An Update on the Correlation Between Neuroimmunomodulation, Photodynamic Therapy (PDT), and Wound Healing: The Role of Mast Cells

This review presents some aspects of the complex relationship between neuroimmunomod- ulation, photodynamic therapy, and wound healing. This relationship is important because photodynamic therapy, currently used to treat chronic wounds, has numerous effects on so-called neuroimmunomodulation, or the influence the nervous system has on immune cells. Consequently, the cellular and molecular mechanisms of wound healing and the alterations of these mechanisms that lead to the formation of chronic wounds are first considered. This view is subsequently broadened to include the effects produced by neu- roimmunomodulation throughout the various phases of wound healing and the alterations produced in chronic wounds. Throughout the above, the role of mast cells, the main in- flammatory cells that play a key role in wound healing, is highlighted. In this context, mast cells, located in close anatomical and functional proximity to peripheral nerve endings, act as key neuroimmune intermediaries. Upon activation, mast cells release inflamma- tory mediators that directly influence wound tissue and sensitize nearby nerve fibers. In turn, peripheral nerves release neuropeptides that further modulate immune cell activity, vascular responses, and tissue repair processes. All of this is in turn linked to the clinical evidence that photodynamic therapy, by virtue of the cellular and molecular mechanisms involved, can indeed be considered involved in the healing of chronic wounds.