Relatively little is known on pain-induced neurotransmitter release in the human cerebral cortex. We used proton magnetic resonance spectroscopy (1H-MRS) during tonic painful heat stimulation to test the hypothesis of increases in both glutamate and GABA, two neurotransmitters with a key role in pain processing. Using a 3T MR scanner, we acquired spectra from the rostral anterior cingulate cortex (rACC) in 13 healthy right-handed subjects at rest and during painful heat stimulation. The painful stimulus consisted of a suprathreshold painful tonic heat pulse, which was delivered to the right upper leg via a fMRI-compatible Peltier element. Compared to non-painful stimulation, painful tonic heat was associated with a significant increase in GABA concentrations in the rACC. No changes in glutamate concentrations were detected during noxious stimulation. This study provides the first evidence that GABA is released in the human cerebral cortex during painful stimulation. The results are in line with animal findings on the role of GABA in pain processing and with studies in humans showing analgesic efficacy of GABA-related drugs in clinical pain conditions.

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Purpose of reviewThe underlying mechanisms of migraine are complex and heterogenous. Advances in neuroimaging techniques during the past few decades have contributed to our understanding of migraine pathophysiology. Brain function in migraine patients has been widely explored using functional MRI (fMRI). This review will highlight the major fMRI findings that characterize the different phases of migraine. Recent findingsThe migraine attack starts with hypothalamic hyperexcitability and early reorganization of the common ascending pain and central trigeminovascular pathways. Moreover, the visual cortex becomes hyperexcitable during the aura phase. During the headache phase, further disruptions of the pontine, thalamic, sensorimotor and visual networks occur, although the hypothalamic activity and connectivity normalizes. The visual cortex remains hyperexcitable during the postdromal phase. Asymptomatic migraine patients can also experience functional alternations of pain and visual processing brain areas. At present, the heterogeneity of the asymptomatic phase and fMRI findings make it difficult to find common denominator.Summary fMRI studies have captured functional brain changes associated with migraine phases, leading to an improvement of our understanding of migraine pathophysiology. Further MRI studies are needed to disclose whether the migraine attack is triggered by intrinsic brain dysfunction or external factors. Keywords chronic migraine, functional connectivity, headache, migraine with aura, migraine without aura FUNCTIONAL MRI SEQUENCES USED TO STUDY MIGRAINETwo main fMRI sequences have been applied in migraine studies to investigate brain function: task-based fMRI, and resting-state (i.e. functional