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

Cultural, psychological, and biochemical explanations for depression in users of oral contraceptives are discussed. The suppression of taboos against sexuality cannot be expected to bring about instant psychological adjustment, as shown by the large numbers of women who are afraid to take the pill or who develop psychosomatic disorders and depression. Incidence of depression as reported in the literature ranges from 5% to 45%. Some authors attribute psychogenic causes for depression associated with the pill, such as temporary castration, instant sexual liberation, or womens' undeniable maternal instinct. Others present evidence for biochemical causes of depression. General explanations for pill-related depression include imbalance of hypothalamic amines and consequently of releasing factor, prolactin-inhibiting factor, decreased brain serotonin due to inhibition of tryptophan hydroxylase by progestagens, or diminished brain biogenic amines because of lowered pyridoxal levels. From clinical work with neuroleptic drugs it is known that drugs, stress, or anxiety can disturb the biochemical balance and result in amenorrhea. High progestin levels may be responsible for premenstrual anxiety and headaches.
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PMID:[Oral contraception and induced depressive states]. 444 85

Cerebral tryptophan metabolism was studied in rat brain slices. The results show that serotonin production was inhibited at high levels of tryptophan or 5-oxo-L-prolyltryptophan. In contrast, kynurenine formation showed a dose dependent increase at the various concentrations of tryptophan or 5-oxo-L-prolyltryptophan. Measurements of the activities of tryptophan hydroxylase (TH) and indoleamine 2,3-dioxygenase (IDOase) in crude brain homogenates showed that serotonin formation was linear in the presence of dithiothreitol, whereas kynurenine production was inhibited in the presence of dithiothreitol or superoxide dismutase. These results suggest an inverse relationship in the regulation of 5-hydroxyindole and kynurenine pathways. The former being inhibited in the presence of high tryptophan concentration while the latter is enhanced. Furthermore, a high intracellular thiol-disulphide ratio appears to favour serotonin formation, whereas a highly reducing environment decreases kynurenine production.
Cephalalgia 1983 Aug
PMID:Regulation of cerebral kynurenine and 5-hydroxyindole pathways during tryptophan loading. 660 81

5-Hydroxytryptophan (5-HTP) is the intermediate metabolite of the essential amino acid L-tryptophan (LT) in the biosynthesis of serotonin. Intestinal absorption of 5-HTP does not require the presence of a transport molecule, and is not affected by the presence of other amino acids; therefore it may be taken with meals without reducing its effectiveness. Unlike LT, 5-HTP cannot be shunted into niacin or protein production. Therapeutic use of 5-HTP bypasses the conversion of LT into 5-HTP by the enzyme tryptophan hydroxylase, which is the rate-limiting step in the synthesis of serotonin. 5-HTP is well absorbed from an oral dose, with about 70 percent ending up in the bloodstream. It easily crosses the blood-brain barrier and effectively increases central nervous system (CNS) synthesis of serotonin. In the CNS, serotonin levels have been implicated in the regulation of sleep, depression, anxiety, aggression, appetite, temperature, sexual behaviour, and pain sensation. Therapeutic administration of 5-HTP has been shown to be effective in treating a wide variety of conditions, including depression, fibromyalgia, binge eating associated with obesity, chronic headaches, and insomnia.
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PMID:5-Hydroxytryptophan: a clinically-effective serotonin precursor. 972 88

Migraine is a common debilitating primary headache disorder with significant mental, physical and social health implications. The brain neurotransmitter 5-hydroxytryptamine (5-HT; serotonin) is involved in nociceptive pathways and has been implicated in the pathophysiology of migraine. With few genetic studies investigating biosynthetic and metabolic enzymes governing the rate of 5-HT activity and their relationship to migraine, it was the objective of this study to assess genetic variants within the human tryptophan hydroxylase (TPH), amino acid decarboxylase (AADC) and monoamine oxidase A (MAOA) genes in migraine susceptibility. This objective was undertaken using a high-throughput DNA pooling experimental design, which proved to be a very accurate, sensitive and specific method of estimating allele frequencies for single nucleotide polymorphism, insertion deletion and variable number tandem repeat loci. Application of DNA pooling to a wide array of genetic loci provides greater scope in the assessment of population-based genetic association study designs. Despite the application of this high-throughput genotyping method, negative results from the two-stage DNA pooling design used to screen loci within the TPH, AADC and MAOA genes did not support their role in migraine susceptibility.
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PMID:A genetic analysis of serotonergic biosynthetic and metabolic enzymes in migraine using a DNA pooling approach. 1620 Mar 90

Migraine is a chronic episodic disorder that has been linked to abnormalities in serotonin signaling and abnormal function of a presynaptic voltage-gated calcium channel, CACNA1A. Although the importance of serotonin to migraine tendency suggests a link between serotonergic signaling and CACNA1A function, the nature of this connection remains unclear in vertebrate studies. This article reviews findings, based on an invertebrate model of CACNA1A dysfunction, which suggest a potential connection between serotonergic and calcium channel abnormalities in migraine. Neurons of the invertebrate species Caenorhabditis elegans express a voltage-gated calcium channel, UNC-2, which is the closest ortholog in C. elegans of human CACNA1A. Mutations in unc-2, the gene that encodes this invertebrate channel, cause the animals to be lethargic and uncoordinated. By identifying the genes that could be altered in such a way as to suppress the lethargic phenotype of unc-2, a signaling pathway has been identified through which UNC-2 calcium channel function antagonizes a transforming growth factor-beta (TGF-beta) pathway modulating locomotion. In C. elegans, serotonergic signaling can inhibit the rate of movement. The UNC-2/transforming growth factor-beta pathway identified regulates the expression of a gene encoding the rate-limiting enzyme for serotonin synthesis, tryptophan hydroxylase. The evolutionary and functional relationship between the UNC-2 channel and the migraine-associated CACNA1A channel was further confirmed through experiments showing that transgenic expression of human CACNA1A can suppress the lethargic and serotonin-deficient phenotypes of unc-2 mutant animals. The findings in this invertebrate model constitute the first direct demonstration of how CACNA1A function might affect the levels of serotonin, a neurotransmitter known to be important in migraine.
Headache 2006 Jun
PMID:Invertebrate modeling of a migraine channelopathy. 1692 61

A number of pain conditions, acute as well as chronic, are much more prevalent in women, such as temporomandibular disorder (TMD), irritable bowel syndrome, fibromyalgia, and migraine. The association of female sex steroids with these nociceptive conditions is well known, but the mechanisms of their effects on pain signaling are yet to be deciphered. We reviewed the mechanisms through which female sex steroids might influence the trigeminal nociceptive pathways with a focus on migraine. Sex steroid receptors are located in trigeminal circuits, providing the molecular substrate for direct effects. In addition to classical genomic effects, sex steroids exert rapid nongenomic actions to modulate nociceptive signaling. Although there are only a handful of studies that have directly addressed the effect of sex hormones in animal models of migraine, the putative mechanisms can be extrapolated from observations in animal models of other trigeminal pain disorders, like TMD. Sex hormones may regulate sensitization of trigeminal neurons by modulating expression of nociceptive mediator such as calcitonin gene-related peptide. Its expression is mostly positively regulated by estrogen, although a few studies also report an inverse relationship. Serotonin (5-Hydroxytryptamine [5-HT]) is a neurotransmitter implicated in migraine; its synthesis is enhanced in most parts of brain by estrogen, which increases expression of the rate-limiting enzyme tryptophan hydroxylase and decreases expression of the serotonin re-uptake transporter. Downstream signaling, including extracellular signal-regulated kinase activation, calcium-dependent mechanisms, and cAMP response element-binding activation, are thought to be the major signaling events affected by sex hormones. These findings need to be confirmed in migraine-specific animal models that may also provide clues to additional ion channels, neuropeptides, and intracellular signaling cascades that contribute to the increased prevalence of migraine in women.
Headache 2011 Jun
PMID:Mechanisms of pain modulation by sex hormones in migraine. 2163 76

Ecstasy is a widely used recreational drug that usually consists primarily of 3,4-methylenedioxymethamphetamine (MDMA). Most ecstasy users consume other substances as well, which complicates the interpretation of research in this field. The positively rated effects of MDMA consumption include euphoria, arousal, enhanced mood, increased sociability, and heightened perceptions; some common adverse reactions are nausea, headache, tachycardia, bruxism, and trismus. Lowering of mood is an aftereffect that is sometimes reported from 2 to 5 days after a session of ecstasy use. The acute effects of MDMA in ecstasy users have been attributed primarily to increased release and inhibited reuptake of serotonin (5-HT) and norepinephrine, along with possible release of the neuropeptide oxytocin. Repeated or high-dose MDMA/ecstasy use has been associated with tolerance, depressive symptomatology, and persisting cognitive deficits, particularly in memory tests. Animal studies have demonstrated that high doses of MDMA can lead to long-term decreases in forebrain 5-HT concentrations, tryptophan hydroxylase activity, serotonin transporter (SERT) expression, and visualization of axons immunoreactive for 5-HT or SERT. These neurotoxic effects may reflect either a drug-induced degeneration of serotonergic fibers or a long-lasting downregulation in 5-HT and SERT biosynthesis. Possible neurotoxicity in heavy ecstasy users has been revealed by neuroimaging studies showing reduced SERT binding and increased 5-HT2A receptor binding in several cortical and/or subcortical areas. MDMA overdose or use with certain other drugs can also cause severe morbidity and even death. Repeated use of MDMA may lead to dose escalation and the development of dependence, although such dependence is usually not as profound as is seen with many other drugs of abuse. MDMA/ecstasy-dependent patients are treated with standard addiction programs, since there are no specific programs for this substance and no proven medications. Finally, even though MDMA is listed as a Schedule I compound by the Drug Enforcement Agency, MDMA-assisted psychotherapy for patients with chronic, treatment-resistant posttraumatic stress disorder is currently under investigation. Initial results show efficacy for this treatment approach, although considerably more research must be performed to confirm such efficacy and to ensure that the benefits of MDMA-assisted therapy outweigh the risks to the patients.
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PMID:3,4-methylenedioxymethamphetamine (MDMA): current perspectives. 2464 91