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Cerebrovascular and behavioral changes in the nitroglycerin mouse model of migraine

Rebecca Ortiz, Jordan Johnson, Dmitri Yousef-Yengej, Guido C. Faas, Maria C. Jordan, Kenneth P. Roos, Andrew Charles, Sinifunanya E. Nwaobi

The Journal of Headache and Pain, 2026

24 participants

Abstract

Abstract Background Nitroglycerin (NTG) is an established human migraine trigger, and administration in rodents is a commonly used migraine model. While the sensory sensitivity that occurs in response to NTG in rodents has been extensively studied, other physiological and behavioral responses have not been well characterized. We investigated the cerebrovascular, sleep, and behavioral effects of repeated NTG exposure in freely behaving mice using a minimally invasive microelectronic system. Methods A minimally invasive micro-electronic recording system was used to measure cerebral blood volume (CBV), head movement, and sleep including rapid eye movement (REM) and non-REM (NREM) sleep in freely behaving male and female C57BL/6J mice. Following a 10-day baseline period, 10 mg/kg NTG or vehicle control were administered by intraperitoneal injection every other day as a model of chronic migraine. Results NTG administration resulted in a biphasic change in CBV with an initial acute increase over 15 minutes, followed by a significant and prolonged reduction below baseline, lasting for 2 hours (mixed ANOVA, saline vs NTG X Injection Time, CBV: F (38,836) =9.767, p < 0.001, N = 22). Concurrent telemetry monitoring of blood pressure and heart rate demonstrated CBV reductions persisted despite normalization of systemic blood BP and heart rate. NTG administration also resulted in an acute reduction in animal movement in the 3 hours following administration (mixed ANOVA, saline vs NTG X…

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