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PO-85 | Alterations in gut microbiota and the endocannabinoid system in an animal model of chronic migraine

Società Italiana per lo studio delle Cefalee (SISC)

Confinia cephalalgica (Milano), 2025

Abstract

Background: The endocannabinoid system (ECs) with its receptors and ligands is a complex cell-signalling system widely present in the nervous system and in the gastrointestinal tract. The ECs regulates inflammatory responses and intestinal homeostasis through its interactions with the gut microbiota, ultimately influencing brain function both indirectly, via gut-derived circulating factors, and directly, through vagus nerve signalling. Increasing evidence points to a role for the ECs in chronic migraine. The aim of this study was to assess whether gut dysbiosis is associated with alterations in the ECs, both centrally and peripherally, in a chronic migraine-like animal model induced by repeated nitroglycerin (NTG) administration.

Methods: Adult male Sprague-Dawley rats were treated with NTG (5 mg/kg i.p.) or vehicle every two days over nine days (5 total injections). On day nine, four hours after the last administration of NTG or vehicle, rats were tested for migraine-like hyperalgesia (orofacial formalin test). The intestine and trigeminal ganglion were collected to assess the gene expression of ECs components using real-time PCR. Fecal 16S ribosomal RNA gene sequencing was used to assess alterations in the gut flora.

Results: Chronic NTG administration significantly increased face rubbing time during phase II of the orofacial formalin test, confirming the development of trigeminal hyperalgesia. Gut microbiota analysis revealed significant differences in beta-diversity…

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