Abstract
To explore the functional reorganization of the pain processing network during trigeminal heat stimulation (THS) after 60 days of external trigeminal neurostimulation (eTNS) in migraine without aura (MwoA) patients between attacks. Using whole-brain BOLD-fMRI, functional response to THS at two different intensities (41 and 51°C) was investigated interictally in 16 adults MwoA patients before and after eTNS with the Cefaly® device. We calculated the percentage of patients having at least a 50% reduction of monthly migraine attacks and migraine days between baseline and the last month of eTNS. Secondary analyses evaluated associations between BOLD signal changes and clinical features of migraine. Before eTNS treatment, there was no difference in BOLD response between MwoA patients and healthy controls (HC) during low-innocuous THS at 41°C, whereas the perigenual part of the right anterior cingulate cortex (ACC) revealed a greater BOLD response to noxious THS at 51°C in MwoA patients when compared to HC. The same area demonstrated a significant reduced BOLD response induced by the noxious THS in MwoA patients after eTNS (p = 0.008). Correlation analyses showed a significant positive correlation between ACC BOLD response to noxious THS before eTNS treatment and the decrease of ACC BOLD response to noxious THS after eTNS. Moreover, a significant negative correlation in the migraine group after eTNS treatment between ACC functional activity changes and both the perceived pain ratings during noxious THS and pre-treatment migraine attack frequency has been found. Our findings suggest that eTNS treatment with the Cefaly® device induces a functional antinociceptive modulation in the ACC that is involved in the mechanisms underlying its preventive anti-migraine efficacy. Nevertheless, further observations to confirm whether the observed fMRI effects of eTNS are both related to clinical improvement and specific to antinociceptive modulation in migraine patients are mandatory.
Highlights
Migraine is the most prevalent neurological disorder worldwide and ranked sixth among the leading causes of years lived with disability [1]
A fluorodeoxyglucose-positron emission tomography (FDG-PET) study showed that external trigeminal neurostimulation (eTNS) with the Cefaly® device was able to increase activity in crucial areas of the limbic system and salience matrix such as orbitofrontal (OF) and anterior cingulate cortex (ACC) in migraine patients responding to the treatment [8]
We found that the BOLD response to noxious trigeminal heat stimulation (THS) (51°C) was increased in the perigenual ACC in migraine without aura (MwoA) patients between attacks compared to healthy controls (HC)
Summary
Migraine is the most prevalent neurological disorder worldwide and ranked sixth among the leading causes of years lived with disability [1]. A fluorodeoxyglucose-positron emission tomography (FDG-PET) study showed that eTNS with the Cefaly® device was able to increase activity in crucial areas of the limbic system and salience matrix such as orbitofrontal (OF) and anterior cingulate cortex (ACC) in migraine patients responding to the treatment [8]. This suggests that eTNS may be able to modulate neuronal circuits involved in the descending pain control of trigeminovascular nociceptors in the spinal trigeminal nucleus [3]. We decided to explore with whole-brain BOLD fMRI the functional reorganization of the pain processing network during trigeminal heat stimulation (THS) after 60 days of eTNS with the Cefaly® device in migraine without aura (MwoA) patients between attacks
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