From the brain-skin connection: the neuroendocrine-immune misalliance of stress and itch.
Perceived stress has long been allied with disturbances of the dynamic equilibrium established between the nervous, endocrine and immune systems, thus triggering or aggravating disease manifestation. Several common skin diseases are now acknowledged to be worsened by psychological stress, particularly immunodermatoses such as atopic dermatitis, psoriasis, seborrheic eczema, prurigo nodularis, lichen planus, chronic urticaria, alopecia areata and pruritus sine materia. Itch (pruritus) is perhaps the most common symptom associated with a majority of these inflammatory skin diseases, and acute as well as chronic stress perceptions are recognized to trigger or enhance pruritus. A wealth of mediators released systemically or locally in the skin in response to stress increase sensory innervation, upregulate the production of other pruritogenic agents, perpetuate (neurogenic) inflammation and lower the itch threshold. In the present review, we explore recent frontiers in both stress and pruritus research and portray the perpetuation of chronic skin inflammation and itch as a neuroendocrine-immune 'misalliance'. We argue that key candidate molecules of the stress response with strong pruritogenic potential, such as nerve growth factor, corticotropin-releasing hormone and substance P, and mast cells, which may be considered as 'central cellular switchboards of pruritogenic inflammation', need to be further explored systematically in order to develop more effective therapeutic combination strategies for itch management in chronic, stress-vulnerable inflammatory skin diseases.
Arck
Petra
P
Center for Internal Medicine and Dermatology, Charité, University Medicine Berlin, and Department of Dermatology, University Hospital Schleswig-Holstein, Lübeck, Germany. petra.arck@charite.de
Paus
Ralf
R
D000818:Animals; D001921:Brain / Q000502:physiology*; D006801:Humans; D007249:Inflammation / Q000523:psychology; D008407:Mast Cells / Q000276:immunology / Q000378:metabolism; D015213:Neuroimmunomodulation / Q000502:physiology; D009490:Neurosecretory Systems / Q000502:physiology*; D011537:Pruritus / Q000523:psychology*; D012867:Skin / Q000166:cytology / Q000276:immunology / Q000294:innervation*; D013315:Stress, Psychological / Q000503:physiopathology*