Triptan-induced disruption of trigemino-cortical connectivity

TY - JOUR

T1 - Triptan-induced disruption of trigemino-cortical connectivity

AU - Kröger, Inga L

AU - May, Arne

N1 - © 2015 American Academy of Neurology.

PY - 2015/5/26

Y1 - 2015/5/26

N2 - OBJECTIVE: The 5-HT1B/D agonists (triptans) are specific headache medications that have no effect on pain as such. Although they are routinely used in the treatment of acute migraine attacks, the underlying mechanisms of action are still a matter of debate.METHODS: Forty-three healthy participants underwent fMRI while receiving trigemino-nociceptive stimulation and control stimuli in a standardized fMRI paradigm. Using a crossover, double-blind, placebo-controlled design, 21 participants (10 women, mean age 26.9, range 20-37 years) received sumatriptan and 22 participants (11 women, mean age 25.5, range 22-32 years) received acetylsalicylic acid (ASA). Administration of medication and saline was randomized between participants of each group resulting in half of the participants receiving saline and the other half receiving the respective medication during the first fMRI data acquisition.RESULTS: While mean pain intensity ratings did not differ significantly between control and medication nor between medications, we found a significant blood oxygen level-dependent signal increase in the trigeminal nuclei and the thalamus after sumatriptan treatment compared with placebo or ASA. In addition, we specifically looked for the pharmacologic modulation of functional coupling between trigeminal nuclei and higher brain areas, i.e., trigemino-cortical pathways, and found a strong coupling during the saline condition, which was altered by sumatriptan but not after ASA administration.CONCLUSION: These data suggest that a specific functional inhibition of trigemino-cortical projections is one of the reasons that triptans, unlike pain killers, act highly specifically on headache and migraine but not pain as such.

AB - OBJECTIVE: The 5-HT1B/D agonists (triptans) are specific headache medications that have no effect on pain as such. Although they are routinely used in the treatment of acute migraine attacks, the underlying mechanisms of action are still a matter of debate.METHODS: Forty-three healthy participants underwent fMRI while receiving trigemino-nociceptive stimulation and control stimuli in a standardized fMRI paradigm. Using a crossover, double-blind, placebo-controlled design, 21 participants (10 women, mean age 26.9, range 20-37 years) received sumatriptan and 22 participants (11 women, mean age 25.5, range 22-32 years) received acetylsalicylic acid (ASA). Administration of medication and saline was randomized between participants of each group resulting in half of the participants receiving saline and the other half receiving the respective medication during the first fMRI data acquisition.RESULTS: While mean pain intensity ratings did not differ significantly between control and medication nor between medications, we found a significant blood oxygen level-dependent signal increase in the trigeminal nuclei and the thalamus after sumatriptan treatment compared with placebo or ASA. In addition, we specifically looked for the pharmacologic modulation of functional coupling between trigeminal nuclei and higher brain areas, i.e., trigemino-cortical pathways, and found a strong coupling during the saline condition, which was altered by sumatriptan but not after ASA administration.CONCLUSION: These data suggest that a specific functional inhibition of trigemino-cortical projections is one of the reasons that triptans, unlike pain killers, act highly specifically on headache and migraine but not pain as such.

KW - Adult

KW - Anti-Inflammatory Agents, Non-Steroidal

KW - Aspirin

KW - Cerebral Cortex

KW - Double-Blind Method

KW - Female

KW - Humans

KW - Magnetic Resonance Imaging

KW - Male

KW - Neural Pathways

KW - Nociception

KW - Serotonin 5-HT1 Receptor Agonists

KW - Sodium Chloride

KW - Sumatriptan

KW - Thalamus

KW - Trigeminal Nuclei

KW - Young Adult

U2 - 10.1212/WNL.0000000000001610

DO - 10.1212/WNL.0000000000001610

M3 - SCORING: Journal article

C2 - 25948722

VL - 84

SP - 2124

EP - 2131

JO - NEUROLOGY

JF - NEUROLOGY

SN - 0028-3878

IS - 21

ER -