The Histamine H
Autor: | Laura, Micheli, Mariaconcetta, Durante, Elena, Lucarini, Silvia, Sgambellone, Laura, Lucarini, Lorenzo, Di Cesare Mannelli, Carla, Ghelardini, Emanuela, Masini |
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Rok vydání: | 2021 |
Předmět: |
CD4-Positive T-Lymphocytes
neuropathic pain Adenosine Receptor Adenosine A3 interleukin-10 Thiourea H4R−/− mice Guanidines Article CD4+ T cells Interleukin-10 Disease Models Animal Mice Gene Expression Regulation Adenosine A3 Receptor Agonists Animals Humans Neuralgia H4R A3AR chronic constriction injury Receptors Histamine H4 allodynia |
Zdroj: | Biomolecules |
ISSN: | 2218-273X |
Popis: | A3 adenosine receptor (A3AR) agonists have emerged as potent relievers of neuropathic pain by a T cell-mediated production of IL-10. The H4 histamine receptor (H4R), also implicated in pain modulation, is expressed on T cells playing a preeminent role in its activation and release of IL-10. To improve the therapeutic opportunities, this study aimed to verify the hypothesis of a possible cross-talk between A3AR and H4R in the resolution of neuropathic pain. In the mouse model of Chronic Constriction Injury (CCI), the acute intraperitoneal co-administration of the A3AR agonist IB-MECA (0.5 mg/kg) and the H4R agonist VUF 8430 (10 mg/kg), were additive in counteracting mechano-allodynia increasing IL-10 plasma levels. In H4R−/− mice, IB-MECA activity was reduced, lower pain relief and lower modulation of plasma IL-1β, TNF-α, IL-6 and IL-10 were shown. The complete anti-allodynia effect of IB-MECA in H4R−/− mice was restored after intravenous administration of CD4+ T cells obtained from naïve wild type mice. In conclusion, a role of the histaminergic system in the mechanism of A3AR-mediated neuropathic pain relief was suggested highlighting the driving force evoked by CD4+ T cells throughout IL-10 up-regulation. |
Databáze: | OpenAIRE |
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