A PET study exploring the laterality of brainstem activation in migraine using glyceryl trinitrate

Abstract

Migraine is a common disabling condition likely to be associated with dysfunction of brain pathways involved in pain and other sensory modalities. A cardinal, indeed signature, feature of the disorder that led to its name is that the pain may be lateralized. H(2)15O-labelled PET was used to study 24 migraineurs and eight healthy controls. The migraineurs were divided into three groups according to the site of their headache: right, left or bilateral. In each group, a migraine was induced using a glyceryl trinitrate (GTN) infusion. The subjects were scanned at predefined points: pre-infusion, during GTN, during migraine and post-migraine. SPM99 software was used to analyse the data. Significant brainstem activation was seen in the dorsal lateral pons (P < 0.05 after small volume correction) during the migraine state versus the pain-free state when comparing migraineurs with controls. When each group was analysed separately, to investigate laterality, it was found that the dorsal pontine activation was ipsilateral in the right-sided and left-sided groups and bilateral in the bilateral headache group with a left-sided preponderance. Consistent with previous work, the activation persisted after pain was controlled by sumatriptan. These results suggest that lateralization of pain in migraine is due to lateralized brain dysfunction.

Trigeminal Nociceptive Transmission in Migraineurs Predicts Migraine Attacks

“…Further evidence for deficient inhibition comes from a study reporting hypofunctional structures in the midbrain in migraineurs (Moulton et al, 2008). Moreover, impaired iron homeostasis in the PAG (Welch et al, 2001;Kruit et al, 2009) and highly specific activation in the rostral pons (localization of the locus coreleus) during an acute migraine attack have been observed (Weiller et al, 1995;Afridi et al, 2005). In line with this latter finding, we also observed-for the first time using fMRI-that migraineurs showed a significant increase in activation of rostral parts of the pons during trigeminonociceptive stimulation.…”

“…Migraineurs are characterized by an alteration of the interictal cortical excitability level, pointing to a deficit of filter mechanisms that is believed to protect individuals against sensory overload (Aurora et al, 2007;Coppola et al, 2007). During the headache attack, the function of brainstem nuclei involved in endogenous pain control and pain transmission is thought to be altered (Afridi et al, 2005;Lambert and Zagami, 2009). Consequently, a dysfunction of peripheral and central parts of the trigeminovascular system is of specific interest (Borsook et al, 2006;DaSilva et al, 2007).…”

“…However, a crucial question is: which structure of the CNS acts as a catalyst? Many brainstem areas, including dorsolateral pons, basilar pons, pontine tegmentum, medial longitudinal fasciculus, periaqueductal gray (PAG), and central midbrain, have been previously discussed (Weiller et al, 1995;Bahra et al, 2001;Cao et al, 2002;Afridi et al, 2005;Denuelle et al, 2007) and it is by no means clear at what time point and for how long these structures show abnormal activity (May, 2009b).…”

Hypothalamic Deep Brain Stimulation in Positron Emission Tomography

“…Neuroimaging with positron emission tomography (PET) shed light on the genesis of two of the most important headache syndromes, documenting activation in the midbrain and pons in migraine (Afridi et al, 2005) and in the hypothalamic gray in cluster headache (CH) (May et al, 1998;Sprenger et al, 2004). These areas are not simply involved as a response to first division nociceptive pain impulses but are inherent to each syndrome, probably in some permissive or dysfunctional role (Goadsby, 2002;May, 2005).…”

Transient Burning Pain in the Ipsilateral Orbit as an Initial Manifestation of Dorsal Pontine Hemorrhage -Case Report-

“…8,11) Positron emission tomography studies have revealed that significant activation is seen in the brainstem, especially in the dorsal lateral pons, in patients with migraine without aura 13) and migraine triggered by 1,2-glyceryl trinitrate. 2,3) Therefore, involvement of the dorsal lateral pons is thought to initiate migraine or migraine-like headache. 1,8,10,11) Interestingly, one case involved a lesion located in almost the same region as in the present case.…”