Glyceryl Trinitrate (GTN) Migraine Model

Migraine is a highly prevalent and disabling condition, and intravenous glyceryl trinitrate (GTN), a nitric oxide (NO) donor, is a well-established human provocation model, reliably triggering migraine-like headache in susceptible individuals.

Intraperitoneal GTN administration in rats reproduces this trigeminovascular activation: NO release drives neuronal activation in the trigeminal nucleus caudalis, dural neurogenic inflammation, and CGRP release, closely mirroring the pathophysiology of a spontaneous migraine attack.

In rats, GTN induces periorbital and hindpaw mechanical allodynia, assessed by von Frey filaments, alongside spontaneous pain-like behaviors — a phenotype considered the extracephalic and craniofacial correlate of migraine-associated allodynia reported by patients.

The model’s specificity and translational validity are confirmed by its responsiveness to sumatriptan, the prototypic anti-migraine therapeutic, which attenuates both the behavioral and neuronal (c-Fos) hallmarks of GTN-induced activation.

This pharmacological concordance with clinically effective treatments makes the GTN model a key preclinical tool for screening novel acute and prophylactic anti-migraine compounds.