Neuronal correlates of impaired habituation in response to repeated trigemino-nociceptive but not to olfactory input in migraineurs: an fMRI study.

INTRODUCTION: Using functional magnetic resonance imaging (fMRI), we aimed to explore the habituation behaviour to trigemino-nociceptive as well as olfactory stimuli in migraine patients. We exclusively focussed on intrasessional behavioural rating patterns and the related blood oxygen level dependent (BOLD) signal changes. FINDINGS: We observed that groups significantly differ in the time course of pain intensity ratings during the stimulation session: whereas interictal migraineurs sensitized (increasing pain ratings), control subjects habituated (decreasing pain ratings). Pain ratings of ictal patients remained unchanged. This behaviour is accompanied by a similar time course of neuronal activity in the bilateral anterior insula, in the middle cingulate cortex and in the thalamus. In these areas, the brain activity increased in migraineurs but decreased in the control group during the session. In contrast to these findings, the rating patterns for the olfactory stimuli (rose odour) did not differ between patients and controls and a gradual decrease of perceived stimulus intensity was found in all three groups. This stimulus specific response may occur because the olfactory system is the only sensory system not passing the thalamus. CONCLUSION: Our data suggest that impaired habituation in functional brain systems in migraine is fundamental only to specific modalities including the trigemino-nociceptive, but, at least, excluding the olfactory system. Our findings further suggest that there is no single neuronal modulator responsible for the altered rating pattern in migraineurs.

A new trigemino-nociceptive stimulation model for event-related fMRI.

Functional imaging of human trigemino-nociceptive processing provides meaningful insights into altered pain processing in head and face pain diseases. Although functional magnetic resonance imaging (fMRI) offers high temporal and spatial resolution, most studies available were done with radioligand-positron emission tomography, as fMRI requires non-magnetic stimulus equipment and fast on-off conditions. We developed a new approach for painful stimulation of the trigeminal nerve that can be implemented within an event-related design using fMRI and aimed to detect increased blood-oxygen-level-dependent (BOLD) signals as surrogate markers of trigeminal pain processing. Using an olfactometer, 20 healthy volunteers received intranasally standardized trigeminal nociceptive stimuli (ammonia gas) as well as olfactory (rose odour) and odorless control stimuli (air puffs). Imaging revealed robust BOLD responses to the trigeminal nociceptive stimulation in cortical and subcortical brain areas known to be involved in pain processing. Focusing on the trigeminal pain pathway, significant activations were observed bilaterally in brainstem areas at the trigeminal nerve entry zone, which are agreeable with the principal trigeminal nuclei. Furthermore, increased signal changes could be detected ipsilaterally at anatomical localization of the trigeminal ganglion and bilaterally in the rostral medulla, which probably represents the spinal trigeminal nuclei. However, brainstem areas involved in the endogenous pain control system that are close to this anatomical localization, such as raphe nuclei, have to be discussed. Our findings suggest that mapping trigeminal pain processing using fMRI with this non-invasive experimental design is feasible and capable of evoking specific activations in the trigeminal nociceptive system. This method will provide an ideal opportunity to study the trigeminal pain system in both health and pathological conditions such as idiopathic headache disorders.

[Cortical dysbalance in the brain in migraineurs--hyperexcitability as the result of sensitisation?]. / Kortikale Dysbalance des Migränikerhirns--Hyperexzitabilität als Folge einer Sensitisierung?

A cortical dysbalance has a pivotal role in the pathophysiology of migraine. Numerous electrophysiological and transcranial magnetic stimulation (TMS) studies have investigated the interictal excitability level in migraineurs and have shown a consistent lack of habituation during repetitive stimulation. There is some controversy in the current literature over whether this deficit is based on a lowered or an elevated preactivation level. However, the current discussion may be misguided. It seems that multiple external and intrinsic factors influence the level of cortical excitability and the frequency and intensity of attacks: Habituation is specific neither to migraine nor even to pain; the same phenomenon is found in tinnitus patients, for example. Cortical hyperexcitability is presumably the result of chronicity and the concomitant central sensitisation process.