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)

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

We measured, by RIA methods, ictal and interictal levels of substance P (SP), calcitonin-gene related peptide (CGRP) and neurokinin A (NKA) in the plasma of 30 young migraine patients with aura (MPA) and 45 migraine patients without aura (MWA), and compared the results with those of 30 age-matched controls. There were no significant differences between the levels of these vasoactive peptides in the control group and the levels in both migraine groups studied in headache-free periods. An elevation of CGRP levels in plasma was found during attacks in MPA and, to a lesser extent, in MWA (p < 0.03 and p < 0.05, respectively). A significant increase in NKA levels was also demonstrated in the MPA and MWA groups (p < 0.02 and p < 0.04, respectively). These data suggest, although indirectly, that CGRP and NKA could be involved in the pathogenesis of migraine attacks in juvenile migraine patients.
Cephalalgia 1995 Oct
PMID:Vasoactive peptide levels in the plasma of young migraine patients with and without aura assessed both interictally and ictally. 853 90

The aim of the study was to compare the tolerance of synthetic salmon calcitonin applied in two different ways, intramuscularly or intranasally, in 50 patients with postmenopausal osteoporosis with bone fractures. Thirty patients were treated with calcitonin in intramuscular or subcutaneous injections, whereas in 20 cases calcitonin was applied in nasal spray. In the first group several side effects were observed, like nausea, vomiting, abdominal pains, skin rush, headaches, dropping blood pressure, symptoms of bronchial spasm. Finally in 13 cases it was necessary to stop calcitonin therapy. On the other hand the patients receiving calcitonin in nasal spray did not manifest any severe side effects.
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PMID:[Comparison of calcitonin tolerance after intramuscular or intranasal administration in treatment for postmenopausal osteoporosis]. 871 Nov 77

Human nasal mucosa biopsy samples were studied by biochemical and histological methods to determine whether the concentration of calcitonin gene-related peptide-like immunoreactivity (CGRP-LI) as a marker of sensory nerves was dependent on the activity of neutral endopeptidase-like enzyme (NEP-LE). Mucosal samples from the middle turbinate were obtained from 32 patients undergoing functional endoscopic nasal surgery for non-allergic chronic rhinosinusitis. The degree of symptoms related to nasal obstruction, rhinorrhea and headaches was recorded. The number of inflammatory cells in each biopsy sample was evaluated by conventional histopathological examination. CGRP-LI was measured by radioimmunoassay. The activity of NEP-LE was evaluated in vitro using [3H] Leu5-enkephalin as substrate. A good correlation was observed between increased concentrations of CGRP, abundant inflammatory cells and the intensity of symptoms (R2 = 0.80). A low activity of NEP-LE was associated with a high concentration of both inflammatory cells and CGRP, suggesting that NEP-LE activity was reduced during inflammation. These observations further support the hypothesis that reduced degradation of sensory neuropeptides could be involved in the pathophysiological mechanisms of non-specific chronic rhinosinusitis.
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PMID:Neutral endopeptidase activity and concentration of sensory neuropeptide in the human nasal mucosa. 871 87

The autonomic nervous function in patients with migraine was studied during headache free intervals. (I) Hemodynamic test. The following observations were made: (1) a decrease in overshoot in Valsalva's maneuver; (2) orthostatic hypotension; (3) low levels of plasma norepinephrine; (4) failure in elevation of the plasma norepinephrine level after head-up tilting; (5) dilatation of the pupils after instillation in the eyes of 1.25% epinephrine; (6) a long recovery time in test by bolus injection of l-norepinephrine. These data suggest that patients with migraine show sympathetic hypofunction together with denervation hypersensitivity of the iris and arteries. (II) Neuropeptides. Blood samples were taken after 30 minutes supine rest in a quiet room and the level of substance-P (SP), calcitonin gene-related peptide (CGRP), endothelin-1 (ET-1), and human atrial natriuretic peptide (hANP) were determined by radioimmunoassay. The level of SP, CGRP, and hANP in classic migraineurs during headache-free intervals were significantly lower than that of controls. There was no significant difference in the level of ET-1 between migraineurs and controls. These data suggest that neuropeptides such as SP, CGRP and hANP are closely related to the pathophysiology of migraine. (III) L-arginine infusion test. To examine whether or not NO is involved in the pathophysiology of migraine, L-arginine, a precursor of NO, was administered. The magnitude of blood pressure decrease in migraineurs was significantly greater than that of controls. Although plasma levels of CGRP decreased significantly in controls following L-arginine infusion, those of CGRP did not change in migraine patients. These data suggest that NO and CGRP may be involved in pathophysiology in migraine.
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PMID:[Autonomic nervous activity in migraine]. 875 90

The vasomotor effects of calcitonin gene-related peptide (CGRP) analogues have been studied in circular segments of fresh human cerebral arteries obtained at neurosurgical operations using a sensitive in vitro system. Human alpha-CGRP, human beta-CGRP, rat alpha-CGRP and rat beta-CGRP induced strong and potent relaxation of precontracted circular vessel segments. The Imax (maximum relaxant effect) to human calcitonin was low and the pD2 (concentration for half maximum effect) 7.7 was much lower than that of CGRP. The CGRP-1, antagonist human alpha-CGRP8-37 blocked the response to human alpha-CGRP but not to human beta-CGRP, while the putative antagonist [Tyr]CGRP28-37 did not. Capsaicin (10(-15)-10(-8)M) caused relaxation of the cerebral arteries by 22% of precontraction. Pre-treatment with 10(-6)M human alpha-CGRP8-37 inhibited this relaxation. Human alpha-CGRP increased the cyclic AMP content of human cerebral arteries in a concentration-dependent manner. This increase in adenylyl cyclase activity was blocked by human alpha-CGRP8-37. The results suggest that CGRP-1 receptors coupled to adenylyl cyclase are present in human cerebral arteries.
Cephalalgia 1996 Aug
PMID:Calcitonin gene-related peptide is released from capsaicin-sensitive nerve fibres and induces vasodilatation of human cerebral arteries concomitant with activation of adenylyl cyclase. 886 58

Chronic paroxysmal hemicrania (CPH) is a rare headache syndrome of short-lasting attacks of pain, characterized clinically by trigemino-parasympathetic activation. The features of the headache are severe attacks of pain that generally last no more than minutes in association with autonomic activation, such as lacrimation or rhinorrhea. We report a patient fulfilling International Headache Society guidelines for the diagnosis of CPH in whom levels of calcitonin gene-related peptide (CGRP) and vasoactive intestinal polypeptide (VIP) were elevated in the cranial circulation during attacks. Moreover, successful treatment of the problem with indomethacin leads to normalization of the levels of both CGRP and VIP. Given that similar neuropeptide changes are seen in cluster headache the data suggest a shared underlying pathophysiology between CPH and cluster headache.
Cephalalgia 1996 Oct
PMID:Neuropeptide changes in a case of chronic paroxysmal hemicrania--evidence for trigemino-parasympathetic activation. 890 56

The necrotizing lymphadenitis of Kikuchi-Fujimoto is an uncommon disease in Spain. In a review of the literature we found only five cases reported until 1995. We report here two patients with the diagnosis of this entity in an area hospital during a one-year period. This fact contrasts with the low frequency of this disease reported so far in our country. The cases were two young women who were investigated because of cervical lymph node enlargement and headache. The lymph node biopsy revealed typical findings of the necrotic phase of the Kikuchi-Fujimoto disease in one case; the histology in the other case was characteristic of the so called proliferative phase. The two patients evolved spontaneously with a favorable outcome. Lymph node enlargements resolved in less than three months. All microbiological investigations performed were negative. One of the two patients was receiving intranasal calcitonin when symptoms developed. The incidence of Kikuchi-Fujimoto disease might be higher than considered. The spontaneous resolution of the disease and the requirement of the histological examination for its diagnosis are factors limiting its identification.
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PMID:[Necrotizing histiocytic lymphadenitis (Kikuchi-Fujimoto disease): contribution of 2 cases]. 900 75

Nitroglycerine is known to induce a headache attack in cluster headache patients, which is indistinguishable from a spontaneous attack. It has recently been suggested that a release of calcitonin gene-related peptide (CGRP) from peripheral terminals of trigeminal nociceptive neurons, which supply cephalic blood vessels, underlies symptoms of cluster headache. The aim of this study was to investigate whether the provocative action of nitroglycerine in cluster headache is due, at least in part, to activation of the trigeminovascular system. Nineteen subjects suffering from episodic cluster headache participated in the study. Eleven of them were in an active period, whilst the others were in remission at the time of the study. CGRP-like immunoreactivity (CGRP-LI) was measured in blood samples from the extracerebral circulation before and after the sublingual administration of nitroglycerine. Baseline CGRP-LI plasma levels were higher (P < 0.05) in the patients who were in an active period. Only in these patients did nitroglycerine induce an attack, which was preceded by a latent period with a mean duration of 27 +/- 3 min. When compared with the baseline, a significant (P < 0.01) increase in plasma CGRP-LI was detected at the peak of the provoked attack; no such increase was detected during the latent period, or at the onset of the attack. The results of this study suggests that the provocative action of nitroglycerine in cluster headache is due, at least in part, to activation of the trigeminovascular system. This mechanism seems to be slow and unrelated to the well-known rapidly occurring vasodilator effects of the drug. Finally, activation of the trigeminovascular system only occurs in those patients already in an active cluster headache period who also have high basal CGRP-LI plasma levels. This suggests that a hyperactivity of trigeminal nociceptive fibres could make the trigeminovascular system of these patients sensitive to the triggering action of nitroglycerine.
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PMID:Responsiveness of the trigeminovascular system to nitroglycerine in cluster headache patients. 911 75

Primary Raynaud's phenomenon is common, particularly in younger women, and may be familial. Vasospasm is not confined to the digits and may involve, for example, the tongue and nose, and also visceral organs like the heart, oesophagus or lung and cerebral circulation. Symptoms tend to be milder in primary compared with secondary Raynaud's phenomenon, which is associated with other disorders such as the connective tissue diseases. Indeed, the severity of symptoms often acts as the predictor for the much later onset of the associated systemic disease. Occupational Raynaud's phenomenon is related to the use of vibrating instruments, and a significant proportion of patients may be cured by an early change in job. In those over 60 years of age, Raynaud's phenomenon is commonly a result of atherosclerotic obstructive arterial disease, and screening for and treatment of the risk factors is appropriate. The best-studied mechanisms in Raynaud's phenomenon involve the blood and vascular endothelium. Microcirculatory flow may be impeded by activated platelet clumps, rigid red and white blood cells and damaged endothelium. These platelet clumps, white blood cells and damaged endothelium also release vasoactive/vasoconstrictive compounds which may additionally trigger the clotting cascade and thrombosis. Initial management for mild disease should focus on support and advice regarding avoidance of known precipitating factors, including vasospastic drugs. Cold protection with warming agents, 'Abel' shoes and also electrically heated gloves and socks is effective, but may be too cumbersome and inconvenient for some patients. Simple vasodilators like naftidrofuryl, inositol nicotinate and possibly pentoxifylline (oxpentifylline) are useful in mild disease, with adverse effects like headache and flushing being less problematic. The 'gold standard' of Raynaud's phenomenon treatment is nifedipine, a calcium channel antagonist/blocker. Full dosage, however, can be limited by ankle swelling, headache and flushing, but adverse effects may be reduced by using the 'retard' or long-acting preparations. Adverse effects are also reduced with the newer calcium channel antagonists like diltiazem but at the expense of efficacy. Useful, enhanced benefit is also achieved by combination therapy with vasodilators. Newer treatments include the prostaglandin analogues which are effective but disadvantaged by their parenteral route of administration, and lack of licence in some countries. Oral preparations are, however, being studied and are in the pipeline. Essential fatty acid supplementation is mildly effective, while ketanserin and calcitonin gene-related peptide both look promising. Lumbar sympathectomy retains its important role in the treatment of Raynaud's phenomenon involving the lower limbs. Satisfactory symptomatic relief is now possible for many patients with Raynaud's phenomenon and this should certainly be the aim for all patients seeking medical help.
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PMID:Pharmacotherapy of Raynaud's phenomenon. 911 18


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