Experimental Migraine Model Research Articles

Vascular head pain selectively activates ventrolateral periaqueductal gray in the cat

Electrical stimulation of the superior sagittal sinus is an experimental model of migraine which activates neurons within the upper cervical spinal cord. The ventrolateral periaqueductal gray has been proposed as an integrative centre for the autonomic and behavioural responses to deep pain and also receives significant inputs from the upper cervical spinal cord. The noxious-stimulation evoked expression of the immediate-early gene c-fos, was used to determine if sagittal sinus stimulation activates neurons of the ventrolateral periaqueductal gray. The superior sagittal sinus was stimulated in anesthetised cats and Fos-protein was detected in coronal brain sections using standard avidin-biotin immunohistochemistry. A pattern of Fos-positive cells restricted to the caudal ventrolateral periaqueductal gray was revealed suggesting that this region may mediate the pattern of somatic and autonomic responses characteristic of migraine.

Effect of a serotonin agonist (sumatriptan) on the peptidergic innervation of the rat cerebral dura mater and on the expression of c-fos in the caudal trigeminal nucleus in an experimental migraine model

The supratentorial cerebral dura of the albino rat is equipped with a rich sensory innervation including nociceptive axons and their terminals, which display intense calcitonin gene-related peptide (CGRP) immunoreactivity both in the connective tissue and around blood vessels. Stereotactic electrical stimulation of the trigeminal (Gasserian) ganglion, regarded as an experimental migraine model, induces marked increase and disintegration of club-like perivascular CGRP-immunopositive nerve endings in the dura. Intravenous administration of sumatriptan, prior to electrical stimulation, prevents disintegration of perivascular terminals and induces accumulation of CGRP in terminal and preterminal portions of peripheral sensory axons. Consequently, immunopositive terminals and varicosities increase in size; accumulation of axoplasmic organelles results in a "hollow" appearance of many varicosities. Since sumatriptan exerts its anti-migraine effect by virtue of its agonist action on 5-HT1D receptors, we suggest that sumatriptan prevents the release of CGRP from dural perivascular terminals by an action at 5-HT1D receptors. In the caudal trigeminal nucleus electrical stimulation of the trigeminal ganglion induces, in interneurons, increased expression of the oncoprotein c-fos which is not prevented by intravenous application of sumatriptan. Disparate findings regarding this effect are partly due to the fact that sumatriptan very poorly passes the blood-brain barrier and partly to different experimental paradigms used by different authors.

Effect of a serotonin agonist (sumatriptan) on the peptidergic innervation of the rat cerebral dura mater and on the expression of c‐fos in the caudal trigeminal nucleus in an experimental migraine model

Effect of a serotonin agonist (sumatriptan) on the peptidergic innervation of the rat cerebral dura mater and on the expression of c‐fos in the caudal trigeminal nucleus in an experimental migraine model

Effects of tertatolol, a β-adrenoceptor antagonist with agonist affinity at 5-HT 1A receptors, in an animal model of migraine: comparison with propranolol and pindolol

Constriction of carotid arteriovenous anastomoses is a common property of several antimigraine drugs. The present study concerns the effects of tertatolol (0.1, 0.3, 1 and 3 mg/kg i.v.), a novel β-adrenoceptor antagonist with an agonist action on 5-HT 1A receptors, on systemic haemodynamics and carotid blood flow distribution in the anaesthetized pig. Two other β-adrenoceptor antagonists, one (propranolol) with and one (pindolol) without antimigraine actions, were compared (doses: 0.03, 0.1, 0.3 and 1 mg/kg i.v.) with tertatolol in this animal experimental model of migraine. While the β-adrenoceptor antagonist with partial agonist action, pindolol, increased heart rate and cardiac output, propranolol and tertatolol decreased these variables moderately. Mean arterial blood pressure also decreased with the two highest doses of propranolol and with the highest dose of tertatolol. The calculated total peripheral conductance decreased with the first three doses of tertatolol. Carotid haemodynamic variables were not affected by pindolol, except for some increase in the nutrient fraction after the highest dose. Propranolol and especially tertatolol decreased both total carotid blood flow and arteriovenous anastomotic blood flow without affecting the nutrient fraction. In the case of tertatolol, blood flow decreases were accompanied by similar decreases in vascular conductance, indicating active arteriovenous anastomotic constriction. It is therefore suggested that tertatolol may prove effective in the treatment of migraine.

Migraine-like accompaniments of vitreous detachment

Vitreous detachment is occasionally associated with complex visual disturbances and/or cephalgia, not just flashes and floaters. The author analyzes his experience with unusual symptoms described by patients suffering acute vitreous detachment and concludes that many of them resemble symptoms experienced by migraineurs. He reviews experimental models of migraine in the context of retinal neuronal spreading depression and speculates that electrical disturbances of the retina may be related to a variety of visual symptoms of an acute or subacute nature.

Regional cerebral blood flow during cortical spreading depression in rat brain: increased reactive hyperperfusion in low-flow states.

The purpose of the present study was to characterize the initial vascular events accompanying cortical spreading depression (CSD) of the rat brain. Regional cerebral blood flow (rCBF) was measured during the first 1-2 min of CSD using 14C-iodoantipyrine autoradiography. The material included a reference group, and 4 groups where rCBF was altered by indomethacin treatment, hypo- or hypercapnia, or one previous episode of CSD. rCBF did not change prior to, or during the onset of CSD. Thirty seconds later, rCBF increased depending on the pre-existing level of blood flow, i.e. the rise of rCBF was pronounced at depressed flow levels, but small or absent at normal or high flow levels. The prevalent view that CSD is intimately associated with vasodilatation was accordingly not supported. The activated rCBF in normocapnic rats ranged between 93 and 175 ml/100g/min, supranormal values were the exception rather than the rule. The rCBF rise, when present, probably succeeds a period of brain hypoxia, and should be classified as a reactive hyperfusion. The results together with earlier clinical and experimental findings, support that CSD may serve as experimental migraine model.

Long-lasting reduction of cortical blood flow of the brain after spreading depression with preserved autoregulation and impaired CO2 response.

The purpose of the present study was to examine the cerebral perfusion after spreading depression with special emphasis on its relation to the perfusion changes in migraine. The cerebrovascular reactivity to changes of arterial PCO2 tension in the range of 24-70 mm Hg and to changes of MABP in the range of 55-150 mm Hg was studied in the rat brain after one episode of cortical spreading depression. Regional CBF (rCBF) was measured in the frontal, parietal, and occipital cortex, the basal ganglia, and the cerebellum of both hemispheres after the intravenous bolus injection of [14C]iodoantipyrine. rCBF decreased in the cortical regions to 69-73% of control values for 1 h after spreading depression in every single rat, but remained unchanged in the basal ganglia and cerebellum. CBF changed with alterations of arterial carbon dioxide tension in all brain regions. In control regions, CBF changed by 2.8-3.9% per mm Hg PaCO2 change, whereas in the spreading depression cortex, CBF changed by only 1.3-1.5%. The difference between control and spreading depression cortex was significant at p less than 0.001, indicating a reduced CO2 sensitivity of the cortical regions invaded by spreading depression. rCBF remained unchanged in all brain regions in the MABP range of 80-150 mm Hg, reflecting the intact autoregulatory function of the two sides, and at a MABP of less than 80 mm Hg, rCBF decreased in parallel in symmetrical regions. It is concluded that the hypoperfusion after spreading depression is due to a vasoconstrictor stimulus overriding the vasodilatory effect of acid pH.(ABSTRACT TRUNCATED AT 250 WORDS)