects, including delayed wound healing and systemic absorption. In this review, we summarize current research on the use of local analgesia for painful wounds and explore the potential of topically applied peptides with analgesic activity as a promising alternative to conventional pain management strategies. We also discuss recent innovations in the development of therapeutic peptides, including those with anti-inflammatory and regenerative activities, which might further enhance outcomes in the wound healing process. Finally, we address challenges associated with topical peptide delivery across compromised skin barriers and examine strategies to overcome these limitations, while outlining future directions for formulation and clinical application of peptide-based wound therapies.