Abstract
BackgroundThe precise underlying mechanisms of migraine remain unknown. Although we have previously shown acute orofacial pain evoked changes within the brainstem of individuals with migraine, we do not know if these brainstem alterations are driven by changes in higher cortical regions. The aim of this investigation is to extend our previous investigation to determine if higher brain centers display altered activation patterns and connectivity in migraineurs during acute orofacial noxious stimuli.MethodsFunctional magnetic resonance imaging was performed in 29 healthy controls and 25 migraineurs during the interictal and immediately (within 24-h) prior to migraine phases. We assessed activation of higher cortical areas during noxious orofacial heat stimulation using a thermode device and assessed whole scan and pain-related changes in connectivity.ResultsDespite similar overall pain intensity ratings between all three groups, migraineurs in the group immediately prior to migraine displayed greater activation of the ipsilateral nucleus accumbens, the contralateral ventrolateral prefrontal cortex and two clusters in the dorsolateral prefrontal cortex (dlPFC). Reduced whole scan dlPFC [Z + 44] connectivity with cortical/subcortical and brainstem regions involved in pain modulation such as the putamen and primary motor cortex was demonstrated in migraineurs. Pain-related changes in connectivity of the dlPFC and the hypothalamus immediately prior to migraine was also found to be reduced with brainstem pain modulatory areas such as the rostral ventromedial medulla and dorsolateral pons.ConclusionsThese data reveal that the modulation of brainstem pain modulatory areas by higher cortical regions may be aberrant during pain and these alterations in this descending pain modulatory pathway manifests exclusively prior to the development of a migraine attack.
Highlights
The precise underlying mechanisms of migraine remain unknown
Analgesic responses can be evoked by injections of morphine into either the periaqueductal gray matter (PAG) or nucleus accumbens (NAc) [39, 40] and we have previously shown in humans that the NAc is involved in conditional pain modulation (CPM) analgesia [41]
We found that increased activation of the dorsolateral prefrontal cortex (dlPFC) in migraineurs immediately prior to a migraine was associated with reduced whole scan connectivity with other pain processing regions such as the VP thalamus, orbitofrontal cortex and the hypothalamus
Summary
The precise underlying mechanisms of migraine remain unknown. we have previously shown acute orofacial pain evoked changes within the brainstem of individuals with migraine, we do not know if these brainstem alterations are driven by changes in higher cortical regions. Mungoven et al The Journal of Headache and Pain (2022) 23:9 increasing on-going neural traffic within the SpV or by allowing an external trigger to increase SpV activity; both of which would increase activation of cortical areas and elicit head pain [4] Consistent with this brainstem oscillation hypothesis, we recently reported that in episodic migraineurs, acute noxious orofacial stimulation evoked greater activation of the SpV compared with controls during the 24-h period immediately prior to a migraine attack and not during the interictal period [5]. This increased activation occurred despite the overall perceived pain intensities being no different to that of the control group [5]. The most well-described brainstem pain modulatory pathway involves the midbrain periaqueductal gray matter (PAG) - RVM - SpV circuit [6,7,8,9,10,11] and our results suggest that migraine is associated with fluctuations in descending pain modulatory pathways over the migraine cycle [5]
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