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Updated: Oct 6, 2025

3D-Neuronavigation In Vivo Through a Patient's Brain During a Spontaneous Migraine Headache
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Alterations in pain processing circuitries in episodic migraine.

Tiffani J Mungoven1, Kasia K Marciszewski1, Vaughan G Macefield2

  • 1School of Medical Sciences (Neuroscience), Brain and Mind Centre, University of Sydney, Camperdown, NSW, 2050, Australia.

The Journal of Headache and Pain
|January 16, 2022
PubMed
Summary

Migraineurs show altered brain activity and connectivity in higher cortical regions before an attack, suggesting aberrant descending pain modulation. These changes in the dorsolateral prefrontal cortex (dlPFC) pathway are specific to the pre-migraine phase.

Keywords:
Brainstem pain modulationCortical pain modulationDorsolateral prefrontal cortexFunctional connectivityHypothalamusMigraineOrofacial painPPISpinal trigeminal nucleus

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Area of Science:

  • Neuroscience
  • Pain Research
  • Neuroimaging

Background:

  • The exact mechanisms of migraine are not fully understood.
  • Previous studies indicated brainstem changes in migraineurs during orofacial pain.
  • It remains unclear if higher brain regions influence these brainstem alterations.

Purpose of the Study:

  • To investigate altered activation and connectivity in higher brain centers of migraineurs during noxious orofacial stimuli.
  • To determine if cortical regions modulate brainstem activity in migraine.

Main Methods:

  • Functional magnetic resonance imaging (fMRI) was used in 29 healthy controls and 25 migraineurs.
  • Scans were conducted during interictal periods and immediately before migraine attacks (within 24 hours).
  • Noxious orofacial heat stimulation was applied using a thermode to assess cortical activation and connectivity.

Main Results:

  • Migraineurs before an attack showed increased activation in the nucleus accumbens, ventrolateral prefrontal cortex, and dorsolateral prefrontal cortex (dlPFC).
  • Reduced dlPFC connectivity with pain-modulating regions (putamen, primary motor cortex) was observed in migraineurs.
  • Migraineurs exhibited reduced pain-related connectivity between the dlPFC, hypothalamus, and brainstem pain modulatory areas (rostral ventromedial medulla, dorsolateral pons) prior to migraine.

Conclusions:

  • Higher cortical regions may abnormally modulate brainstem pain pathways in migraineurs.
  • These aberrant descending pain modulation alterations are specific to the pre-migraine phase.
  • This suggests a critical role for descending pain modulation in migraine pathophysiology.