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.

Nociceptor Sensory Neuron–Immune Interactions in Pain and Inflammation

“…Electron microscopy indicates close association of nociceptor nerve terminals with mast cells in mucosal tissues. Upon activation, mast cells degranulate and release cytokines (IL-5, TNFα, IL-6, IL-1β), 5-HT, histamine, and nerve growth factor (NGF), which act through receptors on nociceptors leading to pain sensitization [5–7]. Besides their contribution to pain during acute inflammation [8], mast cells accumulate in chronic inflammatory conditions and contribute to the chronicity of pain [9].…”

“…Nociceptor neurons may drive lung inflammation through their release of the neuropeptide VIP, which acts on the VPAC2 receptor expressed by Type 2 innate lymphoid cells (ILC2) to induce IL-5 production [42] (Figure 3d). Neuropeptides also potentiate degranulation of mast cells, key mediators of allergic inflammation [5,96]. Thus, silencing neurons may be a strategy to treat asthmatic lung inflammation.…”

Rats bred for low and high running capacity display alterations in peripheral tissues and nerves relevant to neuropathy and pain

“…Similar to Langerhans cells, mast cells play a significant role in innate and adaptive immunity; however, they modulate neuropeptides involved in sensory processing and signaling (Aich, Afrin, & Gupta, 2015; Madva & Granstein, 2013). Mast cells have a well‐established neuroimmune response through the reaction to inflammatory signaling and subsequent synthesis and release of neurotrophins highlighting an important molecular marker of peripheral nerve inflammatory response (Bienenstock et al., 1987; Leon et al., 1994).…”

Could Perioperative Opioid Use Increase the Risk of Cancer Progression and Metastases?

“…53 Mast cells have been implicated in angiogenesis and tumor progression via their recruitment and the effects of mediators released into the tumor microenvironment. 54 Morphine is known to stimulate mast cell degranulation.…”

“…55 Upon activation, mast cells release, among other mediators, the neuropeptide substance P (SP). 53 The activity of SP is mediated via tachykinin 1 (NK-1) receptor. 56 Tumor cells overexpress NK-1 receptors, and SP has been shown to enhance tumor cell proliferation in different types of cancer cell lines and cancer cell migration in pancreatic cancer via NK-1 receptor.…”