The lecture below makes it understandable, why a mast cell modulator as palmitoylethanolamide can be used to treat chronic pain, inflammation and depression:
Mast cells derive from hematopoietic stem cells and circulate as immature progenitors; maturation occurs upon reaching their destination tissue (Galli et al., 2005; Galli and Tsai, 2008). Mast cells are characterized by a high density of cytoplasmic granules which undergo partial or complete degranulation in response to a wide range of immunological and non-immunological stimuli. These granules contain plethora of mediators, including histamine, heparin, serotonin, chemotactic factors and various proteases such as peroxidase, tryptase, chymase, carboxidase, and beta-glucuronidase (Frenzel & Hermine, 2012). Mast cells are unique in that they are the only cell type that stores pre-formed tumor necrosis factor alpha (TNF-α) in secretory granules (Olszewski et al., 2007), which positions them as early responders in acute inflammatory responses (Jim et al., 2009). Moreover, activated mast cells are capable of elaborating secondary mediators such as prostaglandins, leukotrienes, numerous cytokines (e.g. interleukins (IL)-1, -3, -4, -5, -6, -10, -4 and -17, as well as transforming growth factor beta and nerve growth factor (Leon et al., 1994; Halova et al., 2012).
By synthesizing and releasing diverse types of inflammatory mediators, mast cells may provoke pathophysiological changes in various organs and systems, leading to intersystemic homeostasis imbalance and development of pathological conditions often associated with persistent inflammation and chronic or neuropathic pain (Ren & Dubner, 2010; Dai & Korthuis, 2011; Anand et al., 2012).
Graziottin A. Fusco M. Mast cells in chronic inflammation, pain and depression. Full paper under link: