Functional interictal changes of pain processing in migraine with ictal cutaneous allodynia

Objective: A prospective clinical imaging study has been conducted to investigate pain processing functional pathways during trigeminal heat stimulation (THS) in patients with migraine without aura experiencing ictal cutaneous allodynia (CA) (MwoA CA+). Methods: Using whole-brain BOLD-fMRI, functional response to THS at three different intensities (41 degrees, 51 degrees and 53 degrees C) was investigated interictally in 20 adult MwoA CA+ patients compared with 20 MwoA patients without ictal CA (MwoA CA-) and 20 healthy controls (HCs). Secondary analyses evaluated associations between BOLD signal change and clinical features of migraine. Results: During moderate-noxious THS (51 degrees C), we observed a significantly greater activation in (a) the anterior cingulate cortex in MwoA CA+ patients compared to HCs and (b) the middle frontal gyrus in MwoA CA+ patients compared to both MwoA CA- patients and HCs. Furthermore, during high-noxious THS (53 degrees C) a significantly decreased activation in the secondary somatosensory cortices was observed in (a) MwoA CA- patients compared to both MwoA CA+ patients and HCs and (b) MwoA CA+ patients compared to HCs. CA severity was positively correlated with the secondary somatosensory cortices activation. Conclusions: Our findings suggest that CA may be subtended by both a dysfunctional analgesic compensatory mechanism and an abnormal internal representation of pain in migraine patients.