Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018681 (headache)
 56,091 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Neuropeptide Y (NPY) is widely distributed throughout sympathetic nerve endings where it is co-stored and co-secreted with noradrenaline. It is considered a marker of noradrenergic function. To determine the role of NPY in the pathogenesis of juvenile headache, we determined its plasma levels in two groups of young migraine patients (with and without aura), in a group of episodic tension-type headache patients and in a group of age and sex-matched healthy subjects. Significantly lower plasma levels of NPY were evident in the migraine patients with aura (P < 0.001) and, to a lesser extent, in the migraine patients without aura (P < 0.02), both assessed in the interictal period, with respect to the control group. Plasma NPY levels tended to significantly increase during attacks in migraine patients with aura (P < 0.0009). A less evident, though significant increase was also present during attacks in migraine patients without aura (P < 0.02). No significant variations were observed between headache-free periods and attacks in tension-type headache patients. Reduced NPY levels in the interictal period can be considered further evidence of the derangement of the sympathetic function in the course of migraine, particularly that with aura. The increase in NPY levels during migraine attacks could be an expression of sympathetic activation, even though the functional status of this system is less efficient.
Headache 1994 Jan
PMID:Neuropeptide Y in juvenile migraine and tension-type headache. 813 38

Six healthy males, the EMSInauts, were isolated in hyperbaric chambers for a period of 28 days at 5-msw overpressure. During that period they had to carry out meaningful operational and research tasks in addition to monitoring their psychological and physiological reactions. The actual workload was evaluated and compared with the planned workload, and its effects on symptomatology and psychobiology. The perceived workload and its effects on psychosomatic symptomatology and on some biological indices were monitored. Thus it was possible to evaluate how the workload carried during 4 weeks of isolation affected the psychological and biological well-being of the six EMSInauts. The following three types of assessments were performed: 1. Workload assessment: The objective workload was calculated based on the schedule which was revised daily, and the actual load calculated by the commander. A workload questionnaire was administered daily after each working session. 2. Psychosomatic assessment: Morning and evening questionnaires were administered daily. The state of health and of anxiety were also evaluated. 3. Biological indices: Cortisol, testosterone, adrenalin, and noradrenaline were determined once a week. In addition, cardiac activity was monitored every day. The workload assessment showed that on the average the planned workload was accomplished in slightly less than the scheduled time. The workload was not perceived as severe in terms of cognitive, emotional, and physical load. The group rated the support received from each other and from the mission control personnel as average, with minor changes during the isolation period. They gave a high rating to the amount of control they had over their activities. Fatigue and tension were scored in the middle range. The psychosomatic assessment showed that there were few symptoms, and these were mostly of low severity. The most common symptom was general fatigue. Furthermore, minor dizziness, headache and light tremor was in some cases reported. The sleep quality was good, but complaints about poor sleep increased somewhat with the passing of time. Few and mostly minor health problems were experienced during isolation. Only one EMSInaut had to miss one day of work due to a bout of flu. The state of anxiety was below that of the general population throughout the isolation period. The biological indices used showed no evidence of stress from the workload handled during the isolation period. The level of the "stress hormone" cortisol actually decreased during isolation. The adrenalin excretion, which tends to go up during acute stress, remained unchanged during this period. Neither was there any evidence of changes in cardiac activity throughout the isolation period.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:European isolation and confinement study. Workload and stress: effects on psychosomatic and psychobiological reaction patterns. 816 54

The venoconstrictive activity of sumatriptan and its interaction with noradrenaline (NA)- and 5-hydroxytryptamine (5HT) venoconstriction was studied in vivo in the hand vein of migraineurs. Sumatriptan, injected at increasing doses into the vein, caused local venoconstriction after a 500 microgram dose, comparable to that induced by 0.5-1 micrograms of 5HT. This venoconstriction was completely inhibited by low doses of ketanserin (5 micrograms). Subcutaneous sumatriptan (6 mg) provoked a minor increase in vein tone, lasting less than 30 min. Non-venoconstrictive doses of sumatriptan (10-100 micrograms), injected in the hand vein, produced an amplification of NA-venoconstriction but not of 5HT-induced venoconstriction. A similar increased effect was displayed by subcutaneous sumatriptan (6 mg) for at least 1 h. Sumatriptan appears to cause peripheral venoconstriction only at high doses locally applied (in the hand vein), by acting on 5HT2 receptors. Clinical subcutaneous doses (6 mg) do not show significant venoconstrictive effects. The amplifying effect on NA venoconstriction, also caused by 5HT, ergotamine and dihydroergotamine in human cranial arteries, may be important in explaining the therapeutic action of sumatriptan in migraine attacks.
Cephalalgia 1993 Dec
PMID:Amplifying effect of sumatriptan on noradrenaline venoconstriction in migraine patients. 831 46

The biochemical features of two patients with phaeochromocytomas illustrate the inadvisability of depending on a single group of analytes for the diagnosis. The first case presented as a surgical emergency with retroperitoneal haemorrhage. Biochemical diagnosis was difficult since total 24 hour urinary free catecholamine excretion was within normal limits in two out of three samples, and only marginally raised in the third with an atypical preponderance of adrenaline. Plasma catecholamine concentrations were also normal. But urinary excretion of the catecholamine metabolites, metadrenaline and 4-hydroxy-3-methoxy mandelic acid (HMMA), was consistently raised. In contrast, the second patient presenting with headache and labile hypertension showed normal metabolite excretion in the face of grossly increased free noradrenaline excretion and raised plasma noradrenaline concentrations. It is therefore recommend that, as well as urinary free catecholamines, one group of their main metabolites, the 3-methoxy amines (normetadrenaline and metadrenaline) or HMMA, should routinely be measured whenever a phaeochromocytoma is suspected.
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PMID:Biochemical diagnosis of phaeochromocytoma: two instructive case reports. 846 26

The functional role of the trigeminal system has been addressed in experiments on the cortical surface of alpha-chloralose anaesthetized cats. Application of calcitonin gene-related peptide (CGRP) caused a concentration-dependent increase in arteriolar calibre by 38 +/- 5% (n = 8) with an IC50 of 2 nM. Cerebral veins did not relax upon CGRP administration (n = 12). Substance P (SP) was less potent but showed dilatation of both arterioles (21 +/- 4%) and veins (16 +/- 4%). The cerebrovascular trigeminal system was investigated after chronic (14 days) surgical lesion of the trigeminal nerve with the concomitant disappearance of perivascular CGRP/SP immunoreactive nerves. The cortical arteriolar responses to subarachnoid microinjections of acidic (pH 6.8) and basic CSF (pH 7.6) as well as noradrenaline (10(-4) M), neuropeptide Y (10(-7) M), prostaglandin F2x (10(-6 M), barium chloride (10(-4) M), and autologous blood (5 microl) were examined in anaesthetized cats with lesions of the trigeminal nerve, and were compared with their effects in sham-operated animals. The magnitude of the vasodilator and vasoconstrictor responses to these agents was unaffected by trigeminal lesions. However, duration of the vasoconstriction produced by basic CSF, but not the vasodilitation to acidic CSF, was markedly prolonged by trigeminal lesions (from 0.8 +/- 0.1 min to 2.2 +/- 0.3 min, p < 0.01). Also, the vasoconstrictor responses to noradrenaline, prostaglandin F2x, barium chloride, and autologous blood were significantly prolonged, while the maximum contractile effect to each agent was similar in lesioned as in sham-operated controls. The effects of CGRP, SP, and neurokinin A (NKA) have been examined on isolated cerebral arteries in vitro. Different CGRP analogues induced a strong relaxation with no difference in Imax (85-96%) or pD2 values (8.65 - 9.12). NKA induced a stronger relaxation than SP (Imax: 33% and 13%, respectively). SP was more potent than NKA (pD2:8.7 and 7.7, respectively). Capsaicin, a substance which selectively causes the release of stored sensory neuropeptides (CGRP, SP, NKA), caused in vitro relaxation of precontracted arteries. This relaxation was not affected by the neurokinin blocker spantide, but shifted towards higher capsaicin concentrations by the CGRP antagonist (CGRP 8-37. Thus, in this preparation CGRP rather than a neurokinin (SP/NKA) is responsible for the capsaicin-induced dilatations.
Cephalalgia 1995 Oct
PMID:Modification of vasoconstrictor responses in cerebral blood vessels by lesioning of the trigeminal nerve: possible involvement of CGRP. 853 89

Some clinical as well as pharmacological indications seem to suggest that a reduction of the noradrenergic tone occurs in cluster headache (CH), during both the active and remission periods. But sharp fluctuations of the sympathetic system may trigger the attacks. Clonidine, an alpha-2-adrenergic presynaptic agonist, regulates the sympathetic tone in the central nervous system. Therefore, a continuous administration of low-dose clonidine could be potentially beneficial in the active phase of CH by antagonizing the variations in noradrenergic tone. After a run-in week, we administered transdermal clonidine (5 - 7.5 mg) for one week to 13 patients suffering from CH, either episodic (8 cases) or chronic (5 cases). During clonidine treatment, the mean weekly frequency of attacks dropped from 17.7 +/- 7.0 to 8.7 +/- 6.6 (p = 0.0005), the pain intensity of attacks measured on the visual analogue scale from 98.0 +/- 7.2 to 41.1 +/- 36.1 mm (p = 0.001), and the duration from 59.3 +/- 21.9 to 34.3 +/- 24.6 min (p = 0.02). This open pilot study strongly suggests that transdermal clonidine may be an effective drug in the preventive treatment of CH. Its efficacy is possibly due to its central sympatho-inhibition, which reduces or prevents the occurrence of fluctuations of noradrenaline release that may induce the attacks.
Cephalalgia 1995 Oct
PMID:Efficacy of transdermal clonidine in short-term treatment of cluster headache: a pilot study. 920 77

The physiology and pharmacology of the middle meningeal artery was investigated in cats in order to determine whether this artery was subject to normal neural and humoral control mechanisms. Carotid and middle meningeal arterial blood flows and resistances were measured in 16 cats anaesthetized with chloralose. The cervical sympathetic nerves were stimulated electrically. Stimulation of the cervical sympathetic nerves pre-ganglionically reduced blood flow in the middle meningeal artery by producing vasoconstriction in its resistance bed. The vasoconstriction was mediated via catecholamine-containing nerves, as it was abolished by prior intravenous administration of bretylium. Intravenous injections of noradrenaline or adrenaline also produced vasoconstriction in the middle meningeal arterial bed. 5-Hydroxytryptamine (5HT), on the other hand, produced a dilatation in the middle meningeal artery. We conclude that neurally or humorally released catecholamines can provide a plausible mechanism for vasoconstriction in the middle meningeal artery. The dilator effect of 5HT contrasts with the constrictor effect of the 5HT1-like receptor agonist sumatriptan and suggests a complex 5HT receptor pharmacology for the artery.
Cephalalgia 1996 Feb
PMID:Reactions of the middle meningeal artery of the cat to neural and humoral stimulation. 882 96

Although reflexes in human jaw muscles have been extensively studied, the neurotransmitters involved in the regulation of these reflexes are not well known. The aim of the present study was to investigate whether amitriptyline, a combined serotonin and noradrenaline re-uptake inhibitor, modulates the late exteroceptive suppression period (ES2) of temporal muscle activity in chronic tension-type headache. ES2 was recorded with a previously evaluated method and assessed by a blinded observer in 35 patients with chronic tension-type headache. Thereafter, ES2 was recorded in 27 of these patients during a double-blind, placebo-controlled, 3-way crossover trial investigating the prophylactic effect of amitriptyline, the selective serotonin re-uptake inhibitor citalopram, and placebo. ES2 duration was significantly shorter during treatment with amitriptyline than during placebo, P = 0.02, while ES2 duration only tended to be shorter during treatment with citalopram, P = 0.34. ES2 was not significantly correlated to the prophylactic effect of amitriptyline or to a range of clinical and experimental pain parameters. Our results demonstrate that amitriptyline reduces ES2 and indicate that ES2 is modulated by serotonergic as well as noradrenergic neuronal pathways.
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PMID:Amitriptyline, a combined serotonin and noradrenaline re-uptake inhibitor, reduces exteroceptive suppression of temporal muscle activity in patients with chronic tension-type headache. 891 95

In drug development the move from tricyclic antidepressants (TCAs) to selective serotonin reuptake inhibitors (SSRIs) involved not only the loss of the direct receptor interactions responsible for the adverse side effects of TCAs, but also the ability to inhibit the reuptake of noradrenaline. Selectivity for the single neurotransmitter, serotonin, may explain why SSRIs tend to be less efficacious than the TCAs, especially in more serious forms of depression. The advent of selective serotonin and noradrenaline reuptake inhibitors (SNRIs) has tended to confirm the idea that an action on both monoamine systems is important for maximal antidepressant efficacy. This paper reviews clinical trials comparing the new SNRI milnacipran with the SSRIs fluoxetine and fluvoxamine. A meta-analysis of the principal trials shows greater response rates (the proportion of patients with a decrease in symptom scores of 50% or more) with milnacipran (50 mg twice a day) than with fluoxetine (20 mg once a day), or fluvoxamine (100 mg twice a day) (milnacipran: 64%; SSRIs: 50%). Remission rates (the proportion of patients with Hamilton Depression Rating Scores of 7 or below) were also higher with milnacipran than with SSRIs (39 versus 28%). In one study, in which 100 mg milnacipran was given once a day in the evening, the higher response rate obtained with fluoxetine appears to be largely attributable to an inappropriate milnacipran dosage regimen. Data from a pharmacovigilance database including all patients participating in clinical trials with milnacipran (n = 5732) showed that, compared with the SSRIs, milnacipran produced fewer gastrointestinal side effects, such as nausea, and less anxiety. Milnacipran was, however, associated with a higher incidence of headache, dry mouth and dysuria. The results of these studies suggest that milnacipran is superior in efficacy to SSRIs and is equally well tolerated. Milnacipran, therefore, appears to offer a therapeutic advantage over the SSRIs.
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PMID:Milnacipran and selective serotonin reuptake inhibitors in major depression. 892 26

We retrospectively evaluated our experience with phaeochromocytoma from January 1986 to December 1995. There were 18 patients with surgically-proven phaeochromocytoma: three males, 15 females, aged 12-81 years (mean 42 years) at diagnosis. Sixteen were hypertensive; only 6/18 presented with two or more of the classical triad of headaches, palpitations and diaphoresis. One patient presented with hypertensive crisis. Duration of symptoms prior to diagnosis was 2 weeks to 6 years, mean 16.4 months. Sixteen patients had adrenal tumours and two had extra-adrenal tumours or paragangliomas. One had bilateral adrenal tumours and two had a combination of both adrenal and extra-adrenal tumours. There were four familial cases: two had multiple endocrine neoplasia type IIA (MEN-IIA), one had neurofibromatosis type I (NF-I) and one von Hippel-Lindau (VHL) disease. One patient had Cushing's syndrome arising from ectopic production of adrenocorticotropic hormone (ACTH) by the phaeochromocytoma. Disease was recurrent in three patients. Pre-operative diagnosis was confirmed mainly by elevated urine vanillylmandelic acid (VMA) and/or catecholamine levels. Twelve patients had plasma catecholamine determinations: noradrenaline was elevated in all, adrenaline in six and dopamine in two. Pre-operative localization was by CT scan or MR imaging in all patients. At follow-up of 1-10 years (median 4.8 years), 15 patients were cured surgically while two were asymptomatic despite recurrence of disease. One patient with recurrent paragangliomas died post-operatively.
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PMID:Phaeochromocytoma: a ten-year survey. 909 89


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