TRP Channels as Molecular Transducers of Cutaneous Photosensitivity: Mechanisms and Clinical Implications

Cutaneous photosensitivity is one of the most common skin reactions linked to both systemic and topical drug use, and it can manifest in the form of phototoxicity and/or photoallergy. Both reactions are triggered by the exposure of a photosensitive drug to UV radiation, but they differ in the time interval until the onset of symptoms, whether they are dose-dependent, and to what extent the immune system becomes involved. At molecular level, these photosensitive drugs absorb UV energy and then release it through reactions that generate harmful byproducts including reactive oxygen species, damaging skin cells. Less understood is how these photochemical events are translated into clinical manifestations, such as pain, redness, and inflammation. A main role in this translation seems to be attributed to Transient Receptor Potential (TRP) channels, especially TRPA1 and TRPV1 which are known to be activated or modulated by light and are also sensitive to reactive molecules produced during drug photoreactions. Alongside TRP channels, a family of non-visual opsins, originally identified in the eye but now found in keratinocytes, melanocytes, and fibroblasts, appear to function as a separate, parallel light-sensing system in the skin. Together, these two systems may explain how UV-activated drugs and their byproducts give rise to the clinical symptoms of photosensitivity, potentially through a neuroendocrine-like signalling route where skin cells send signals post-UV exposure to nearby nerve endings. However, most current research treats TRP channels and opsins as separate entities, leaving the connection between these two pathways unclear.