Mental Stress in Atopic Dermatitis – Neuronal Plasticity and the Cholinergic System Are Affected in Atopic Dermatitis and in Response to Acute Experimental Mental Stress in a Randomized Controlled Pilot Study

Abstract

RationaleIn mouse models for atopic dermatitis (AD) hypothalamus pituitary adrenal axis (HPA) dysfunction and neuropeptide-dependent neurogenic inflammation explain stress-aggravated flares to some extent. Lately, cholinergic signaling has emerged as a link between innate and adaptive immunity as well as stress responses in chronic inflammatory diseases. Here we aim to determine in humans the impact of acute stress on neuro-immune interaction as well as on the non-neuronal cholinergic system (NNCS).MethodsSkin biopsies were obtained from 22 individuals (AD patients and matched healthy control subjects) before and after the Trier social stress test (TSST). To assess neuro-immune interaction, nerve fiber (NF)-density, NF-mast cell contacts and mast cell activation were determined by immunohistomorphometry. To evaluate NNCS effects, expression of secreted mammal Ly-6/urokinase-type plasminogen activator receptor-related protein (SLURP) 1 and 2 (endogenous nicotinic acetylcholine receptor ligands) and their main corresponding receptors were assessed by quantitative RT-PCR.ResultsWith respect to neuro-immune interaction we found higher numbers of NGF+ dermal NF in lesional compared to non-lesional AD but lower numbers of Gap43+ growing NF at baseline. Mast cell-NF contacts correlated with SCORAD and itch in lesional skin. With respect to the NNCS, nicotinic acetylcholine receptor α7 (α7nAChR) mRNA was significantly lower in lesional AD skin at baseline. After TSST, PGP 9.5+ NF numbers dropped in lesional AD as did their contacts with mast cells. NGF+ NF now correlated with SCORAD and mast cell-NF contacts with itch in non-lesional skin. At the same time, SLURP-2 levels increased in lesional AD skin.ConclusionsIn humans chronic inflammatory and highly acute psycho-emotional stress interact to modulate cutaneous neuro-immune communication and NNCS marker expression. These findings may have consequences for understanding and treatment of chronic inflammatory diseases in the future.

Reduced stress and inflammatory responsiveness in experienced meditators compared to a matched healthy control group

“…The LTM group also had a smaller inflammatory response to capsaicin. Importantly, the magnitude of inflammatory response to capsaicin was positively associated with the magnitude of the cortisol response, which supports previous evidence that psychological stress potentiates the neurogenic inflammatory response (Arck et al, 2003; Joachim et al, 2007; Kimata, 2003; Liu et al, 2013; Pavlovic et al, 2008; Peters et al, 2014, 2004; Singh et al, 1999). These observations confirm and extend our previous findings, which showed that individuals randomized to an 8-week MBSR intervention had smaller capsaicin-induced flare responses post-training, relative to individuals randomized to a validated active control condition (MacCoon et al, 2012; Rosenkranz et al, 2012).…”

Mast cell‐neural interactions contribute to pain and itch

“…Interestingly, the exposure of patients with AD to acute Trier Social Stress Test (TSST) resulted in decreased numbers of NGF + and PGP 9.5 + fibers and decreased contacts between PGP 9.5 + fibers and tryptase + mast cells in the lesional skin, whereas these parameters increased, rather than decreased, in the nonlesional skin. In addition, a significant positive correlation between itch and nerve fiber‐mast cell contacts in the nonlesional (after TSST) or lesional (before TSST) skin was noted . In another study, stress induced by video games or frequently ringing mobile phone increased allergen‐induced skin wheal reactions and serum levels of SP, VIP, and NGF in AD patients, but not in patients with allergic rhinitis or in healthy controls .…”

Endotypes of allergic diseases and asthma: An important step in building blocks for the future of precision medicine

“…At the same time, expression of secreted mammal Ly-6/urokinasetype plasminogen activator receptor-related levels (a marker for NNCS activation) increased in lesional AD skin. 113 The mixed type 2/Th17 endotype The mixed Th17/Th2 endotype is not rare in asthma, CRS or AD. Th2 cells can differentiate into dual-positive Th2/Th17 cells 114 and these cells were identified in the BAL fluid of asthmatic patients and related to glucocorticoid resistance in vitro and airway obstruction and hyperreactivity.…”