79: Dulaglutide Attenuates Chronic Migraine�Like Pain in Both Sexes: Toward Novel Preventive Strategies

Topic: Basic Science
Subtopic: Pain category (ICD-11), Chronic primary headache, , , Pharmacological interventions, Assessment and Measurement of Pain/Nociception, Behavioral studies, , , , , ,

Background and Aims: Chronic migraine (CM) is a highly disabling condition disproportionately affecting young women (1). Migraine frequently coexists with obesity, insulin resistance, and diabetes, which may increase disease burden (2). Agents with dual antinociceptive and metabolic properties represent a rational therapeutic avenue for CM. Liraglutide, a glucagon-like peptide-1 receptor agonist widely used in the treatment of type 2 diabetes and obesity, has recently demonstrated efficacy in CM in preclinical and clinical settings (3,4). We evaluated the antinociceptive efficacy and metabolic safety of dulaglutide compared with propranolol (reference drug) following repeated prophylactic administration in a nitroglycerin (NTG)-induced CM model in both sexes.

Methods: A chronic migraine-like state was induced by repeated, intermittent NTG administration in male and female C57BL/6 mice. Dulaglutide (30–300 µg/kg, every three days, s.c.) and propranolol (20 mg/kg/day, i.p.) were administered throughout the protocol. To assess the development of pain hypersensitivity and the antinociceptive effects of corresponding treatments, a battery of stimulus-evoked nociceptive tests was performed: basal and acute von Frey (mechanical stimulus), acetone (cold stimulus), and orofacial glutamate (chemical stimulus) tests. Body weight and glucose tolerance were monitored to assess metabolic safety. Data were analyzed using one-way/two-way repeated-measures ANOVA (Tukey’s post hoc test).

Results: Repeated intermittent NTG administration induced sustained stimulus-evoked pain hypersensitivity in both male and female mice (P < 0.01). Prophylactically administered dulaglutide dose-dependently attenuated the development of basal and acute mechanical, thermal, and chemical pain hypersensitivity in CM mice of both sexes (all P < 0.01), with the antinociceptive efficacy comparable to propranolol. ED₅₀ analysis indicated the greatest potency in the orofacial glutamate test, particularly in males. Dulaglutide did not significantly affect body weight or blood glucose levels (P > 0.05), whereas propranolol induced male-specific hyperglycemia (P < 0.05).

Conclusions: Dulaglutide attenuated chronic migraine-like pain in male and female CM mice with efficacy comparable to propranolol, the reference drug. Unlike propranolol, dulaglutide demonstrated a favourable metabolic safety profile without affecting body weight or glucose homeostasis in normal-weight, normoglycemic animals. These findings support the repurposing of dulaglutide as a preventive treatment for migraine, particularly in patients with cardiometabolic comorbidities. Further clinical studies are warranted to evaluate its efficacy and safety in this context.

References: 1. Steiner, T. J., Stovner, L. J., Jensen, R., Uluduz, D., Katsarava, Z., & Lifting The Burden: the Global Campaign against Headache. (2020). Migraine remains second among the world’s causes of disability, and first among young women: findings from GBD2019. The Journal of Headache and Pain, 21:137.
2. Rivera-Mancilla, E., Al-Hassany, L., Villalón, C.M., MaassenVanDenBrink, A. (2021). Metabolic Aspects of Migraine: Association With Obesity and Diabetes Mellitus. Frontiers in Neurology 12, 686398.
3. Jing, F., Zou, Q., Wang, Y., Cai, Z., Tang, Y. (2021). Activation of microglial GLP-1R in the trigeminal nucleus caudalis suppresses central sensitization of chronic migraine after recurrent nitroglycerin stimulation. The Journal of Headache and Pain, 22(1), 86.
4. Braca, S., Russo, C.V., Stornaiuolo, A., Cretella, G., Miele, A., Giannini, C., De Simone, R. (2025). Effectiveness and tolerability of liraglutide as add-on treatment in patients with obesity and high-frequency or chronic migraine: A prospective pilot study. Headache, 65(10), 1831–1838.

Presenting Author: Ana Micov
Submitting Author: Ana Micov

Senior Author: Ana Micov

IASP 2026 Global Year theme of Neuropathic Pain: No

• Katarina Sićović: MSc, PhD candidate - University of Belgrade, Faculty of Pharmacy
• Katarina Nastić: PhD, Teaching Assistant - University of Belgrade, Faculty of Pharmacy
• Uroš Pecikoza: PhD, Assistant Professor - University of Belgrade, Faculty of Pharmacy