Central effects of acetylsalicylic acid on trigeminal-nociceptive stimuli

Abstract

Background: Acetylsalicylic acid is one of the most used analgesics to treat an acute migraine attack. Next to the inhibitory effects on peripheral prostaglandin synthesis, central mechanisms of action have also been discussed.

Methods: Using a standardized model for trigeminal-nociceptive stimulation during fMRI scanning, we investigated the effect of acetylsalicylic acid on acute pain compared to saline in 22 healthy volunteers in a double-blind within-subject design. Painful stimulation was applied using gaseous ammonia and presented in a pseudo-randomized order with several control stimuli. All participants were instructed to rate the intensity and unpleasantness of every stimulus on a VAS scale. Based on previous results, we hypothesized to find an effect of ASA on central pain processing structures like the ACC, SI and SII as well as the trigeminal nuclei and the hypothalamus.

Results: Even though we did not find any differences in pain ratings between saline and ASA, we observed decreased BOLD signal changes in response to trigemino-nociceptive stimulation in the ACC and SII after administration of ASA compared to saline. This finding is in line with earlier imaging results investigating the effect of ASA on acute pain. Contrary to earlier findings from animal studies, we could not find an effect of ASA on the trigeminal nuclei in the brainstem or within the hypothalamic area.

Conclusion: Taken together our study replicates earlier findings of an attenuating effect of ASA on pain processing structures, which adds further evidence to a possibly central mechanism of action of ASA.

Figure 1

BOLD signal intensity during painful stimulation: Saline > ASA. Increased BOLD signal intensity in the anterior cingulate cortex (left) and secondary somatosensory cortex (right) during nociceptive input (ammonia > air puffs) after saline treatment compared to ASA condition. Visualization threshold is set to p < 0.001 (uncorrected). Bold activation is projected onto a MNI152_T1 brain template (FSL). Color scales show T values of individual voxels.