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Editorial ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Cell. Neurosci. | doi: 10.3389/fncel.2019.00521


  • 1University of Eastern Finland, Finland
  • 2University of California, Irvine, United States
  • 3Tufts University School of Medicine, United States

establishing the disease-specific role of mast cells. Many of these interesting novel lines of research are presented in the current collection.The present e-book consists of 17 articles including one brief research report, one hypothesis and theory article, seven original research articles, five reviews and three mini-reviews.Although the idea of the neuro-immune synapse is presented in direct or indirect manner in most of the papers, some of them are specifically devoted to this concept. Thus, Mittal et al., 2019Mittal et al., (doi: 10.3389/fncel.2019.00110) present the concept of neuro-immune synapse and the critical role of mast cells in neuroinflammation. In particular, they discuss the novel aspect of mast cell interaction with the nervous system through extracellular vesicles, tunneling nanotubes, and extracellular traps that may contribute to various pathological brain conditions. The paper by Magadmi et al. (2019Magadmi et al. ( , doi:10.3389/fncel.2019) is devoted to the organization of the neuro-immune synapse and suggests the contribution of the CADM1-dependent mechanism for adhesion of the key partners involved in the neuro-immune synapse. Siiskonen andHarvima, 2019 ( present the concept of the neuro-immune synapse for skin disorders. They reviewed the role of crosstalk between mast cells with sensory nerves as the contributors to neurogenic inflammation and pruritus in chronic skin inflammation.The most widely accepted role of mast cells is the promotion of pain states. Theoharides et al., 2019Theoharides et al., ( proposed that thalamic mast cells contribute to inflammation and pain in fibromyalgia by releasing multiple pro-inflammatory molecules which could either stimulate thalamic nociceptive neurons directly or activate microglia in the diencephalon. They also suggest stabilization of mast cells as the novel approach in treating this painful state. Richards et al., 2019Richards et al., ( demonstrate the discogenic back pain and mast cell/Proteinase Activated Receptor 2-mediated interactions in this disorder.In this collection, the role of meningeal mast cells as the triggers of migraine pain and local inflammation, originally proposed by the co-Editor of this e-book, T. Theoharidis, is presented in several papers. The group of Jansen-Olesen, in the original study, explored the role of the newly emerged migraine mediator PACAP as the trigger of degranulation of meningeal mast cells via the atypical orphan MRGB3-receptor (Pedersen et al., 2019(Pedersen et al., , experimental study for Koroleva et al., 2019Koroleva et al., ( shows, by using mice deficient in mast cells, that the putative migraine mediator extracellular ATP strongly activates nociceptive firing in meningeal trigeminal afferents via degranulation of resident mast cells and release of serotonin together with the direct excitatory action on the nerve terminals via purinergic receptors. Several papers highlight the phenomenon and explore the underlaying mechanisms of mast cell-induced modulation of the blood-brain barrier permeability. Thus, Kempuraj et al., ( focuses on the pathogenic stress as the initial trigger in development of neurodegenerative diseases. Specially, they propose the important role of the stress associated corticotropin-releasing hormone (CRH) in activation of mast cells ultimately leading to neuroinflammation. Tran et al., 2019Tran et al., ( provide novel mechanistic insights into mast cell-induced blood-brain barrier damage in cerebrovascular diseases via endoplasmic reticulum stress in the endothelium.In summary, this e-book presents the current state of knowledge about the involvement of mast cells in pain, itch, neuroinflammation and associated neurological disorders. This collection identifies treatable targets for the development of novel pharmacologic agents and approaches for the treatment of pain and neuro-inflammatory disorders.The Editorial is devoted to the memory of our colleague Stephen Skaper who passed away in 2018 soon after start of this project. Dr Skaper's contribution to the field of mast cells will continue to guide the field, and his contribution to the editorial efforts of this issue are highly appreciated. All other authors listed have made a substantial, direct and intellectual contribution to the Editorial and publication process.

Keywords: Mast Cells, Pain, itch, Neuroinflammation, neuro-immune synapse

Received: 28 Oct 2019; Accepted: 07 Nov 2019.

Copyright: © 2019 Giniatullin, Gupta and Theoharides. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Prof. Rashid Giniatullin, University of Eastern Finland, Kuopio, Finland,