Abstract
Mast cells are tissue-resident immune cells that release immuno-modulators, chemo-attractants, vasoactive compounds, neuropeptides and growth factors in response to allergens and pathogens constituting a first line of host defense. The neuroimmune interface of immune cells modulating synaptic responses has been of increasing interest, and mast cells have been proposed as key players in orchestrating inflammation-associated pain pathobiology due to their proximity to both vasculature and nerve fibers. Molecular underpinnings of mast cell-mediated pain can be disease-specific. Understanding such mechanisms is critical for developing disease-specific targeted therapeutics to improve analgesic outcomes. We review molecular mechanisms that may contribute to nociception in a disease-specific manner.
Highlights
For nearly 150 years since the discovery of mast cells (MC) in 1863, first in frog tissue [1] and shortly thereafter in human tissue [2], the only Mast cells (MCs) disease known beyond allergic phenomena was the rare neoplastic mastocytosis in its various forms
MCs can interact with the nervous system bi-directionally, as MC-derived mediators such as tryptase and histamine lead to release of neuropeptides, e.g., substance P (SP) and calcitonin gene-related peptide (CGRP) from the proximal nerve endings [29], and subsequently SP can further activate MCs [30]
Increased MC counts in proximity of neural system [31,32] and abnormalities in nerve fiber structure have been correlated with nerve growth factor (NGF), a MC-derived and nerve fiber-derived mediator which is a bidirectional source of hyperalgesia [33]
Summary
For nearly 150 years since the discovery of mast cells (MC) in 1863, first in frog tissue [1] and shortly thereafter in human tissue [2], the only MC disease known beyond allergic phenomena was the rare neoplastic mastocytosis in its various forms (cutaneous [3,4,5] and systemic [6,7]). Interaction between immune and neural system, known as the neuroimmune interface, has been of immense interest for understanding the molecular mechanisms of peripheral and central sensitization underlying chronic pain [17]. MCs reside in all tissues, predominantly those interacting with the external environment such as intestines, airways and skin [20], as well as in the dura mater at the spinal cord level and in the meninges of the brain [22]. Their proximity to the external environment enables MCs to be first responders to external pathogen and allergen exposure. Dysregulation of MC activation contributes to sustained inflammation and altered homeostatic imbalance via pro-inflammatory MC mediators which lead and/or contribute to diverse pathological conditions including, Alzheimer’s disease, anxiety, multiple sclerosis, rheumatoid arthritis, bladder pain syndrome, atherosclerosis, pulmonary hypertension, ischemia-reperfusion injury, irritable bowel syndrome, male infertility, obesity, diabetes mellitus and nociception [28]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
