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

After thousands of painful long-lasting migraine or extremely violent cluster headache attacks no one has yet traced histological inflammatory or degenerative alterations of the interested tissues able to explain such dreadful pain. Therefore it has seemed logical to include these pains among the unjustified aimless, non finalized types of pain. Furthermore, clinical characteristics of automatism, explosiveness and the course of these pains resemble other aimless pains like those of organic deafferentation (phantom pain) which appear in a desensitized limb after denervation or even in amputated subjects. Intense and long lasting pains in opioid abstinence, mainly located in the chest and in the hip, also have all the characteristics of aimless pain. Idiopathic cephalic pain, together with deafferentation or opioid-abstinence pain, seems to be due to a dysafferentation which, through different channels, follows an analogous mechanism. This mechanism seems to be due to a deficit of autoanalgesia which in both organic deafferentation (phantom limb) and in opioid-abstinence can be related to the disuse of afferences' modulation. In idiopathic headache such a failure of autoanalgesia is likely to be due to a genetic, idiopathic mechanism. Headaches are characterized by a clear deficiency of autoanalgesia which may manifest itself not only at the level of the cephalic segment, which is so rich in afferences, but it may even involve the whole body. Even if pain is the compulsory phenomenon to diagnose headache, one must consider that migraine is a symptomatic triad in which vegetative and emotional phenomena also emerge. These phenomena are interindependent and not interdependent as each of them may appear as a first manifestation of an attack; one must therefore consider the possibility of a "unicum movens". Serotonin was taken into consideration because of its action which interests all or nearly all vegetative-emotional pain transmitting pathways. Today's identification of four types and various sub-types of 5-HT receptors has revealed the extraordinary eclecticism of this transmitter which within migraine's clinical expression underscores that migraine sufferers are characterized by a marked sensitivity to all the drugs capable of acutely or chronically interacting with serotonin metabolism and binding with many serotonin receptor types and sub-types. So even if the migraine sphinx still proposes its enigma, researchers--with their incurable curiosity--may not only find more and more accurate and effective medication for many human beings but also start penetrating a mystery, a great challenge to human imagination.
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PMID:[Noci-autonomic-affective automatism, the physiopathological essence of hemicrania. The serotonin theory as a guiding principle in the labyrinth of interpretations]. 129

After the synthetic serotonin 5-hydroxytryptamine (5-HT) became available in the early 1950s, attempts were soon under way to study the nature of 5-HT receptors. Using the guinea-pig isolated ileum, Gaddum and Picarelli (1957) suggested that 5-HT-induced contractions were mediated by a morphine-sensitive "M" receptor located on the parasympathetic ganglion and a dibenzyline-sensitive "D" receptor located on the smooth muscle. Though this classification ws used during the next three decades, it was realized that some effects of serotonin, for example vasoconstriction within the carotid vascular bed, were not mediated by either "M" or "D" receptors. When radioligand binding studies led to the identification of 5-HT1 and 5-HT2 "receptors" in the rat brain membranes, it became increasingly apparent that the two receptor classifications were not identical. Thus, a new framework for serotonin receptor nomenclature and classification was proposed: 5-HT1-like (5-HT1), 5-HT2 (formerly "D") and 5-HT3 (formerly "M") receptors. At the present time, several subtypes of 5-HT1 receptors as well as a 5-HT4 receptor are also recognized. As the serotonin receptor classification was emerging to indicate that carotid vasoconstriction by serotonin is mediated by a subtype of 5-HT1 receptors, on the migraine front it was being suggested that the disease is associated with vasodilation within the cranial extracerebral circulation and deranged serotonin metabolism and that certain antimigraine drugs caused a selective carotid vasoconstriction, probably via serotonin receptors. Therefore, Humphrey and colleagues conceived that synthesis of serotonin derivatives may lead to a compound that would elicit highly selective carotid vasoconstriction and abort migraine attacks. Indeed, via the synthesis of 5-carboxamidotryptamine and AH25086, sumatriptan was designed. The drug acts as an agonist at the vasoconstrictor 5-HT1 receptor subtype and has proved highly effective in the therapy of migraine attacks.
Cephalalgia 1992 Aug
PMID:From serotonin receptor classification to the antimigraine drug sumatriptan. 132

Headache, specifically migraine, is an extremely frequent and debilitating syndrome with worldwide prevalence, including indigenous cultures of Amazonia. This paper considers headache as perceived within the medical philosophy of 5 Indian tribes of the Ecuadorian Amazon Basin. Their ethnobotanical treatments for headache are examined, along with the limited available biochemical assay data. This information is analyzed by means of an Ethnopharmacology Rating Scale. Suggestions are offered as to methods of biochemical analysis that may be fruitful in assessment of potential clinical headache remedies. Key among these is the screening of ethnobotanical samples for serotonin receptor activity. The potential may exist for the discovery of more effective, less toxic headache drugs, as well as for the development of a new industry for the local economy that could promote conservation of an endangered ecosystem.
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PMID:Headache treatments by native peoples of the Ecuadorian Amazon: a preliminary cross-disciplinary assessment. 143 77

Recent evidence suggests that migraine may not be due to vasoconstriction followed by reactive vasodilation, and tension-type headache may not be due to excess muscle contraction. The prodromes of migraine may have a hypothalamic origin, and the aura and changes in cognition may have a cortical neuronal origin. The pain of migraine and tension-type headache may be generated centrally or enhanced or generated by neurogenic inflammation. Drugs used to treat headache frequently interact with serotonin receptor subtypes: abortive drugs at the 5-HT1 receptor and preventive drugs at the 5-HT2 receptor.
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PMID:Advances in understanding the pathophysiology of headache. 155 93

Ondansetron represents a new class of drugs that exert their antiemetic activity by selective inhibition of a serotonin receptor subtype (5-HT3). Ondansetron has marked activity against emesis associated with cisplatin and other highly emetogenic drugs. Compared with high doses of metoclopramide, the antiemetic "gold standard," it demonstrates equal or superior efficacy. Although ondansetron is moderately well absorbed after oral administration, only a parenteral formulation will initially be available. Ondansetron is eliminated almost entirely by hepatic metabolism; less than five percent of an intravenously administered dose is recovered intact in urine. The half-life of ondansetron is approximately 3.5 hours; slightly shorter in children and prolonged in the elderly. Neither clinical efficacy nor adverse effects have correlated with serum concentrations. Ondansetron is generally well tolerated. Clinically relevant adverse effects include headache, diarrhea or constipation, sedation, and transient minor elevations of liver function tests. It is not associated with extrapyramidal reactions. Ondansetron is indicated as prophylaxis for nausea and vomiting associated with emetogenic chemotherapy. Studies to further evaluate and define its use are ongoing.
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PMID:Ondansetron: a serotonin receptor (5-HT3) antagonist for antineoplastic chemotherapy-induced nausea and vomiting. 183 88

The antihypertensive efficacy of acute treatment with the serotonin receptor antagonist, ketanserin, in women with preeclampsia has been recently documented. The purpose of this study was to determine the safety and efficacy of chronic ketanserin treatment in a group of 20 hypertensive pregnant women: 10 received daily oral doses of ketanserin (20-80 mg), and 10 were treated with oral alpha-methyldopa (500-2000 mg). This study includes (a) patients with a sustained elevation of systolic blood pressure higher than 159 mm Hg and/or diastolic blood pressure higher than 99 mm Hg at bed rest, and (b) hypertensive patients with systolic blood pressure higher than 140 mm Hg or diastolic blood pressure higher than 90 mm Hg with superimposed symptoms such as headaches, stomach aches, and neurological disturbances. A significant and comparable decrease in blood pressure was noted in both groups, in relation with pretreatment levels; no adverse affects were observed in mother or fetus from the ketanserin and alpha-methyldopa groups.
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PMID:Ketanserin versus alpha-methyldopa in the treatment of hypertension during pregnancy: a preliminary report. 244 54

The endocrinological actions of quipazine, a direct serotonin receptor agonist, were investigated in both normal subjects (NS) and individuals with neurological disorders, i.e., Huntington's disease (HD), myoclonic epilepsy (ME) and cluster headache (CH). In both normal subjects and neurologic patients inconsistent and variable changes in the secretion of anterior pituitary hormones were observed. In fact, oral administration of 50 mg of quipazine elicited a rise in plasma GH in only 9/23 subjects investigated (3 NS, 2 HD, 1 ME, 3 CH), decreased GH in 4 subjects (1 NS, 2 HD, 1 CH) and left unmodified plasma GH in the remaining 10 subjects. Only 7/23 subjects showed a positive PRL response to quipazine (2 NS, 1 HD, 1 ME, 3 CH), in one subject (CH) PRL was inhibited while the drug was ineffective in the remaining 15 subjects. For gonadotropins, 5/21 subjects (2 NS, 1 HD, 2 CH) had a positive LH response and 3/20 subjects (1 NS, 1 ME, 1 CH) had a positive FSH response. In one subject (HD) there was inhibition of baseline LH levels and no effects were present in the remaining individuals. No changes in basal TSH levels were present in the 6 subjects investigated (4 NS, 2 ME). Quipazine was instead competent to increase plasma cortisol levels in 6/8 normal subjects. Pharmacodynamic, mainly gastrointestinal, effects of the drug were present in about 50% of the subjects but were not or only poorly correlated with the endocrine responses. Collectively, based on the neuropharmacologic profile of the drug, and in contrast to many animal data, these findings do not support a major role for the serotoninergic system on basal anterior pituitary hormone secretion in man, possibly with the exception of the ACTH-cortisol secretion.
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PMID:Neuroendocrine effects of quipazine in man in health state or with neurological disorders. 644 95

This is the first double-blind clinical trial in a homogenous group of patients to compare the recommended dosing schedules of ondansetron and granisetron in the control of prolonged emesis after cyclophosphamide-containing chemotherapy (48% CMF, 35% EC) for breast cancer. A total of 514 patients were recruited. Of the 488 patients included in the intent-to-treat analyses, 167 were randomised to group A [8 mg ondansetron intravenously (i.v.) + placebo by mouth (p.o.) before chemotherapy + 8 mg ondansetron p.o. twice daily (b.d.) until day 5], 155 to group B (placebo i,.v. + 8 mg ondansetron p.o. before chemotherapy + 8 mg ondansetron p.o. b.d. until day 5) and 166 to group C (3 mg granisetron i.v. + placebo p.o. before chemotherapy + placebo p.o. b.d. until day 5). On study day 1, the groups were comparable with respect to the proportion of patients experiencing up to 2 emetic episodes (group A: 89%; B: 86%; C: 91%) and in the severity of nausea (no nausea; group A: 51%; B: 55%; C: 54%). Over the 5-day study period significantly more patients were rescued or withdrawn due to lack of response after the granisetron regimen (26%) than after the i.v. + p.o. ondansetron regimen (11%; p < 0.001). Since there was no difference in these parameters on day 1, this reflects differences on days 2-5 and was also reflected in the all-oral ondansetron group over this period (group B: 12%; C: 22% on days 2-5). A significant difference in the severity of nausea after i.v. and p.o. ondansetron compared with granisetron was also observed over the 5-day study period (p = 0.009). This was reflected in a numerical difference in favour of the all-p.o. ondansetron regimen compared with the granisetron regimen (no nausea; group A: 33%; B: 34%; C: 25%). Again these differences reflected differences in nausea control on days 2-5, since no differences were observed on day 1. Logistic regression analyses adjusted for prognostic factors also revealed a significant difference (p = 0.011) in favour of the i.v. + ondansetron group compared with the granisetron group when complete plus major response was compared over days 2-5. No significant differences in the safety profiles of the three treatment groups were observed. There were no severe or unexpected drug-related adverse events and as is well established for the serotonin receptor antagonists, mild constipation (mean 8%) and mild headache (mean 8%) were most commonly reported.
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PMID:Ondansetron compared with granisetron in the prophylaxis of cyclophosphamide-induced emesis in out-patients: a multicentre, double-blind, double-dummy, randomised, parallel-group study. Emesis Study Group for Ondansetron and Granisetron in Breast Cancer Patients. 771 4

Headaches belong to the most frequent sufferings. According to certain most modern epidemiological studies about 20% of adults have recurrent headaches, among them particularly migraine and tension headache. In recent years the interest in these conditions had increased resulting in a great number of research works. A great role is played by the International Headache Society, and the newly formed European Federation of Headaches. In 1988 a universally accepted classification, and diagnostic criterias were elaborated and have been accepted by the Polish neurologists. Tens or research centres are studying the problems in this field. The main directions of studies are-the role of neurotransmitters, the vascular system of the head, the mechanisms of autonomic regulation, the role of neurogenic bland inflammation in the generation of pain, and the psycho-emotional factors. A number of new clinical forms of headache have been described. Therapeutic possibilities have also increased (beta-blockers, calcium blockers, serotonin receptor drugs, eg. sumatriptan, microsurgery of neuralgias etc). This opens a new period for satisfactory advances in that rather marginal, as yet, area.
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PMID:[Present problems of migraine and similar headaches]. 791 20

Dolasetron mesylate (MDL 73,147EF), a new serotonin receptor (5-HT3) antagonist was administered to 164 cancer patients naive or non-naive to chemotherapy, in single, rising doses of 10, 20, 30, 40, or 50 mg i.v. 15 minutes prior to an infusion of cisplatin. The severity of nausea and number of episodes of emesis were recorded during the 24-hour period following cisplatin administration. There were significant differences between the dose groups, sex, and naive and non-naive patients. There were also significant dolasetron dose-dependent differences for no emesis (p = .01), less than 3 emetic episodes (p = .01), time-to-onset of nausea (p = .04), and time-to-onset of emesis (p = .003). The severity of symptoms was greater for females, for patients with previous chemotherapy, and with shorter duration of cisplatin infusion. Adjustment for these variables and the study center reduced the associations between the dose of dolasetron mesylate and the outcome variables. The principal adverse events were headache (11%) and diarrhea (6%). Dolasetron mesylate was well tolerated; a single dose of 40 or 50 mg controlled acute nausea and vomiting induced by highly emetogenic chemotherapy in the majority, in particular in chemotherapy-naive and male patients. In conclusion, 50 mg and a larger dose merit study in controlled trials with stratification for sex and previous chemotherapy.
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PMID:Acute antiemetic efficacy and safety of dolasetron mesylate, a 5-HT3 antagonist, in cancer patients treated with cisplatin. European Dolasetron Study Group. 814 Nov 14


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