Younis S, et al. - Researchers aimed to investigate the sildenafil- and calcitonin gene-related peptide (CGRP)-induced glutamate changes in both brainstem and thalamus via scanning 17 healthy participants with the human pharmacological proton (¹H) magnetic resonance spectroscopy (MRS) protocol (point-resolved spectroscopy pulse sequence, repetition time 3000 ms, echo time 37.6–38.3 ms) at baseline and twice (at 40 min and 140 min) after drug administration in this double-blind, placebo-controlled, randomized, double-dummy, three-way cross-over design. They noted transient sildenafil-induced glutamate change in the brainstem that possibly reflects increased excitability of the brainstem neurons. Brainstem or thalamic glutamate changes were not evident with CGRP, suggesting that it rather exerts its headache-inducing effects on the peripheral trigeminal pain pathways.