Human skin consists of a sophisticated network of nerve fibers and specialized sensory structures to transduce sensations of touch, vibration, temperature, and pain. Nerve fibers have dual functions: to transmit afferent sensory impulses to the central nervous system and to secrete mediators into the local environment. While many of these mediators are polypeptides (called neuropeptides), others are nonpeptide factors. These factors affect various biologic processes including inflammation, immunity, wound healing, and aging. Cutaneous neurobiology is an expanding field of research with increasing clinical implications. The presence of neuropeptide receptors on epidermal and dermal cells and the close anatomic relationship of nerve fibers with immune and nonimmune cells demonstrate the direct link between the sensory nervous system and the largest organ system of the human body, the skin. Neuropeptides (NPs) are a heterogeneous group of polypeptides ranging from 2 to greater than 40 amino acids in size. There are over 50 identified neuropeptides, 11 of which are found in human skin. Neuropeptides are released in response to a range of stimuli from pain and temperature to irritation in order to mediate diverse biologic processes related to injury, inflammation, infection, and wound healing.
[...] Vitiligo Vulgaris Vitiligo is a depigmenting disorder often presenting in a symmetric or segmental distribution. There are changes in neuropeptides distribution in affected skin. An increase in NPY, CGRP, and SP has been demonstrated, whereas no changes in VIP was observed, supporting the concept that neuropeptides are involved in the pathogenesis of vitiligo. Alopecia Areata Alopecia areata is characterized by nonscarring patches of hair loss. The pathogenesis is complex and unclear, as immunologic, genetic, environmental, and psychological factors are implicated; however, stressful life events may trigger or exacerbate the disease. [...]
[...] fibers; however, evidence exists that epidermal and dermal cells also produce neuropeptides and neurohormones. These cells include fibroblasts, keratinocytes, Langerhans' cells, macrophages, mast cells, melanocytes, endothelial cells, Merkel cells, and leukocytes. The distribution of neuropeptides varies depending on the body site. High levels of SP, NKA, and CGRP are found in areas with the greatest tactile sensation. Intermediate levels are found in the neck and face, whereas the lowest levels are present in the groin, arm, and thigh. Levels of VIP and peptide histidine methionine (PHM) are also highest in axillary skin, suggesting their role in axillary eccrine sweat production. [...]
[...] Histamine is well known for its pruritic effects especially in urticaria. However, in conditions such as atopic dermatitis the inability of antihistamines to eliminate itch suggest that other mediators are involved as well. Intradermal injection of SP, VIP, and somatostatin evokes pruritus; however, CGRP does not have pruritogenic effects in humans. Substance P is released from C neuron terminals by the action of mast cell tryptase on PAR-2 to directly cause itching and to induce mast cells to release histamine. [...]
[...] Urocanic acid exists in the epidermis primarily as the trans isomer. UVB (and UVC) radiation induces a trans-cis isomerization and considerable evidence supports a role for cis-urocanic acid (UCA) in UVR- induced immune suppression. Increasing evidence also suggests that mast cell products such as histamine are important in downstream systemic immunosuppression. Evidence suggests that sensory C fibers and mast cells form a functional unit with bidirectional effects. Cis-urocanic can activate mast cells by its effects on release of neuropeptides by afferent sensory nerves. [...]
[...] Its biologic effects in the skin are mediated predominantly by the NK- 1 receptor. Substance P leads to the activation of phospholipase increase in intracellular calcium, and subsequently the activation of nuclear factorkappa B (NF-κB). Substance P is a potent vasodilator, participating in the wheal and flare response in neurogenic inflammation. It directly acts on vascular smooth muscle and indirectly on the endothelium to enhance the production of nitric oxide, resulting in vasodilatation and increased vascular permeability. In human skin, SP is also released by free nerve endings in the dermal papilla and epidermis of human fingers, in Meissner's corpuscles, and near sweat gland ducts and blood vessels. [...]
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