Alterations in pain processing circuitries in episodic migraine

Abstract

Background The 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. Methods Functional 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. Results Despite 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. Conclusions These 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.

Applying a biopsychosocial model to migraine: rationale and clinical implications

“…Thus, migraine is regarded as a “connectopathy” rather than a disease arising from dysfunctioning of specific areas of the brain. Interestingly, the same technique also showed a heightened connection between sensory areas and areas regulating affective processes including the limbic system [ 25 – 28 ], which is implied in pain processing and in the regulation of emotional life. This may explain migraineurs’ susceptibility to external triggers causing sensory overload; those triggers may modify brain circuits functioning [ 29 – 31 ].…”

Efficacy of repetitive transcranial magnetic stimulation on chronic migraine: A meta-analysis

“…Previous study suggested that the etiology of migraine is dysfunction of the pain regulation pathway ( 36 ), the PET study by Lorenz et al ( 37 ) found that substantial prefrontal cortex activation during heat stimuli on capsaicin-treated skin. Meanwhile, the current fMRI study by Mungoven et al ( 38 ) found that reduced whole scan the dorsolateral prefrontal cortex (DLPFC) connectivity with cortical/subcortical and brainstem regions involved in pain modulation was demonstrated in migraineurs. Furthermore, the functional connection between brain regions that play an important role in regulating pain is significantly weakened, suggesting that migraine could be relieved if the dysfunction of the pain regulation pathway is improved ( 39 ).…”

Right-to-Left Shunt-associated Brain Functional Changes in Migraine: Evidences from a Resting-state FMRI Study

“…Numerous rs-fMRI studies have been conducted to elucidate the physiological underpinnings of migraine (Messina R et al, 2022). In particula, aberrant descending pain modulatory pathway prior to the migraine attack, abnormal thalamo-cortical and frontoparietal pathways involved in pain transmission and modulation have been observed in migraine individuals Nie W et al, 2021;Lim M et al, 2021;Mungoven TJ et al, 2022) In this study, we posit a potential correlation between RLS and functional alterations in integration and segregation in individuals with migraines. To examine this hypothesis, the study meticulously explores RLS-associated brain functional aberrations in migraine individuals with and without RLS The overarching goal is to unravel the underlying connection between RLS and migraines, contributing to a comprehensive understanding of this intricate interplay.…”