Increased cerebral responses to salient transitions between alternating stimuli in chronic migraine with medication overuse headache and during migraine attacks

Introduction
In a previous study exploring central pain modulation with heterotopic stimuli in healthy volunteers, we found that transitions between sustained noxious and innocuous thermal stimulations on the foot activated the “salience matrix”. Knowing that central sensory processing is abnormal in migraine, we searched in the present study for possible abnormalities of these salient transitional responses in different forms of migraine and at different time points of the migraine cycle.

Methods
Participants of both sexes, mostly females, took part in a conditioned pain modulation experiment: Migraineurs between (n = 14) and during attacks (n = 5), chronic migraine patients with medication overuse headache (n = 7) and healthy volunteers (n = 24). To evoke the salience response, continuous noxious cold or innocuous warm stimulations were alternatively applied on the right foot. Cerebral blood oxygenation level dependent responses were recorded with fMRI.

Results
Switching between the two stimulations caused a significant transition response in the “salience matrix” in all subject groups (effect of the condition). Moreover, some group effects appeared on subsequent post-hoc analyses. Augmented transitional blood oxygenation level dependent responses in the motor cortex and superior temporal sulcus were found in two patient groups compared to healthy controls: chronic migraine with medication overuse headache patients and migraineurs recorded during an attack. In chronic migraine with medication overuse headache patients, salience-related responses were moreover greater in the premotor cortex, supplementary motor area, lingual gyrus and dorso-medial prefrontal cortex and other “salience matrix” areas, such as the anterior cingulate and primary somatosensory cortices.

Conclusion
This study shows salience-related hyperactivation of affective and motor control areas in chronic migraine with medication overuse headache patients and, to a lesser extent, in episodic migraine patients during an attack. The greater extension of exaggerated blood oxygenation level dependent responses to unspecific salient stimuli in chronic migraine with medication overuse headache than during a migraine attack could be relevant for headache chronification.