Mast cell ‐neural interactions contribute to pain and itch
Summary 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.
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AbstractPurpose of reviewRecent studies demonstrate that normal human tissues accumulate substantial numbers of somatic mutations with aging, to levels comparable to their corresponding cancers. If mutations cause cancer, how do tissues avoid cancer when mutations are unavoidable?Recent findingsThe small intestines (SI) and colon accumulate similar numbers of replication errors, but SI adenocarcinoma is much rarer than colorectal cancer. Both the small and large intestines are subdivided into millions of small neighborhoods (crypts) that are maintained by small numbers of stem cells. To explain the SI cancer paradox, four ...