Involvement of Mast Cells in the Pathophysiology of Pain

Abstract

Mast cells (MCs) are immune cells and are widely distributed throughout the body. MCs are not only classically viewed as effector cells of some allergic diseases but also participate in host defense, innate and acquired immunity, homeostatic responses, and immunoregulation. Mounting evidence indicates that activation of MCs releasing numerous vasoactive and inflammatory mediators has effects on the nervous system and has been involved in different pain conditions. Here, we review the latest advances made about the implication of MCs in pain. Possible cellular and molecular mechanisms regarding the crosstalk between MC and the nervous system in the initiation and maintenance of pain are also discussed.

Keywords: hyperalgesia; immunoregulation; inflammation; mast cells; pain.

Figure 1

Illustration outlining the mast cells (MCs) differentiation trajectories. Mast cells, lymphocytes, and myeloid cells are derived from pluripotent hematopoietic progenitors in the bone marrow. Unlike basophils that attain their maturity in the circulation, mast cell precursors circulate in the bloodstream as immature cells and are transited out to the peripheral tissues where they mature under the influence of growth factors.

Figure 2

(A) Schematic illustration of mast cell involvement in peripheral sensitization in the terminals of nociceptive primary afferents. Mast cell degranulation induces the production of proinflammatory mediators [e.g., 5-HT, TNF, nerve growth factor (NGF), histamine, tryptase], resulting in nociceptive neurons release vasoactive neuropeptides, which in turn, leads to the recruitment of immune cells, including mast cells, macrophage, neutrophil, T cell, etc. This leads to the possibility of positive feedback loop, which could lead to chronic pain. (B) Molecular mechanisms of central sensitization induced by mast cells degranulation in first-order excitatory synapses, where communications between neuronal and non-neuronal cells occur. Central terminals of nociceptors release inflammatory factors that activate the second-order neurons and non-neuronal cells including mast cells, which induces neuronal activation via producing proinflammatory cytokines and chemokines [e.g., TNF, interleukins (IL)-1β, CCL2, CXCL1], and granular components, such as 5-HT and serotonin.