Our ability to have an experience of another's pain is characteristic of empathy. Using functional imaging, we assessed brain activity while volunteers experienced a painful stimulus and compared it to that elicited when they observed a signal indicating that their loved one--present in the same room--was receiving a similar pain stimulus. Bilateral anterior insula (AI), rostral anterior cingulate cortex (ACC), brainstem, and cerebellum were activated when subjects received pain and also by a signal that a loved one experienced pain. AI and ACC activation correlated with individual empathy scores. Activity in the posterior insula/secondary somatosensory cortex, the sensorimotor cortex (SI/MI), and the caudal ACC was specific to receiving pain. Thus, a neural response in AI and rostral ACC, activated in common for "self" and "other" conditions, suggests that the neural substrate for empathic experience does not involve the entire "pain matrix." We conclude that only that part of the pain network associated with its affective qualities, but not its sensory qualities, mediates empathy.

Evidence from animal experiments shows that the brain stem is involved in the pathophysiology of migraine. To investigate human migraine, we used positron emission tomography to examine the changes in regional cerebral blood flow as an index of neuronal activity in the human brain during spontaneous migraine attacks. During the attacks, increased blood flow was found in the cerebral hemispheres in cingulate, auditory and visual association cortices and in the brain stem. However, only the brain stem activation persisted after the injection of sumatriptan had induced complete relief from headache and phono- and photophobia. These findings support the idea that the pathogenesis of migraine is related to an imbalance in activity between brain stem nuclei regulating antinociception and vascular control.

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.

Background: Functional brain imaging in acute migraine has proved challenging because of the logistic problems associated with an episodic condition. Since the seminal observation of brainstem activation in migraine, there has been only a single case substantiating this finding.Objective: To test the hypothesis that brainstem activation could be detected in migraine and to refine the anatomic localization with higher-resolution positron emission tomography than previously used.Design: Using positron emission tomography with radioactive water (H 2 15 O), we studied acute migraine attacks occurring spontaneously. Five patients underwent imaging in ictal and interictal states, and the differences were analyzed by means of statistical parametric mapping.Setting: Tertiary referral center.Patients: Six volunteers with episodic migraine were recruited from advertisements in migraine newsletters. One patient was excluded because of use of preventive medication.Main Outcome Measure: Brainstem activation during migraine state vs interictal state.Results: Two patients had a typical migrainous aura before the onset of the headache. All of the attacks studied fulfilled standard diagnostic criteria for migraine. Comparing the migraine scans with interictal scans, there was significant activation in the dorsal pons, lateralized to the left (small volume correction, P=.003). Activation was also seen in the right anterior cingulate, posterior cingulate, cerebellum, thalamus, insula, prefrontal cortex, and temporal lobes. There was an area of deactivation in the migraine phase also located in the pons, lateralized to the right. Conclusions:Our findings provide clear evidence of dorsal pontine activation in migraine and reinforce the view that migraine is a subcortical disorder modulating afferent neural traffic.

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Studying attacks of migraine is considerably hampered by its fundamentally episodic nature. Developing approaches to triggering migraine reliably is important for advancing understanding of the disorder by facilitating its study. Based on the work of the Copenhagen Group we administered an intravenous infusion of 0.5 microg/kg/min glyceryl trinitrate (GTN) to 44 migraineurs, 23 migraine without aura, 21 migraine with aura, and to 12 healthy controls. We sought to characterise the GTN-induced migraine in terms of the clinical features of the attacks and reproducibility of triggering, and included a non-migraine control group for the purpose of comparing any effects to exclude an ordering effect. Of the 44 patients administered GTN, 33 had a migraine attack fulfilling International Headache Society criteria. Thirty-two attacks were of migraine without aura and one of migraine with aura. Twelve patients described typical premonitory symptoms, which have not been previously documented with GTN-induced migraine. A repeat attack was triggered in all subjects but one. In one case a visual aura was also triggered both times. Our study shows that GTN-induced triggering is common in our patients, and remarkably reproducible. The data will facilitate the use of the GTN model in studies requiring extensive planning, such as brain imaging, or where preventive questions are at issue. We also report the first patient with a reproducible GTN-triggered migraine with aura.

1 The detailed pathophysiology of migraine is beginning to be understood and is likely to involve activation of trigeminovascular a erents.2 Clinically e ective anti-migraine compounds are believed to have actions that include peripheral inhibition of calcitonin gene-related peptide (CGRP) release from trigeminal neurones, or preventing dural vessel dilation, or both. CGRP antagonists can block both neurogenic and CGRP-induced dural vessel dilation. 3 Nitric oxide (NO) can induce headache in migraine patients and often triggers a delayed migraine. The initial headache is thought to be caused via a direct action of the NO ± cGMP pathway that causes vasodilation by vascular smooth muscle relaxation, while the delayed headache is likely to be a result of triggering trigeminovascular activation. Nitric oxide synthase (NOS) inhibitors are e ective in the treatment of acute migraine. 4 The present studies used intravital microscopy to examine the e ects of speci®c NOS inhibitors on neurogenic dural vasodilation (NDV) and CGRP-induced dilation. 5 The non-speci®c and neuronal NOS (nNOS) inhibitors were able to partially inhibit NDV, while the non-speci®c and endothelial NOS (eNOS) inhibitors were able to partially inhibit the CGRP induced dilation. 6 There was no e ect of the inducible NOS (iNOS) inhibitor. 7 The data suggest that the delayed headache response triggered by NO donors in humans may be due, in part, to increased nNOS activity in the trigeminal system that causes CGRP release and dural vessel dilation. 8 Further, eNOS activity in the endothelium causes NO production and smooth muscle relaxation by direct activation of the NO ± cGMP pathway, and may be involved in the initial headache response.

Using a positron emission tomography (PET) study it was shown recently that in migraine without aura certain areas in the brain stem were activated during the headache state, but not in the headache free interval. It was suggested that this brain stem activation is inherent to the migraine attack itself and represents the so called 'migraine generator'. To test this hypothesis we performed an experimental pain study in seven healthy volunteers, using the same positioning in the PET scanner as in the migraine patients. A small amount of capsaicin was administered subcutaneously in the right forehead to evoke a burning painful sensation in the first division of the trigeminal nerve. Increases of regional cerebral blood flow (rCBF) were found bilaterally in the insula, in the anterior cingulate cortex, the cavernous sinus and the cerebellum. Using the same stereotactic space limits as in the above mentioned migraine study no brain stem activation was found in the acute pain state compared to the pain free state. The increase of activation in the region of the cavernous sinus however, suggests that this structure is more likely to be involved in trigeminal transmitted pain as such, rather than in a specific type of headache as was suggested for cluster headache.