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Query: UMLS:C0018681 (headache)
 56,091 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The molecular mechanisms of migraine have not been fully clarified yet. Increased nitrosative and oxidative stress may be associated with migraine attacks. Platelets may play an important role in migraine patients and they can reflect the lability of tissues to nitrosative/oxidative stress. In the present study, we aimed to determine the levels of nitrosative and oxidative stress markers in platelets of migraine patients during headache-free and attack periods. A total of 56 subjects (22 migraine without aura, 14 migraine with aura, and 20 age- and sex-matched healthy controls) were included in the study and nitric oxide (NO) metabolites, malondialdehyde (MDA), and thiol (SH) groups were measured in platelets. During migraine attacks, platelet levels of nitrate, nitrite and MDA were significantly higher in migraineurs than these in control subjects (p = 0.042, p = 0.005 and p = 0.042, respectively). By contrast, during headache-free period, no statistically significant differences were found in the platelet levels of nitrate, nitrite and MDA between migraineurs and controls (p > 0.05), although the marginal increases were detected in migraineurs. These results suggest that increased biomarkers of nitrosative and oxidative stress in platelets may be important in migraine patients, especially during attacks; increase of NO metabolites in platelets during attacks supports the opinion that NO may play a modulatory role in biological processes particularly by vasodilatation in migraine attacks. Therefore, MDA and NO metabolites may serve as useful markers to show the increased vulnerability to nitrosative and oxidative stress in migraine patients.
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PMID:Increased nitrosative and oxidative stress in platelets of migraine patients. 1720 69

Up to 60 million people working indoors experience symptoms such as eye, nose and throat irritation, headache, and fatigue. Investigations into these complaints have ascribed the effects to volatile organic compounds (VOCs) emitted from building materials, cleaning formulations, or other consumer products. New compounds can result when the VOCs react with hydroxyl or nitrate radicals or ozone present in indoor environments. Several oxygenated organic compounds, such as glyoxal, methylglyoxal, glycolaldehyde, and diacetyl, have been identified as possible reaction products of indoor environment chemistry. Although research has previously identified diacetyl and glyoxal as sensitizers, additional experiments were conducted in these studies to further classify their sensitization potential. Sensitization potential of these four compounds was assessed using quantitative structure-activity relationship (QSAR) programs. Derek for Windows and National Institute for Occupational Safety and Health logistic regression predicted all compounds to be sensitizers, while TOPKAT 6.2 predicted all compounds except for methylglyoxal. All compounds were tested in a combined irritancy and local lymph node assay (LLNA). All compounds except for glyoxal were found to be irritants and all tested positive in the LLNA with EC3 values ranging from 0.42 to 1.9%. Methylglyoxal significantly increased both the B220(+) and IgE(+)B220(+) cell populations in the draining lymph nodes and total serum IgE levels. The four compounds generated by indoor air chemistry were predicted by QSAR and animal modeling to be sensitizers, with the potential for methylglyoxal to induce IgE. The identification of these compounds as sensitizers may help to explain some of the health effects associated with indoor air complaints.
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PMID:Evaluation of the contact and respiratory sensitization potential of volatile organic compounds generated by simulated indoor air chemistry. 2485 18

Nitrates are potent venous dilators and anti-ischemic agents. They are widely used for the relief of chest pain and pulmonary congestion in patients with acute coronary syndromes and heart failure. Nitrates, however, do not reduce mortality in patients with acute coronary syndromes. Combination of nitrates and hydralazine when given in addition to beta-blockers and angiotensin-converting enzyme (ACE) inhibitors reduce mortality and heart failure hospitalizations in patients with heart failure due to left ventricular systolic dysfunction who are of African-American origin. Side effects during nitrate therapy are common but are less well described in the literature compared with the reported side effects in patients with stable angina pectoris. The reported incidence of side effects varies highly among different studies and among various disease states. Headache is the most commonly reported side effect with an incidence of 12% in acute heart failure, 41-73% in chronic heart failure, 3-19% in unstable angina and 2-26% in acute myocardial infarction. The reported incidence of hypotension also differs: 5-10% in acute heart failure, 20% in chronic heart failure, 9% in unstable angina and < 1-48% in acute myocardial infarction, with the incidence being much higher with concomitant nitrate therapy plus angiotensin-converting enzyme inhibitors. Reported incidence of dizziness is as low as 1% in patients with acute myocardial infarction to as high as 29% in patients with heart failure. Severe headaches and/or symptomatic hypotension may necessitate discontinuation of nitrate therapy. Severe life threatening hypotension or even death may occur when nitrates are used in patients with acute inferior myocardial infarction associated with right ventricular dysfunction or infarction, or with concomitant use of phosphodiesterase-5 inhibitors or N-acetylcysteine. Despite the disturbing observational reports in the literature that continuous and prolonged use of nitrates may lead to increased mortality and recurrent myocardial infarction in patients with stable coronary artery disease, no such adverse effects of nitrates have been reported in the large randomized trials in patients with acute myocardial infarction or chronic heart failure.
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PMID:Side effects of using nitrates to treat heart failure and the acute coronary syndromes, unstable angina and acute myocardial infarction. 1768 82

Cervicogenic headache (CEH) is a unilateral headache that can be provoked by neck movement, awkward head positions or pressure on tender points in the neck. The mechanisms underlying the stimulation of pain in CEH are not clearly known. In this study, we measured serum nitrate and nitrite levels as an index of nitric oxide (NO) activity in 15 patients with CEH during headache and headache-free periods and in 15 healthy controls. Total nitrate+nitrite levels were found to be higher in CEH patients during headache periods than in healthy controls (20.7+/-3.8 micromol/l vs 14.4+/-3.6 micromol/l, p<0.001), but not in CEH patients during headache-free periods (16.1+/-2.2 micromol/l) compared with the controls (p>0.05). In the patients with CEH, serum total nitrate+nitrite levels were found to be higher during headache periods than during headache-free periods (p=0.001). It can thus be hypothesized that the changes observed are a cause of the attack rather than a consequence of the disease process.
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PMID:Is there a role for nitric oxide activity in cervicogenic headache? 1792 65

(1) Anal fissures are very painful but often heal spontaneously. After eliminating other diagnoses, various treatments can be tried while waiting for fissures to heal: warm seat baths, local anaesthetics, and adequate fibre and fluid intake. (2) Clinical evaluation of glyceryl trinitrate 0.4% ointment, a nitrate derivative, is mainly based on a double-blind trial versus excipient in 193 adults with "chronic" fissures. This trial failed to show a clinically relevant analgesic effect of glyceryl trinitrate 0.4%, with only a 3-mm difference versus the excipient on a 100-mm pain rating scale. In another trial including 229 patients, neither 0.2% nor 0.4% glyceryl trinitrate was more effective on pain than placebo. (3) Another placebo-controlled trial including 304 adults treated for 8 weeks showed no efficacy of various doses of glyceryl trinitrate, versus the excipient, on the healing of anal fissures. (4) The most frequent adverse effect, as expected with a nitrate derivative, is headache, which affects about two-thirds of patients and is severe in 20% of cases. Abrupt-onset hypotension is a risk during concomitant use of other vasodilatory drugs. (5) There are no data on pregnant women exposed to glyceryl trinitrate. (6) In summary, glyceryl trinitrate 0.4% ointment does not reduce the pain linked to chronic anal fissures, but it does carry a risk of sometimes severe headache. It is best to continue using simple, non-aggressive treatments.
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PMID:0.4% glyceryl trinitrate ointment: new drug. Not useful for anal fissures. 1851 5

Long-term exposure to organic nitrates influences different sections of the vascular bed heterogeneously. Continuous dosage of nitrates leads to the development of tolerance both to the vascular effects and to the unwanted adverse effect, headache. Human data on the development of tolerance in different cranial arteries over more than 24 h are lacking. We compared the vascular changes of the middle cerebral, superficial temporal and radial arteries during oral administration of isosorbide-5-mononitrate (5-ISMN) 30 mg three times daily for 7 days in 11 healthy subjects in a double-blind, randomised, placebo controlled cross-over design. Blood velocity in the middle cerebral artery was measured with transcranial Doppler and the diameters of the temporal and radial arteries were measured with high frequency ultrasound. Headache recordings were compared to the observed vascular changes over time. Tolerance was complete within 24 h in the middle cerebral artery whilst in the superficial temporal and the radial arteries, tolerance was only partial and developed much more slowly, i.e. after 7 days correlating with the disappearance of NO-induced headache. The present study thus demonstrated the important differences in the time profiles of appearance of nitrate tolerance in arteries of different vascular beds in man. If vasodilatation is the cause of NO-induced headache the results point to extracerebral arteries as the locus of nociception. Due to a variety of other possible pain-inducing effects of nitric oxide our results do not exclude cerebral arteries.
J Headache Pain 2008 Aug
PMID:Nitric oxide-induced headache may arise from extracerebral arteries as judged from tolerance to isosorbide-5-mononitrate. 1852 38

Nitric oxide (NO), which modulates endothelial function, is thought to be pivotal in the pathophysiology of migraines. The connection between migraine and cardiovascular diseases has also drawn attention to the endothelial dysfunctions and NO pathway abnormalities seen in patients with migraine. Our goal was to assess the levels of NO and the endogenous NO synthase inhibitor, asymmetric dimethylarginine (ADMA), in people with migraine during the interictal period. A total of 49 patients with migraine and 22 control subjects were enrolled in the study. Their plasma NO metabolites (nitrite [NO2-] and nitrate [NO3-]) and ADMA levels were measured using the enzyme-linked immunosorbent assay method, and were then compared with their cardiovascular risk factors, anthropometric measurements, and headache frequency and severity. The plasma ADMA, NO2- and NO3- levels of the patients with migraine during the interictal period did not differ from the control group, and no relationship was found between cardiovascular risk factors and migraine attack severity and frequency. We conclude that, in patients with migraine, there is no dysfunction of baseline NO and ADMA metabolism during the interictal period.
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PMID:Asymmetric dimethylarginine and nitric oxide levels in migraine during the interictal period. 1928 79

Nitric oxide (NO) has been implicated in migraine attacks, but the role of NO in migraine remains unclear. We here hypothesize that increased NO in the headache-free period is associated with migraine. One hundred and thirty probands participated in this study. Various parameters of the NO pathway, such as nitrate, nitrite, arginine, citrulline, nitrosylated proteins, asymmetric dimethylarginine, symmetrical dimethylarginine, expression of endothelial nitric oxide synthase (eNOS) and inducible nitric oxide synthase and two polymorphisms of eNOS were investigated. We found significant increased nitrate and decreased nitrite levels in migraineurs in the headache-free period. Nitrate and nitrite levels showed a significant inverse correlation. Logistic regression revealed an odds ratio of 3.6 for migraine. Other parameters of the NO pathway were neither altered in migraineurs nor correlated with nitrate. We show here that migraine patients suffer under sustained increased nitrosative stress in the headache-free period, which is associated with a 3.6-fold higher risk for migraine.
Cephalalgia 2010 Apr
PMID:Increased nitric oxide stress is associated with migraine. 1967 97

Although nitrate therapy, used in the treatment of cardiovascular disorders, is frequently associated with side-effects, mainly headaches, the summaries of product characteristics of nitrate-containing medicines do not report detailed description of headaches and even do not highlight the possibility of nitrate-induced migraine. Two different types of nitrate-induced headaches have been described: (i) immediate headaches that develop within the first hour of the application, are mild or medium severity without characteristic symptoms for migraine, and ease spontaneously; and (ii) delayed, moderate or severe migraine-type headaches (occurring mainly in subjects with personal or family history of migraine), that develop 3-6 h after the intake of nitrates, with debilitating, long-lasting symptoms including nausea, vomiting, photo- and/or phono-phobia. These two types of headaches are remarkably different, not only in their timing and symptoms, but also in the persons who are at risk. Recent studies provide evidence that the two headache types are caused by different mechanisms: immediate headaches are connected to vasodilation caused by nitric oxide (NO) release, while migraines are triggered by other actions such as the release of calcitonin gene-related peptide or glutamate, or changes in ion channel function mediated by cyclic guanosine monophosphate or S-nitrosylation. Migraines usually need anti-attack medication, such as triptans, but these drugs are contraindicated in most medical conditions that are treated using nitrates. In conclusion, these data recommend the correction of summaries of nitrate product characteristics, and also suggest a need to develop new types of anti-migraine drugs, effective in migraine attacks, that could be used in patients with risk for angina pectoris.
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PMID:Headache-type adverse effects of NO donors: vasodilation and beyond. 2033 8

The pathophysiology of cluster headache (CH) is only partly understood. Nitric oxide (NO), a potent vasodilator, has been suggested to be involved, and increased plasma levels of nitrite, a stable product on NO degradation, have been identified in the active period and in remission. The aim of our study was to investigate the role of NO in CH by measuring its oxidation products, nitrite and nitrate, in the cerebrospinal fluid (CSF), a biological compartment closer to the supposed focus of the disorder. We collected CSF from 14 episodic CH patients. Lumbar puncture (LP) was performed at two occasions: in active period between headache attacks, and in remission, not earlier than three weeks after the last CH attack. Eleven healthy volunteers served as controls. To estimate NO production, we determined the levels of NO-oxidation end products (NOx), that is, the sum of nitrite and nitrate, by using capillary electrophoresis. CH patients in the active period had significantly increased NOx levels (mean 9.3, 95% confidence interval [CI] 8.5-10.1) compared with those in remission (mean 7.6, 95% CI 6.9-8.2; p < 001) and control subjects (mean 6.2, 95% CI 4.9-7.5; p < 0.001). CH patients also had statistically significant enhanced NOx levels in remission compared with those of control subjects (p = 0.034). CSF was also analysed with regard to inflammatory parameters and protein content. CSF showed signs of pleocytosis or oligoclonal bands or albumin increase in 43% of CH patients although these results were not conclusive. We suggest that CH patients have a generally raised NO tonus, both in the active period and in remission. We interpret these results as indications of a basal hyperfunction of the L-arginine-NO pathway, possibly as an expression of inflammatory activity, and sensitization of pain pathways. This is the first study analysing NOx in CSF in CH, and the results support NO involvement in the pathogenesis of CH.
Cephalalgia 2010 Jun
PMID:Levels of nitric oxide metabolites in cerebrospinal fluid in cluster headache. 2051 Dec 9


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