In this studies we investigated the role of chronic UV exposure on the neurosensory system of the skin by simulating long-term phototherapy. Our results suggest that repeated subinflammatory UV exposure induces neurogenic inflammation through CGRP and other mediators. These facts do not only play a role in the chronic UV exposure of UV therapy, but is an important effect also on the whole population which is chronically exposed to UV irradiation. All effects seem to be possibly prevented by using a broadband sunscreen that inhibit neurogenic inflammation and could possibly prevent the development of UVR induced skin cancer. To investigate the existence and growth of nerve fibres in the upper skin layer we investigated the amount of sensory nerve fibres innervating the tumor tissues, using the panneural marker PGP 9.5 on non melanoma skin cancer. Tumor tissue of BCC and the group of NMSC comprising AK, Cis and SCC show a higher innervation density than adjacent non-tumor epidermal tissue. In addition,the innervation density of tumor and adjacent non-tumor tissue in BCC is higher than in the group of NMSC. Whether innervation density is relevant for the pathogenesis of NMSC and possibly may contribute to the promotion of the different types of NMSC in photo-damaged skin, or represents an epiphenomenon, remains to be determined. We expected that the neurosensory system of the skin has also an importance in the immune reactions of the skin of PLE patients. Pretreatment with capsaicin cream significantly reduced the number of PGP 9.5-IR epidermal nerve fibers. However, it did not significantly affect the induction of PLE, after repeated SSR exposure. Based on the experimental nerve depletion conditions and the photoprovocation protocol we had used in this study, we conclude that epidermal nerve fibers, and neuropeptides within these fibers, do not play a significant role in the induction of the clinical signs of PLE.