Mast cells are best recognized for their role in allergy and anaphylaxis, but increasing evidence supports their role in neurogenic inflammation leading to pain and itch. Mast cells act as a “power house” by releasing algogenic and pruritogenic mediators, which initiate a reciprocal communication with specific nociceptors on sensory nerve fibers. Consequently, nerve fibers release inflammatory and vasoactive neuropeptides, which in turn activate mast cells in a feedback mechanism, thus promoting a vicious cycle of mast cell and nociceptor activation leading to neurogenic inflammation and pain/pruritus. Mechanisms underlying mast cell differentiation, activation, and intercellular interactions with inflammatory, vascular, and neural systems are deeply influenced by their microenvironment, imparting enormous heterogeneity and complexity in understanding their contribution to pain and pruritus. Neurogenic inflammation is central to both pain and pruritus, but specific mediators released by mast cells to promote this process may vary depending upon their location, stimuli, underlying pathology, gender, and species. Therefore, in this review, we present the contribution of mast cells in pathological conditions, including distressing pruritus exacerbated by psychologic stress and experienced by the majority of patients with psoriasis and atopic dermatitis and in different pain syndromes due to mastocytosis, sickle cell disease, and cancer.
Bibliographical noteFunding Information:
Authors extremely thank Huy Tran and Aithanh Nguyen for preparing the illustrations; Huy Tran and Julia Nguyen for Laser Scanning Confocal Microscopy of sickle mouse skin for mast cell activation with nerves and vascular structures; Huy Tran for assisting with manuscript preparation; Michael J. Franklin for editorial suggestions and manuscript editing; and Drs Samir Ballas, Tom Coates, Deepika Darbari, Greg Kato, Elizabeth Klings, and Caterina Minniti on consultation for pain and itch in sickle cell disease. This effort has been funded by NIH grants UO1 HL117664 and R01HL103773 to K. G. The Cancer Center of Eastern Finland and the VTR-funding of Kuopio University Hospital are acknowledged for providing support to I. T. H. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
- atopic dermatitis
- mast cell
- neurogenic inflammation
- sickle cell disease