STUDY OF THE EFFECTS OF RIMEGEPANT IN A MURINE MODEL OF ENDOMETRIOSIS AND MIGRAINE COMORBIDITY

Endometriosis (EM) is a painful condition which is frequently associated with comorbidities, including migraine, which occurs in EM patients at twice the rate observed in healthy women. This study was aimed to test the efficacy of Rimegepant, a selective antagonist of the calcitonin gene related peptide (CGRP) receptor, in targeting both EM and migraine signs in a murine model of this comorbidity. To induce EM, we injected mice with uterine fragments from donor mice. Sham mice were injected with PBS. To mimic migraine, glyceryl trinitrate (GTN) (0.1, 1 or 10 mg/kg) was injected every two weeks, starting at 14 days post-implantation (DPI). EM-like and migraine-like behaviors were assessed every 2 weeks up to 57 DPI. As EM signs, abdominal mechanical allodynia (AMA) and spontaneous pain-like behaviors were assessed. As a hallmark of migraine, periorbital mechanical allodynia (PMA) was measured. Starting at 14 DPI, EM mice exhibited increased AMA and increased spontaneous pain-like behavior compared to sham controls. Additionally, EM mice showed susceptibility to GTN 0.1 and 1 mg/kg, while sham mice displayed reduced periorbital mechanical thresholds only in response to GTN 10 mg/kg. Two clinically available drugs used for EM treatment (letrozole, 5 mg/kg, and danazol 35 mg/kg) were injected s.c. daily starting at 30 DPI. These drugs partially reduced EM signs but showed no efficacy on migraine signs. Finally, our preliminary data suggest that Rimegepant (1, 10 or 30 mg/Kg) exhibits efficacy in reducing both EM and migraine signs in a dose-dependent manner.