Topiramate Inhibits Capsaicin-Induced Mast Cell Degranulation and CGRP Release in Rat Dura Mater.

Autor: Costa RF; Postgraduate Program in Biology Science, Federal University of Pernambuco (UFPE), Recife 50670-901, Brazil., Rosas EP; Immunopathology Laboratory (LIKA), Federal University of Pernambuco (UFPE), Recife 50670-901, Brazil., Paz ST; Anatomy Department, Federal University of Pernambuco (UFPE), Recife 50670-901, Brazil., Freitas MFL; Patology Department, Federal University of Pernambuco (UFPE), Recife 50670-901, Brazil., Souza SL; Neuropsychiatry and Behavioral Sciences Laboratory, Federal University of Pernambuco (UFPE), Recife 50670-901, Brazil., Andrade JR; Immunopathology Laboratory (LIKA), Federal University of Pernambuco (UFPE), Recife 50670-901, Brazil., Oliveira DA; Physiotherapy Department, Federal University of Pernambuco (UFPE), Recife 50670-901, Brazil., Jansen-Olesen I; Neurology Department, Danish Headache Center, Copenhagen University Hospital-Rigshospitalet, 2600 Copenhagen, Denmark., Christensen SL; Neurology Department, Danish Headache Center, Copenhagen University Hospital-Rigshospitalet, 2600 Copenhagen, Denmark.; Anesthesia Department, Critical Care and Pain Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115, USA.; Department of Clinical Medicine, University of Copenhagen, 2200 Copenhagen, Denmark., Valença MM; Neurosurgery Unit, Federal University of Pernambuco (UFPE), Recife 50670-901, Brazil.
Jazyk: angličtina
Zdroj: Brain sciences [Brain Sci] 2024 Oct 27; Vol. 14 (11). Date of Electronic Publication: 2024 Oct 27.
DOI: 10.3390/brainsci14111070
Abstrakt: Background/objectives: Migraine is a disease that stands out for its high prevalence and socioeconomic costs. It involves the entire trigeminovascular system, the signaling substances, and their targets. However, the role of meningeal mast cells in migraine is still unclear. To better understand one of the components of neurogenic inflammation underlying migraine pathophysiology, we developed an in vivo rat model in which the dura mater was exposed bilaterally to investigate the influence of topiramate on capsaicin-induced mast cell degranulation and CGRP release from dura mater.
Methods: On the day of the experiment, rats were anesthetized, and a craniectomy was performed on each parietal bone. Test substances were applied in situ over the dura mater using the right and left sides of the dura mater for the test and control, respectively. After exposure, the dura mater was processed for mast cell staining and counting. Using this setup, the effect of capsaicin (10 -3 M) was evaluated in rats of both sexes, and subsequently the effect of in situ (10 -3 M, 20 µL) and (20 mg/kg/day for 10 days) topiramate treatment on mast cell degranulation and CGRP release were evaluated.
Results: In both female and male rats, there was a greater amount of degranulated mast cells in the side stimulated by capsaicin compared to the control side in both females (18 ± 3% vs. 74 ± 3%; p = 0.016) and males (28 ± 2% vs. 74 ± 3%, p = 0.016). In the group treated with topiramate for 10 days prior to the experiments, capsaicin did not induce mast cell degranulation (control 20 ± 1% vs. capsaicin 22 ± 1%, p = 0.375) in contrast to animals treated for 10 days with gavage control (control 25 ± 1% vs. capsaicin 76 ± 1%, p = 0.016). Topiramate applied in situ concomitant with capsaicin did not protect the mast cells from degranulation in response to capsaicin (38 ± 2% vs. 44 ± 1%, p = 0.016). There was a significant reduction in CGRP release from the dura mater in the group treated with topiramate for 10 days compared to the control.
Conclusions: This study demonstrates a novel experimental model wherein systemic administration of topiramate is observed to modulate the impact of capsaicin on meningeal mast cell degranulation.
Databáze: MEDLINE
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