Mast Cell-Mediated Mechanisms of Nociception

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.

Keywords: cancer; cytokines; hyperalgesia; inflammation; mast cells; migraine; pain; sickle cell disease; substance P; tryptase.

Figure 1

Mast cell-associated disease-specific pain syndromes, mast cell activation and its common activators: ATP (Adenosine tri-phosphate), chemokines, C3α, C5α (Complement 3α, 5α), estrogens, immunoglobins (IgE, IgG₁), CGRP (calcitonin gene-related peptides), SP (substance P), CRH (corticotropin-releasing hormone), NGF (nerve growth factor), SCF (stem cell growth factor), trypsin, tryptase, venoms, vasoactive intestinal peptides.