P1.42. SEX-DEPENDENT NEURONAL ACTIVATION AND BEHAVIOURAL DYSFUNCTION CAUSED BY NTG-INDUCED MIGRAINE IS REVERSED BY NOP RECEPTOR AGONIST
Akanksha Mudgal1,2, Diana Pietrzak-Mitura1, Olga Wronikowska-Denysiuk1, Lawrence Toll2, Akihiko Ozawa2, Katarzyna Targowska-Duda1,2
1 Department of Biopharmacy, Medical University of Lublin, Poland
2 Department of Biomedical Science, Florida Atlantic University, Boca Raton, FL, USA
INTRODUCTION: Migraine is a debilitating neurological disorder associated not only with sensory disturbances but also with impairments in social behavior. However, the neural mechanisms underlying migraine-associated social dysfunction remain poorly understood.
AIM(S): This study aimed to identify specific brain regions contributing to migraine induced pain and social impairments and to investigate potential sex-dependent differences.
METHOD(S): Migraine-like symptoms were induced using nitroglycerin (NTG) in TRAP2/Ai9 transgenic mice. Neuronal activation was assessed in brain regions associated with pain and social behavior. Behavioral analyses included the three-chamber social novelty test and von Frey assay for mechanical allodynia. To assess therapeutic potential, the nociceptin/orphanin FQ peptide (NOP) receptor agonist Ro 64-6198 was administered.
RESULTS: NTG induced significant neuronal activation in the anterior cingulate cortex, amygdala, hippocampus, hypothalamus, and periaqueductal gray in female mice, and in the trigeminal nucleus caudalis in both sexes (p < 0.05). Behaviorally, NTG led to social avoidance, reflected by increased time spent in the neutral chamber (p = 0.0003). Male mice showed decreased direct contact with both familiar (p < 0.05) and non-familiar (p = 0.0048) mice, whereas female mice displayed reduced time in the chamber with the non-familiar mouse (p < 0.05). NTG also induced robust mechanical allodynia. Administration of Ro 64-6198 reversed both the allodynia and social deficits (p < 0.0001 in males; p = 0.0092 in females) and significantly reduced NTG-induced neuronal activation (p < 0.0001 in males; at least p < 0.05 in females).
CONCLUSIONS: These findings highlight sex-dependent neural and behavioral alterations underlying migraine-associated social dysfunction. Brain regions implicated in both pain and social behavior mediate these effects, and NOP receptor activation represents a promising therapeutic strategy extending beyond pain relief.
FINANCIAL SUPPORT: This work was supported by the grant from the Polish National Science Center (SONATA BIS 11 funding 2021/42/E/NZ7/00191) to KT-D.