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H Kaube

Publications and source records attributed to H Kaube.

14 recordsLinked to original sources
PubMed1996

Central activation of the trigeminovascular pathway in the cat is inhibited by dihydroergotamine. A c-Fos and electrophysiological study.

Recent studies have delineated a clear role for the trigeminal innervation of pain-sensitive intracranial structures in the pathophysiology of migraine. The development of new compounds for the treatment of the acute attack of migraine has led to a greater understanding of serotonin (5-hydroxytryptamine; 5HT) receptor diversity. The ergot alkaloids have been used in the treatment of acute attacks of migraine for many years and parenteral administration of dihydroergotamine (DHE) can be a useful treatment strategy. In this study, the question of a possible central site of action of DHE is considered using both anatomical and physiological approaches. The c-Fos method has been used to map functional activation of central neurons in response to stimulation of the superior sagittal sinus (SSS) in the cat. This structure has been used as it refers pain to the ophthalmic division of the trigeminal nerve in humans, and in cats induces changes in neuropeptides and cranial blood flow similar to those seen in migraine. In addition, the temporal aspects of the effect of DHE have been studied by making extracellular recordings from cells in the most caudal aspect of the trigeminal nuclear complex. Stimulation of the SSS results in Fos expression in the superfical laminae of the trigeminal nucleus caudalis and in the dorsal horn of C1 and C2. This activation is blocked by a clinically relevant dose of DHE. Similarly, cells can be recorded in this region that respond to SSS stimulation. This linked cellular activity can be inhibited by the same intravenous dose of DHE. Together, these studies show that DHE can inhibit activity in central trigeminal neurons. Since the sinus and its nerve supply are directly stimulated, the peripheral nerve/vessel innervation is bypassed and this inhibition cannot have happened at any other site. These data imply that drugs acting at the central trigeminal neurons may have a role in the treatment of acute attacks of migraine.

Animals↗
PubMed1995

Brain stem activation in spontaneous human migraine attacks.

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.

Adult↗
PubMed1994

Sumatriptan.

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Aged↗
PubMed1994

Lignocaine and headache: an electrophysiological study in the cat with supporting clinical observations in man.

Chronic daily headache (CDH) is a particularly difficult type of headache to manage, with an uncertain pathophysiology. Intravenous administration of lignocaine has been suggested as a possibly useful option in the control of this syndrome. We have surveyed prospectively patients with CDH (selected for this study as those with 6 or more months of continuous pain with at least weekly exacerbations that, taken in isolation, would fulfil International Headache Society diagnostic criteria for migraine without aura). Intravenous lignocaine (2 mg/min) by infusion over a 2-day period rendered 26% of patients pain free, with a further 42% having at least a 50% improvement in the pain. Continued benefit was associated with commencement of prophylaxis with a tricyclic antidepressant or monoamine oxidase inhibitor after completion of the lignocaine infusion. In an animal model of craniovascular nociception, using electrical stimulation of the superior sagittal sinus and recording of single unit activity and sensory evoked potentials in the spinal trigeminal nucleus in the upper cervical spinal cord of the anaesthetised cat, the effect of lignocaine was examined. Lignocaine reduced both the probability of cell firing and the size of the trigeminal evoked potential in the animals studied. The reduction was both substantial (more than 25% in each case) and dose-dependent. Taken together the data suggest that CDH is likely to be a disorder of central craniovascular nociceptive control and that lignocaine acts to interrupt a part of the pathway involved but is unlikely to act at the central generator of the disorder.

Animals↗
PubMed1994

Anti-migraine compounds fail to modulate the propagation of cortical spreading depression in the cat.

Leao's cortical spreading depression (SD) is often cited as the pathophysiological substrate for the neurological symptoms of migraine with aura. If this is the case it might be expected that drugs useful as anti-migraine agents, particularly those useful in prophylaxis, may alter or prevent SD. Indeep it has been suggested that the anti-migraine compound dihydroergotamine (DHE) blocks or reduces the speed of propagation of SD in the rabbit. In this study we attempted to further investigate the effects of DHE and other anti-migraine drugs on SD by measuring cortical blood flow with laser Doppler flowmetry (CBFLDF) and cortical single unit activity in the alpha-chloralose-anaesthetised cat. The following substances were tested: DHE, acetylsalicylic acid, lignocaine, metoprolol, clonazepam and valproate. The NMDA-receptor blocker MK-801 and halothane (1.5%) were used as reference substances that reliably block SD. The outcome measures were speed of propagation of the wave of SD across the cortex and the CBFLDF increase during the hyperaemic phase of SD. Data were taken from three control episodes (60 min apart) and after drug administration. The rate of propagation was significantly reduced from the first control period (3.0 +/- 0.3 mm/min) to the subsequent 2 control observations (2.3 +/- 0.1 mm/min) even without any drug treatment. Following the control observations the test drug was administered and a further SD elicited. This fourth SD was reliably blocked by MK-801 and halothane. None of the other test drugs inhibited SD, reduced the rate of propagation or changed the amplitude of the CBFLDF increase.(ABSTRACT TRUNCATED AT 250 WORDS)

Analgesics↗
PubMed1993

Expression of c-Fos-like immunoreactivity in the caudal medulla and upper cervical spinal cord following stimulation of the superior sagittal sinus in the cat.

Migraine is an episodic vascular headache with a well-recognized clinical picture but a poorly understood pathogenesis. Stimulation of a pain-sensitive trigeminally innervated intracranial structure, the superior sagittal sinus (SSS), was undertaken to map the higher-order neurons potentially involved in the processing of vascular head pain. The animals were prepared for stimulation by exposure of the sinus and then maintained under alpha-chloralose anaesthesia for 24 h before SSS stimulation, perfusion and immunohistochemical processing for the detection of Fos protein. Examination of the medulla and upper cervical cord revealed marked increases in Fos-like immunoreactivity in laminae I and IIo of the trigeminal nucleus caudalis and the dorsal horn of the upper cervical spinal cord. In addition, Fos-like immunoreactivity was observed in lamina X of the upper cervical spinal cord, in the commissural and medial nuclei of the solitary tract and in the nucleus retroambigualis. The use of immunohistochemical detection of Fos has allowed visualization of several populations of neurons likely to be involved in the central neural processing of vascular headache syndromes, particularly migraine.

Animals↗
PubMed1993

Inhibition by sumatriptan of central trigeminal neurones only after blood-brain barrier disruption.

1. The 5-hydroxytryptamine (5-HT1)-like agonist, sumatriptan, is highly efficient in the relief of migraine headache and its accompanying symptoms. 2. Experimental evidence has indicated that its site of action may be on the cranial vessels or on the trigeminal innervation of the cranium, or both, since sumatriptan does not pass the blood-brain barrier easily under normal circumstances. It is, however, not clear whether the blood-brain barrier is normal or abnormal during a migraine attack. 3. In this study, single unit activity and trigeminal somatosensory evoked potentials in central trigeminal neurones were monitored during electrical stimulation of the superior sagittal sinus. 4. Intravenous administration of sumatriptan (100 micrograms kg-1) did not alter trigeminal evoked activity unless the permeability of the blood-brain barrier had been increased by infusion of an hyperosmolar mannitol solution. After blood-brain barrier disruption, sumatriptan decreased the peak-to-peak amplitude of evoked potentials by 40 +/- 6% and the probability of firing of single units by 30 +/- 9%. Mannitol infusions alone in control animals caused no changes in evoked potentials or single unit activity. 5. The data suggest that in normal circumstances sumatriptan does not have sufficient access to trigeminal neurons to alter their function.

Animals↗
PubMed1992

Nitric oxide synthesis couples cerebral blood flow and metabolism.

The most fundamental aspect of the cerebral circulation is the well-described coupling of cerebral metabolic activity and cerebral blood flow. A number of substances have been proposed to link flow and metabolism, including K+, pH and adenosine. In the alpha-chloralose anaesthetised cat we studied simultaneously cerebral neuronal activity and local blood flow to attempt to dissociate the two and thus determine the coupling substance. Neuronal activity was determined by monitoring unit firing in the parietal cortex with tungsten in glass microelectrodes while local cerebral blood flow in the same area was monitored continuously using laser Doppler flowmetry. To initiate an increase in metabolic activity and, pari passu, blood flow spreading depression was elicited by needle stick injury. Spreading depression when initiated causes a wave of depolarization, measured as an increased firing rate and associated marked (400 +/- 95%) increase in local cerebral blood flow. Intravenous administration of NG-nitro-L-arginine methyl ester (1-NAME), a potent nitric oxide synthase inhibitor, produced a complete blockade of the hyperemia associated with spreading depression but no change in either resting cell firing or spreading depression-evoked increases in firing rate. These data demonstrate at least for spreading depression-elicited increases in metabolic activity, that nitric oxide (NO) is a key coupling compound that links changes in cerebral blood flow and metabolism. These data imply that NO may have a more general role in flow/metabolism coupling and further studies in other situations are required to determine the extent to which NO is responsible for this fundamental cerebrovascular phenomenon.

Animals↗
PubMed1992

Activation of the trigeminovascular system by mechanical distension of the superior sagittal sinus in the cat.

Distension of dural sinuses in man produces migraine-like pain. In eight alpha-chloralose anaesthetized cats mechanical distension of the superior sagittal sinus with a small intraluminal device was used to activate single units in the dorsolateral C2 spinal cord. Units in this region have been shown to respond to electrical stimulation of the superior sagittal sinus in the cat model. Linked responses to mechanical dilatation could only be obtained with very rapid stretching stimuli or high amplitudes of distension of the vessel. Lower thresholds for transduction of distension in the vessel wall may depend on transferral to the dura or biochemical or neural pre-sensitization of the superior sagittal sinus. These data are consistent with the view that migraine is not primarily a vascular disorder but requires at least humoral or neural facilitation.

Animals↗
PubMed1991

Cerebrovascular risk factors in migraine with prolonged aura and without aura.

The role of cerebrovascular risk factors such as mitral valve prolapse, platelet aggregation, platelet activation and cardiac arrythmias in migraine was investigated in a total of 44 migraineurs (32 migraineurs without aura and 12 with prolonged aura) and 32 controls. Comparing the total of migraineurs and the two subgroups with controls, mitral valve prolapse, a raised thromboxane B2 level, at least one platelet aggregation dysfunction or an abnormality in 24-h ECG was statistically seen no more often than in the control group. Neither did combinations of the variables occur more frequently. Altogether, this study showed no increased coincidence of migraine with prolonged aura and migraine without aura with the above parameters. The absence of cardiac and haematological abnormalities in migraine with prolonged aura focuses attention on the control of the cortical microcirculation.

Adolescent↗
PubMed1991

MMPI personality profiles in patients with primary headache syndromes.

The role of psychological factors in the course of primary headache syndromes is still controversial. Using the Minnesota Multiphasic Personality Inventory (MMPI) we investigated the personality profiles of 434 headache patients (160 migraineurs, 95 with tension type headache, 30 with cluster headache and 149 with combination headache) in accordance with the IHS criteria. In the first three MMPI scales (hypochondria, depression, hysteria) there was a slight increase in T mean values to over 60, but still in the range of two standard deviations of the normal population. There were no statistically significant differences between the four headache groups and between patients with and without analgesic abuse. It was impossible to distinguish headache groups on the basis of their personality profiles by means of reclassification with discriminant analysis. In a cluster analysis, patients with cluster headache showed the highest number (20%) of abnormalities, but also the highest percentage (13%) of completely normal results. Our findings--a cross section analysis of personality profiles--contradict many other MMPI-based studies.

Adolescent↗
PubMedDate not supplied

Intravenous acetylsalicylic acid inhibits central trigeminal neurons in the dorsal horn of the upper cervical spinal cord in the cat.

Acetylsalicylic acid (ASA) is one of the most commonly used substances in the treatment of headache and other pain syndromes. It is only recently that its efficacy in the treatment of acute attacks and in the prophylaxis of migraine has been proven in clinical trials. Various peripheral and central mechanisms have been proposed for the analgesic effects of acetylsalicylic acid and its mode of action in migraine. The possible actions of acetylsalicylic acid in migraine include local analgesic effects, changes in cerebral serotonin turnover, modulation of antinociceptive neurons in the hypothalamus and inhibition of the release of algogenic peptides during neurogenic inflammation. In this study trigeminal somatosensory evoked potentials and single unit activity of central trigeminal neurons in the dorsolateral C2 spinal cord were monitored during electrical stimulation of the superior sagittal sinus in the cat. Intravenous administration of the soluble acetylsalicylic salt (acetylsalicylic lysinate, 30 mg/kg) reduced the peak-to-peak amplitudes of somatosensory evoked potentials from 219 +/- 11 mV by 18% after 45 minutes and by 26% after 60 minutes. Naloxone injection (0.5 mg/kg and 1.5 mg/kg) did not reverse the inhibition caused by ASA. The probability of trigeminal cell tiring was reduced in 63% percent of the monitored single units. The effect was not mediated through naloxone-sensitive opioid receptors and was independent from ASA-induced peripheral blockade of neuropeptides during neurogenic inflammation. The non-steroidal anti-inflammatory agent ketorolac (0.4 mg/kg, IVI) a new cyclooxygenase inhibitor, also reduced the somatosensory evoked potentials by 30% following the same time course.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMedDate not supplied

Diagnostics of cervicogenic headache.

Cervicogenic headache (CH) is a clearly defined headache syndrome and can usually be differentiated from other unilateral headaches like cluster headache, chronic paroxysmal hemicrania (CPH) and hemicrania continua by a thorough history and neurological examination. Combinations of CH with other headaches like migraine, tension headache, combination headache and drug induced headache, that occur quite frequently, can complicate the diagnosis. In our own material of 5520 headache patients the prevalence of CH was 13.8% (763). Four hundred and thirty of these patients suffered from CH in combination with one or more other headaches.

Cervical Vertebrae↗