{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T16:03:50Z","timestamp":1791821030103,"version":"4.3.4"},"reference-count":195,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2026,4,4]],"date-time":"2026-04-04T00:00:00Z","timestamp":1775260800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Mast cells, characterized by a broad repertoire of surface receptors, are increasingly recognized for activation pathways extending beyond the classical IgE\/Fc\u03b5RI axis, particularly in the context of neurogenic inflammation. Substance P (SP), a neuropeptide of the tachykinin family, is a potent activator of mast cells, inducing the release of histamine, cytokines, and other inflammatory mediators. Through complex bidirectional communication, mast cells and SP play a pivotal role in neuro\u2013immune interactions. This narrative review provides an updated overview of mast cell\u2013SP crosstalk, with a focus on underlying molecular mechanisms, receptor-mediated signaling pathways, and their contribution to pathophysiological processes. In addition, we aim to reinterpret established clinical models within the spectrum of pseudoallergic conditions and to explore innovative, etiology-driven therapeutic strategies. Finally, we discuss future perspectives and highlight the need for robust translational models to support clinical and pharmacological research.<\/jats:p>","DOI":"10.3390\/biom16040539","type":"journal-article","created":{"date-parts":[[2026,4,6]],"date-time":"2026-04-06T04:10:27Z","timestamp":1775448627000},"page":"539","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Mast Cells and Substance P: Neuroinflammatory Loops at the Molecular and Translational Clinical Levels"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0452-3282","authenticated-orcid":false,"given":"Ernesto","family":"Aitella","sequence":"first","affiliation":[{"name":"Department of Life, Health and Environmental Sciences, University of L\u2019Aquila, 67100 L\u2019Aquila, Italy"},{"name":"Allergy and Clinical Immunology Unit, Center for the Diagnosis and Treatment of Osteoporosis, Azienda Unit\u00e0 Sanitaria Locale 04 Teramo, 64100 Teramo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marilena","family":"Bruno","sequence":"additional","affiliation":[{"name":"Department of Life, Health and Environmental Sciences, University of L\u2019Aquila, 67100 L\u2019Aquila, Italy"},{"name":"Allergy and Clinical Immunology Unit, Center for the Diagnosis and Treatment of Osteoporosis, Azienda Unit\u00e0 Sanitaria Locale 04 Teramo, 64100 Teramo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-7891-0463","authenticated-orcid":false,"given":"Gianluca","family":"Azzellino","sequence":"additional","affiliation":[{"name":"Department of Life, Health and Environmental Sciences, University of L\u2019Aquila, 67100 L\u2019Aquila, Italy"},{"name":"Complex Operational Unit, Adriatic District Area, Azienda Unit\u00e0 Sanitaria Locale 04 Teramo, 64100 Teramo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4253-1312","authenticated-orcid":false,"given":"Massimo","family":"De Martinis","sequence":"additional","affiliation":[{"name":"Department of Life, Health and Environmental Sciences, University of L\u2019Aquila, 67100 L\u2019Aquila, Italy"},{"name":"Long-Term Care Unit, \u201cMaria SS. dello Splendore\u201d Hospital, Azienda Unit\u00e0 Sanitaria Locale 04 Teramo, 64021 Teramo, Italy"},{"name":"UniCamillus-Saint Camillus International University of Health Sciences, 00131 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1841-2807","authenticated-orcid":false,"given":"Lia","family":"Ginaldi","sequence":"additional","affiliation":[{"name":"Department of Life, Health and Environmental Sciences, University of L\u2019Aquila, 67100 L\u2019Aquila, Italy"},{"name":"Allergy and Clinical Immunology Unit, Center for the Diagnosis and Treatment of Osteoporosis, Azienda Unit\u00e0 Sanitaria Locale 04 Teramo, 64100 Teramo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5807-6601","authenticated-orcid":false,"given":"Ciro","family":"Romano","sequence":"additional","affiliation":[{"name":"Clinical Immunology Outpatient Clinic, Division of Internal Medicine, Department of Advanced Medical and Surgical Sciences, \u201cLuigi Vanvitelli\u201d University of Campania, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"693","DOI":"10.1038\/nm.2755","article-title":"IgE and Mast Cells in Allergic Disease","volume":"18","author":"Galli","year":"2012","journal-title":"Nat. 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