Central effects of acetylsalicylic acid on trigeminal-nociceptive stimuli

Abstract

BackgroundAcetylsalicylic 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.MethodsUsing 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.ResultsEven 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.ConclusionTaken 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.

Brain natriuretic peptide suppresses pain induced by BmK I, a sodium channel-specific modulator, in rats

“…Therefore, BNP secreted from nociceptive afferent neurons might be an endogenous analgesic molecule for BmK I-induced inflammatory pain. Considering the functional expression of BNP/NPRA signal system in both DRG and TG neurons, the activation of BNP signaling pathway might have a broad prospect in recovering chronic pain conditions including somatic pain and migraine [ 22 – 24 ].

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Abstracts and Citations

“…Conclusion: These data suggest that a specific functional inhibition of trigemino‐cortical projections is one of the reasons that triptans, unlike painkillers, act highly specifically on headache and migraine but not pain as such.

Comments: Continuing with hot off the press triptan issues in this publication, we find an extension of the pharmacological imaging work of these two researchers. In their first referenced article they wrote, ‘Imaging techniques give us the opportunity to gain a better understanding of drug processes in the central nervous system and help to understand where drugs reveal their therapeutic effect. While some substances work on the emotional‐affective component of pain, others modulate sensory‐discriminative pain pathways.” Next they reported their study of ASA in 22 healthy controls given a painful gaseous ammonia stimulus.

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“…While some substances work on the emotional‐affective component of pain, others modulate sensory‐discriminative pain pathways.” Next they reported their study of ASA in 22 healthy controls given a painful gaseous ammonia stimulus. “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.” They concluded that ASA had an attenuating effect on pain processing centers adding to the possibility of a central mechanism. Now they report a strong functional coupling between trigeminal nuclei and higher brain areas altered by sumatriptan but not ASA suggesting a specific functional inhibition of trigemino‐cortical projections as one of the reasons triptans act specific to headache but not pain in general.…”

“…“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.” They concluded that ASA had an attenuating effect on pain processing centers adding to the possibility of a central mechanism. Now they report a strong functional coupling between trigeminal nuclei and higher brain areas altered by sumatriptan but not ASA suggesting a specific functional inhibition of trigemino‐cortical projections as one of the reasons triptans act specific to headache but not pain in general. PJ Goadsby provides editorial comment which is brief and worth reading in its entirety.…”

“…“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.” They concluded that ASA had an attenuating effect on pain processing centers adding to the possibility of a central mechanism. …”