From the Brain-Skin Connection: The Neuroendocrine-Immune Misalliance of Stress and Itch

Abstract

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

Mast cell–driven skin inflammation is impaired in the absence of sensory nerves

“…[61][62][63][64][65][66][67] More specifically, the activation of neuropeptide-releasing nerve fibers by MCs and vice versa has been implicated in aggravating cutaneous pruritogenic inflammation as well as bronchial hyperreactivity, hypersecretion, eosinophilia, and tissue remodeling. [68][69][70][71][72][73][74] Further detailed characterization of the complex interactions between SNs and MCs will increase understanding of the pathology of several inflammatory and allergic diseases that involve both MC-driven and SN-mediated signals. Targeting the interactions between SNs and MCs ideally will lead to the development of novel therapeutic strategies.…”

Functional magnetic resonance imaging in dermatology: The skin, the brain and the invisible

“…[6][7][8] However, under stress, the HPA axis may be altered resulting in proinflammatory hormonal effects, resistance of tissue receptors to glucocorticoids and mast cell activation in the skin. [6,9] In addition, a brain-derived nerve growth factor can mediate or enhance skin inflammation culminating in a "nervous breakdown of the skin," which manifests as a stress-induced exacerbation of an inflammatory skin disease. [7,8,10] Indeed, there are numerous dermatological conditions strongly influenced by stress such as atopic eczema, psoriasis, pruritus or hyperhidrosis.…”

Medicinal chemistry of the vanilloid (Capsaicin) TRPV1 receptor: current knowledge and future perspectives

“…Conversely, overproduction of SP has been suggested to play a role in the pathobiology of psoriasis [Naukkarinen et al, 1993;Raychaudhuri et al, 1998]. Indeed, topical capsaicin cream is beneficial in patients with psoriasis [Bernstein et al, 1986], although it is still unclear to what degree this beneficial action may be attributed to the anti-pruritic effect of capsaicin [Arck and Paus, 2006]. Nonetheless, there is anecdotal evidence that cutaneous nerve damage results in the clearance of psoriatic plaques [Farber et al, 1990].…”