Experimental models for the study of cluster headache.
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Animals↗
Biomedical subjects
G Nappi
Publications and source records attributed to G Nappi.
Neurophysiological approach to the study of cluster headache.
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Blinking↗
The effects on the central nervous system of nitroglycerin--putative mechanisms and mediators.
Nitroglycerin is an organic nitrate that has been used as a vasodilator in the treatment of cardiac diseases for over a century. Only recently it has been demonstrated that the vasodilator effect of this drug depends upon the formation of nitric oxide in the blood vessel wall. However, clinical and research data gathered during the last decades have suggested that nitroglycerin possesses, besides its peripheral vasodilator effect, additional, puzzling biological activities. This organic nitrate compound provokes reflex cardiovascular activities via its interaction with the central sympathetic system. Its cerebrovascular effect, on the other hand, is probably mediated by the local release of neuropeptides. The direct application of nitroglycerin onto brain nuclei causes a prompt increase in the neuronal discharge rate. From a neurological point of view, nitroglycerin consistently induces a specific headache attack in patients suffering from migraine. Because of its temporal pattern and clinical characteristics, nitroglycerin-induced headache cannot be solely ascribed to the a drug-induced vasorelaxation. The demonstration that systemic nitroglycerin administration activates a widespread set of vegetative, nociceptive and neuroendocrine structures in the central nervous system seems to further support the occurrence of central mechanisms in the biological activity of nitroglycerin. Double labeling immunocytochemical and neuropharmacological studies have provided information on the putative neurotransmitters and neurochemical mechanisms involved in nitroglycerin-induced neuronal activation.
Animals↗
Peripheral markers of oxidative stress in Parkinson's disease. The role of L-DOPA.
Oxidative stress plays a central role in the pathogenesis of Parkinson's disease (PD). L-DOPA, the gold standard in PD therapy, may paradoxically contribute to the progression of the disease because of its pro-oxidant properties. The issue, however, is controversial. In this study, we evaluated peripheral markers of oxidative stress in normal subjects, untreated PD patients and PD patients treated only with L-DOPA. We also measured platelet and plasma levels of L-DOPA, 3-O-methyldopa (the long-lasting metabolite of the drug), and dopamine. We found that isolated platelets of treated PD patients form higher amounts of 2,3-dihydroxybenzoate, an index of hydroxyl radical generation, than platelets of controls or untreated patients. In treated patients, platelet levels of 2,3-dihydroxybenzoate were positively correlated with platelet levels of L-DOPA, 3-O-methyldopa, and with the score of disease severity. Disease severity was correlated with platelet and plasma levels of L-DOPA, as well as with the daily intake of the drug. No significant differences in platelet levels of cytosolic and mitochondrial isoforms of the antioxidant enzyme superoxide dismutase were found between PD patients, either treated or untreated, and controls. Our findings lend further support to the hypothesis that L-DOPA might promote free radical formation in PD patients.
Antiparkinson Agents↗
An Italian-Australian comparison of quality of life among people with intellectual disability living in the community.
This paper reports the measurement of both objective and subjective quality of life in samples of people either with intellectual disability or from the general adult population, drawn from Australia and Italy. Measures were made using the Comprehensive Quality of Life Scale. Generally, it was found that the scores for all groups were comparable. This finding is consistent with the provision of generally decent objective living conditions in both countries and subjective well-being homeostasis, wherein subjective quality of life is held within a predictable range. These results are discussed in the context of measurement difficulties imposed by the need for simple Likert scales and subjective data which are strongly negatively skewed.
Adult↗
Unbalanced randomization influences placebo response: scientific versus ethical issues around the use of placebo in migraine trials.
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Double-Blind Method↗
Psychiatric comorbidity and psychosocial stress in patients with tension-type headache from headache centers in Italy. The Italian Collaborative Group for the Study of Psychopathological Factors in Primary Headaches.
A multicenter study was carried out in 10 Italian Headache Centers to investigate the prevalence of psychosocial stress and psychiatric disorders listed by the IHS classification as the "most likely causative factors" of tension-type headache (TTH). Two hundred and seventeen TTH adult outpatients consecutively recruited underwent a structured psychiatric interview (CIDI-c). The assessment of psychosocial stress events was carried out using an ad hoc questionnaire. The psychiatric disorders that we included in the three psychiatric items of the fourth digit of the IHS classification were depressive disorders for the item depression, anxiety disorders for the item anxiety, and somatoform disorders for the item headache as a delusion or an idea. Diagnoses were made according to DSM-III-R criteria. At least one psychosocial stress event or a psychiatric disorder was detected in 84.8% of the patients. Prevalence of psychiatric comorbidity was 52.5% for anxiety, 36.4% for depression, and 21.7% for headache as a delusion or an idea. Psychosocial stress was found in 29.5% of the patients and did not differ between patients with and without psychiatric comorbidity. Generalized anxiety disorder (83.3%) and dysthymia (45.6%) were the most frequent disorders within their respective psychiatric group. The high prevalence of psychiatric disorders observed in this wide sample of patients emphasizes the need for a systematic investigation of psychiatric comorbidity aimed at a more comprehensive and appropriate clinical management of TTH patients.
Adult↗
Chronic daily headache. How should it be included in the IHS classification?
A number of patients attending specialty headache centers complain of very frequent, almost continuous or continuous headaches, which are usually grouped together under the term chronic daily headache, a category which does not appear in the International Headache Society (IHS) classification. On the basis of the IHS criteria, these patients can only be classified as having a chronic tension-type headache with the possible addition of migraine, if migrainous attacks are superimposed on the "background" headache. However, several studies have demonstrated that most patients with chronic daily headache originally suffered from migraine and that their migraine has transformed, in the course of time, into a chronic headache picture in which isolated migraine attacks may or may not persist. Despite some differences in the personal opinions of authors involved in the care of patients with chronic daily headache, some views seem to be generally accepted: (1) the great majority of chronic daily headaches are transformations of an original episodic migraine and cannot be included in the chronic tension-type headache category, (2) the current IHS classification does not allow many patients presenting with chronic daily headache to be classified correctly, (3) an important nosological category (transformed migraine) has emerged from all the studies on this subject, (4) it is impossible to diagnose transformed migraine merely by "photographing" the picture of single attacks. Although some theoretical problems remain unresolved, it seems to us that the next revision of the IHS classification can no longer ignore the existence of chronic daily headache.
Headache Disorders↗
Modifications of local cerebral metabolic rates for glucose and motor behavior in rats with unilateral lesion of the subthalamic nucleus.
Inactivation of the subthalamic nucleus (STN) has attracted interest as a therapeutic tool in Parkinson's disease. The functional consequences of the inactivation, however, are uncertain. In this study definition of the pattern of changes of cerebral functional activity associated with lesion of the STN and dopaminergic stimulation, by using the [14C]deoxyglucose method, was sought. Six or 7 days following unilateral lesion of the STN, the animals were divided into two groups: One group (n = 10) was administered apomorphine (1 mg/kg) subcutaneously; the second group (n = 10) received saline. The [14C]deoxyglucose procedure was initiated 10 minutes following the drug or saline injection. The results show that systemic administration of apomorphine to rats with unilateral lesion of the STN causes ipsiversive rotational behavior and asymmetries of glucose utilization of defined brain areas, including the substantia nigra reticulata, globus pallidus, and entopeduncular nucleus. These nuclei are the main targets of the subthalamic excitatory projections. Lesion of the nucleus per se (without challenge with apomorphine) has no significant consequences on glucose utilization. The findings indicate that the STN is involved in the activation of the basal ganglia output nuclei induced by systemic dopaminergic stimulation.
Animals↗
Bromocriptine test in the evaluation of patients with syncope of unknown aetiology. A case-control study.
The aim of the present study was to evaluate, through a case-control study, the specificity of the upright tilt test with bromocriptine as a marker of neurally mediated syncope of unknown aetiology. We have compared upright tilt test with bromocriptine (2.5 mg p.o.) in patients with syncope of unknown aetiology and controls. A total of 23 patients and controls matched by age and sex had upright tilt test with bromocriptine. The upright tilt test procedure consisted of 10 min in supine position, 10 min of 60 degree head-up tilt and a further 10 min with the subject supine; this procedure was performed in baseline condition and 60, 120, 180 and 240 min after the administration of bromocriptine. The protocol end points were the development of syncope or presyncope in association with hypotension with or without bradycardia. A positive response to bromocriptine test was found in 78% (95% CI, 61% to 95%) of patients and in 13% (95% CI, 0% to 26%) of controls (P<0.001). No significant differences were detectable among patients and controls showing a positive response to the test. Bromocriptine test seems to be a useful alternative tool for the diagnosis of neuromediated syncope also suggesting that dopaminergic supersensitivity may, at various and to varying degrees, play a role in the pathogenesis of syncopal episodes.
Adolescent↗
Memory functioning at menopause: impact of age in ovariectomized women.
Estrogens are known to act selectively on some components of memory, exerting beneficial effects on cognitive performances. However, there are few data on the long-term effect of the lack of estrogen in postmenopausal women. Therefore, we investigated attentive and verbal memory performances in physiological and surgical menopause, drawing attention to the impact of age at menopause, and we compared a well-known aging and estrogen-dependent index, the entity of bone mass loss to memory functioning. No significant differences were found in the mean scores of attentive and psychomotor performances between physiological and surgical menopause, whereas a lower number of recalled words (recency effect = PS2) was found in surgical menopause (p < 0.001) in comparison to physiological menopause. In addition, both the age at the time of ovariectomy (r = 0.47; p = 0. 014) and the years since surgery (r = -0.64; p = 0.000) correlated to short-term verbal memory performance (PS2) with better scores when surgery occurred later in women's lives. Surgical menopause is able to affect short-term verbal memory more than physiological menopause and seems to represent a critical negative event within the female brain, in particular when it occurs prematurely.
Adult↗
Hydroxyl radical production in the substantia nigra after 6-hydroxydopamine and hypoxia-reoxygenation.
To study the involvement of oxidative stress in 6-OHDA neurotoxicity, we investigated the production of the hydroxyl free radical (OH.) in the substantia nigra (SN) and the striatum (CS) several moments after intranigral injection of the neurotoxin, with or without an added episode of hypoxia (30 min, 95% N2, 5% O2). We utilized the hydroxylation of salicylate to 2,3 dihydroxybenzoic acid (2,3 DHBA) as indication of OH. production. When 2.3 DHBA levels were not modified, the levels of 2,5 DHBA were taken as an indication of cytochrome P450 (CYP 450) metabolism. 6-OHDA alone did not increase the production of 2,3 DHBA in the SN. 2,5 DHBA increased significantly after 120 min and was high up to 24 h. An episode of hypoxia (60 min after 6-OHDA injection) significantly worsened the decrease of dopamine (DA) in the striatum assessed 8 days after injection of 6-OHDA in the SN. Hypoxia performed 60 min and 24 h before or 24 h after 6-OHDA did not show any additional effect on striatal DA levels. Contrary to results obtained after 6-OHDA alone, 2,3 DHBA increased significantly 120 min after the injection, when the hypoxia-reoxygenation was added to the 6-OHDA treatment. Our data are showing a relationship between the increase in OH. production and a concomitant worsening of neuronal degeneration. As a whole, the results support the idea that neurons undergoing 6-OHDA neurotoxicity have their antioxidant defences affected and that oxidative stress is actually an important eliciting factor in 6-OHDA dependant neurodegeneration. However, OH. may not be the main radical species involved in this process. Additionally, 6-OHDA also appeared to provoke a long-term increase in CYP 450 activity.
3,4-Dihydroxyphenylacetic Acid↗
Endotoxin stimulates an endogenous pathway regulating corticotropin-releasing hormone and vasopressin release involving the generation of nitric oxide and carbon monoxide.
Although the administration of endotoxin in vivo activates the neuroendocrine stress axis in the process of crosstalk between the immune and endocrine axes, the direct application of endotoxin to the hypothalamus in vitro does not stimulate the release of the hypothalamic peptides controlling the hypothalamo-pituitary-adrenal (HPA) axis, corticotropin-releasing hormone (CRH) and vasopressin. The hypothesis has therefore been tested that endotoxin may also activate inhibitory pathways, specifically those involving the generation of nitric oxide (NO) and carbon monoxide (CO). Studies were performed on the isolated rat hypothalamus using endotoxin in the presence or absence of inhibitors of heme oxygenase (which generates CO) and nitric oxide synthase, and ferrous hemoglobin. Endotoxin alone decreased both CRH and vasopressin secretion from the hypothalamus. However, when applied together with a nitric oxide synthase inhibitor, the inhibitory effect on CRH was lost. Conversely, co-administration with heme oxygenase inhibitors transformed the inhibition of vasopressin to stimulation, while having no effect on the inhibition of CRH. Ferrous hemoglobin reversed the inhibition of vasopressin, but did not lead to stimulation. It is therefore concluded that endotoxin may stimulate endogenous pathways that lead to the generation of NO, which in turn inhibits CRH. In addition, it generates CO, which modulates the release of vasopressin. These gases are thus potential counter-regulatory controls to the activation of the HPA.
Animals↗
Quantitative study of mitochondrial complex I in platelets of parkinsonian patients.
Activity of mitochondrial enzyme complex I (NADH-ubiquinone oxidoreductase) is reduced in the substantia nigra of patients with Parkinson's disease (PD). A less pronounced decrease in the activity of this enzyme has also been reported in platelets of PD patients. To obtain quantitative information on platelet complex I in PD, we studied platelet complex I in 16 PD patients and 16 age-matched controls by using a newly developed technique based on the binding of [3H]dihydrorotenone ([3H]DHR), an analog of the pesticide rotenone, to complex I. We also investigated the inhibitory effect of MPP+ (1-methyl-4-phenyl-pyridinium) on [3H]DHR specific binding to platelet complex I. PD patients and controls showed similar levels of [3H]DHR specific binding; preincubation of platelets with MPP+ caused the same degree of inhibition of [3H]DHR specific binding in the two groups. In PD patients, we observed a direct correlation between MPP+-induced inhibition of [3H]DHR specific binding and the daily intake of levodopa, which may be related to drug-induced changes in the transport of MPP+ into the platelet or in its binding to complex I. These findings demonstrate that the reported reduction in complex I activity in platelets of PD patients can not be accounted for by an abnormality at the level of the rotenone binding site (putatively the ND-1 gene product), although they do not exclude differences in complex I activity between PD patients and controls.
1-Methyl-4-phenylpyridinium↗
Indomethacin increases the effect of isosorbide dinitrate on cerebral hemodynamic in migraine patients: pathogenetic and therapeutic implications.
Intracerebral vascular reactivity induced by the nitric oxide (NO) donor isosorbide dinitrate (IDN, 5 mg sublingually) is more major and longer-lasting in migraine patients who develop delayed headache in response to the drug. The headache is purportedly due to neuronally-mediated vascular mechanisms. Indomethacin inhibits prostaglandin synthesis, which is involved in NO generation. Indomethacin also decreases cerebral blood flow by constricting precapillary resistance vessels. In the present study, the hemodynamic effects of indomethacin were evaluated in migraine patients and healthy controls by means of transcranial Doppler monitoring. Indomethacin caused a significant decrease in mean flow velocity in the middle cerebral artery. This was an additional effect to the mean velocity decrease induced by IDN. The interactions between the two drugs suggest that their effects on cerebral hemodynamics (and pain) may be of relevance both in understanding the role of NO in migraine pathogenesis and in evaluating symptomatic treatments for migraine attacks.
Adult↗
Combined evaluation of pupillary and cardiovascular responses to cold pressor test in cluster headache patients.
Little is known about the structures and mechanisms involved in the pathophysiology of cluster headache (CH). In this study, pupillary and cardiovascular responses to the cold pressor test (CPT) were monitored in CH patients during either an active phase of disease or a remission period in order to evaluate the oculocephalic and cardiovascular functioning of the autonomic nervous system in this form of idiopathic headache. CH patients showed a specific pattern of pupillary response on both sides during both phases of the disease. This response differed from that of controls because of an absent miosis. The pressor response to CPT was more marked in CH patients than in controls. Naloxone pretreatment caused specific and selective changes in both the pupillary and cardiovascular responses of CH patients. These data suggest a systemic sympathetic hyperactivation in response to CPT in CH patients. An oculocephalic sympathetic hypofunction is possibly associated as well as an altered opioid neuromodulation.
Adult↗
Premenstrual syndrome and anxiety disorders: a psychobiological link.
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Anxiety Disorders↗
Cerebral hemodynamics in primary headaches: the transcranial Doppler experience.
This paper is an extensive review of the use of transcranial Doppler (TCD) devices in "vascular" forms of headache, and a discussion of the possible occurrence of nonunivocal results, particularly in migraine with or without aura. Despite the large variability in findings, TCD is a noninvasive, safe, and reproducible method for studying hemodynamic phenomena which characterize the clinical profile of migraine and cluster headache attacks. Similarly, it can detect cerebrovasomotor reactivity to external/internal environmental stimuli, as well as responses to pharmacological (therapeutic or diagnostic) agents. Possible future applications of TCD in monitoring vasomotor changes in response to selective stimuli (sympathetic, neuropeptidergic, etc.) are also considered.
Cerebrovascular Circulation↗