Migraine is a debilitating condition, however, the pharmacological effects on central nervous system networks following successful therapy is poorly understood. Defining this neurocircuitry is critical to our understanding of the disorder and for the development of anti-migraine drugs. Using an established inflammatory soup (IS) model of migraine-like pathophysiology (N=12) compared to sham synthetic interstitial fluid (SIF) migraine induction (N=12), our aim was to evaluate changes in network-level functional connectivity following sumatriptan-naproxen infusion in awake, conscious, rodents (Sprague-Dawley rats). Sumatriptan-naproxen infusion fMRI data was analyzed using an independent competent analysis approach. Whole brain analysis yielded significant between-group (IS vs. SIF) alterations in functional connectivity across the cerebellar, default mode, basal ganglia, autonomic, and salience networks. These results demonstrate the large-scale anti-migraine effects of sumatriptan-naproxen co-administration following dural sensitization.