Mast Cells in the Autonomic Nervous System and Potential Role in Disorders with Dysautonomia and Neuroinflammation 2023, Theoharides et al

Abstract
Mast cells (MC) are ubiquitous in the body and are critical for allergic diseases, but also in immunity and inflammation, as well as potential involvement in the pathophysiology of dysautonomias and neuroinflammatory disorders. MC are located perivascularly close to nerve endings and sites such as the carotid bodies, heart, hypothalamus, the pineal and the adrenal glands that would allow them to regulate, but also be affected by the autonomic nervous system (ANS).

MC are stimulated not only by allergens, but also many other triggers including some from the ANS that can affect MC release of neurosensitizing, proinflammatory and vasoactive mediators. Hence MC may be able to regulate homeostatic functions that appear to be dysfunctional in many conditions, such as postural orthostatic hypertension syndrome (POTS), autism spectrum disorder (ASD), myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and Long-COVID syndrome.

The evidence indicates that there is a possible association between these conditions and diseases associated with mast cell activation, There is no effective treatment for any form of these conditions other than minimizing symptoms. Given the many ways MC could be activated and the numerous mediators released, it would be important to develop ways to inhibit stimulation of MC and the release of ANS-relevant mediators.

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https://www.annallergy.org/article/S1081-1206(23)01397-2/fulltext