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SHR Neuro Krebs Kardio Lipid Stoffw Microb

Starkl, P; Jonsson, G; Artner, T; Turnes, BL; Gail, LM; Oliveira, T; Jain, A; Serhan, N; Stejskal, K; Lakovits, K; Hladik, A; An, M; Channon, KM; Kim, H; Köcher, T; Weninger, W; Stary, G; Knapp, S; Klang, V; Gaudenzio, N; Woolf, CJ; Tikoo, S; Jain, R; Penninger, JM; Cronin, SJF.
Mast cell-derived BH4 and serotonin are critical mediators of postoperative pain.
Sci Immunol. 2024; 9(98):eadh0545 Doi: 10.1126/sciimmunol.adh0545
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Autor*innen der Med Uni Graz:
Jonsson Gustav
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Abstract:
Postoperative pain affects most patients after major surgery and can transition to chronic pain. The considerable side effects and limited efficacy of current treatments underline the need for new therapeutic options. We observed increased amounts of the metabolites BH4 and serotonin after skin injury. Mast cells were primary postoperative sources of Gch1, the rate-limiting enzyme in BH4 synthesis, itself an obligate cofactor in serotonin production by tryptophan hydroxylase (Tph1). Mice deficient in mast cells or in mast cell-specific Gch1 or Tph1 showed drastically decreased postoperative pain. We found that injury induced the nociceptive neuropeptide substance P, mast cell degranulation, and granule nerve colocalization. Substance P triggered serotonin release in mouse and human mast cells, and substance P receptor blockade substantially ameliorated pain hypersensitivity. Our findings highlight the importance of mast cells at the neuroimmune interface and substance P-driven mast cell BH4 and serotonin production as a therapeutic target for postoperative pain treatment.
Find related publications in this database (using NLM MeSH Indexing)
Mast Cells - immunology
Serotonin - metabolism
Animals - administration & dosage
Pain, Postoperative - immunology
Mice - administration & dosage
Humans - administration & dosage
Mice, Inbred C57BL - administration & dosage
Substance P - metabolism
Male - administration & dosage
Mice, Knockout - administration & dosage
Tryptophan Hydroxylase - metabolism

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