Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0030193 (pain)
 261,466 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

(+/-)3,4-Methylenedioxymethamphetamine (MDMA; "Ecstasy"), an increasingly popular recreational drug, is known to damage brain serotonin 5-hydroxytryptamine (5-HT) neurons in experimental animals. Whether MDMA is neurotoxic in humans has not been established. Thirty MDMA users and 28 controls were admitted to a controlled inpatient setting for measurement of biologic and behavioral indexes of central 5-HT function. Outcome measures obtained after at least 2 weeks of drug abstinence included concentrations of monoamine metabolites in cerebrospinal fluid (CSF), prolactin responses to L-tryptophan, nociceptive responses to ischemic pain, and personality characteristics in which 5-HT has been implicated (i.e., impulsivity and aggression). Subjects with a history of MDMA exposure had lower levels of CSF 5-hydroxyindoleacetic acid (the major metabolite of 5-HT) than controls (p = .001). Although they resembled controls in their prolactin response to L-tryptophan and their response to ischemic pain, MDMA users had lower scores on personality measures of impulsivity (p = .004) and indirect hostility (p = .009). The CSF findings suggest that 5-HT neurotoxicity may be a potential complication of MDMA use. Further, differences in personality support the view that 5-HT systems are involved in modulating impulsive and aggressive personality traits. Additional studies of MDMA-exposed individuals are needed to confirm and extend the present findings. Such studies could help elucidate the role of 5-HT in normal brain function as well as in neuropsychiatric disease states.
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PMID:Serotonin neurotoxicity after (+/-)3,4-methylenedioxymethamphetamine (MDMA; "Ecstasy"): a controlled study in humans. 751 77

Since the first comprehensive description of the symptoms of FMS by Yunus et al (1981), numerous investigations have confirmed that FMS is a clinical entity. However, the aetiology of the syndrome is still not fully elucidated. It seems, however, logical to place the origin of the disorder in the muscle. Muscle pain, especially at the muscle-tendon junctions, fatigue and stiffness are the first symptoms. A malfunction of energy metabolism has been detected in part of the muscle fibres. However, it has to be considered that the muscle is not an isolated entity. Its activity is controlled by segmentally arranged motor units of the ventral horn of the spinal cord in response to proprioceptive afferent signals arising in the muscle spindles or in other sensory elements including nociceptors. Together with supraspinal descending inputs, the spinal motor neurone pool is the common final pathway for segmental and suprasegmental inputs, making the motor system extremely powerful for adaptive adjustments but also vulnerable if deficits occur in either of these input levels. A second, recently discovered abnormality seen in FMS is a lowered serotonin level in peripheral and most likely also central structures. The underlying mechanism seems to be defective absorption of the precursor amino acid tryptophan from the gut. Serotonin is involved centrally in the regulation of the sleep pattern, and at the spinal level it acts as a 'gain setter' of motoneurone excitability and suppresses signal transmission of noxious stimuli in dorsal horn neurones. Either of these two disturbances, muscle energy depletion or serotonin deficiency, could by itself evoke many of the symptoms of FMS, and their combined appearance will perpetuate the disease. Depressed levels of somatomedin C, caused by a deficit of stage 4 sleep-dependent release of GH, might represent an additional factor in preventing proper development or repair of myoskeletal structures. Malabsorption of certain amino acids, possibly due to a genetic disorder of gut transport mechanisms, may constitute an additional deleterious factor. The abnormalities found in the HPA and HPT axis may be seen as an attempt of the organism to restore homeostasis. The stimulus eliciting this counter-regulatory reaction may be pain or other afferent signals which normally do not reach the central nervous system. It is doubtful whether the unspecific activation of the HPA axis in a non-inflammatory disease is beneficial.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Neuromediator and hormonal perturbations in fibromyalgia syndrome: results of chronic stress? 785 Aug 79

Because circulating melatonin levels are generally thought to be under the strict control of pineal N-acetyltransferase, little attention has been paid to the impact of an altered availability of serotonin (5-HT) on melatonin formation. In order to see whether melatonin synthesis is stimulated by an increased availability of free, cytosolic 5-HT, we studied the effects of 5-HT precursors, 5-HT releasers and reuptake inhibitors and of monoamine oxidase inhibitors, alone and in combination, on circulating melatonin levels in experimental animals. The administration of tryptophan and 5-HT-releasing drugs (fenfluramine, +/- 3,4-methylenedioxymethamphetamine) to rats caused a dose- and time-dependent elevation of circulating melatonin levels during the day and night. This increase in melatonin was further enhanced by inhibition of monoamine oxidase. The elevation of plasma melatonin caused by 5-HT-releasing drugs was prevented by prior administration of fluoxetine. Monoamine oxidase inhibitors and fluoxetine alone had no effect on circulating melatonin levels. These findings indicate that the administration of indirectly acting 5-HT receptor agonists which increase the free cytoplasmic pool of 5-HT may also elevate circulating melatonin levels. The results of this study suggest that the rate of pineal melatonin synthesis is dependent on the free cytoplasmic pool of 5-HT in pinealocytes and that the drug-induced elevation of this pool stimulates melatonin formation and increases circulating melatonin levels. At least some of the effects of indirectly acting 5-HT receptor agonists, e.g. on sleep, mood, food intake, pain perception, and neuroendocrine secretion, may therefore be mediated by the elevation of circulating melatonin and the subsequent activation of central melatonin receptors.
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PMID:Effects of indirectly acting 5-HT receptor agonists on circulating melatonin levels in rats. 840 95

Serotonin-releasing brain neurons are unique in that the amount of neurotransmitter they release is normally controlled by food intake: Carbohydrate consumption--acting via insulin secretion and the "plasma tryptophan ratio"--increases serotonin release; protein intake lacks this effect. This ability of neurons to couple neuronal signaling properties to food consumption is a link in the feedback mechanism that normally keeps carbohydrate and protein intakes more or less constant. However, serotonin release is also involved in such functions as sleep onset, pain sensitivity, blood pressure regulation, and control of the mood. Hence many patients learn to overeat carbohydrates (particularly snack foods, like potato chips or pastries, which are rich in carbohydrates and fats) to make themselves feel better. This tendency to use certain foods as though they were drugs is a frequent cause of weight gain, and can also be seen in patients who become fat when exposed to stress, or in women with premenstrual syndrome, or in patients with "winter depression," or in people who are attempting to give up smoking. (Nicotine, like dietary carbohydrates, increases brain serotonin secretion; nicotine withdrawal has the opposite effect.) It also occurs in patients with normal-weight bulimia. Dexfenfluramine constitutes a highly effective treatment for such patients. In addition to producing its general satiety-promoting effect, it specifically reduces their overconsumption of carbohydrate-rich (or carbohydrate-and fat-rich) foods.
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PMID:Brain serotonin, carbohydrate-craving, obesity and depression. 869 46

The results of stimulating human subjects with the LISS Cranial Stimulator (LCS) and the LISS Body Stimulator (LBS) include an increase or decrease in the activities of certain neurotransmitters and neurohormones and the reduction of associated pain, insomnia, depression, and spasticity. The effects were documented in human subjects with measurements of the serum concentration of the various agents and assessments of the symptoms being performed before and after stimulation. The stimulators had a carrier frequency of 15,000 hz, which utilizes the bulk capacitance of the body, and a 15 hz modulating bioactive frequency. The second modulating frequency presently used, 500 hz, reduces the energy input to the patient by half. Significant increases in levels of CSF serotonin and beta endorphin were recorded post stimulation. There were also elevations in the levels of plasma serotonin, beta endorphin, GABA and DHEA together with diminished levels of cortisol and tryptophan. Concomitant with these changes were significant improvements in the symptoms of pain, insomnia, spasticity, depression, and headache.
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PMID:Physiological and therapeutic effects of high frequency electrical pulses. 880 93

The neurotransmitter serotonin plays a modulatory role in the regulation of various cognitive and behavioral functions such as sleep, mood, pain, depression, anxiety, and learning by binding to a number of serotonin receptors present upon the cell surface. The spectroscopic properties of serotonin and their modulation with ionization state have been studied. Results show that serotonin fluorescence, as measured by its intensity, emission maximum, and lifetime, is pH dependent. These results are further supported by absorbance changes that show very similar pH dependence. Changes in fluorescence intensity and absorbance as a function of pH are consistent with a pK(a) of 10.4 +/- 0.2. The ligand-binding site for serotonin receptors is believed to be located in one of the transmembrane domains of the receptors. To develop a basis for monitoring the binding of serotonin to its receptors, its fluorescence in nonpolar media has been studied. No significant binding or partitioning of serotonin to membranes under physiological conditions was observed. Serotonin fluorescence in solvents of lower polarity is characterized by an enhancement in intensity and a blue shift in emission maximum, although the solvatochromism is much less pronounced than in tryptophan. In view of the multiple roles played by the serotonergic systems in the central and peripheral nervous systems, these results are relevant to future studies of serotonin and its binding to its receptors.
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PMID:Photophysics of a neurotransmitter: ionization and spectroscopic properties of serotonin. 888 69

Although fish venoms exert a cardiovascular effect, the presence of adrenergic substances was not previously demonstrated. Chromatographic analysis with electrochemical detection showed the presence of substances co-migrating with norepinephrine, dopamine and tryptophan. Serotonin, which was thought to be implicated in the intense pain following fish envenomation, was not detected. Norepinephrine was identified as a component of the stonefish Synanceia verrucosa venom by gas chromatography-mass spectrometry.
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PMID:Presence of norepinephrine and other biogenic amines in stonefish venom. 895 81

The administration of carbamazepine to rats caused a significant increase in pain threshold values. Furthermore, treatment with carbamazepine lowered the concentration of tryptophan bound to plasma proteins and elevated the brain serotonin values. The high brain serotonin levels, observed in carbamazepine-treated rats, are probably attributable to an increased availability of brain tryptophan, since this amino acid has been substantially removed from the plasma protein compartment by carbamazepine treatment, which exhibits a high binding capacity to plasma proteins. The analgesic effects caused by carbamazepine administration have been attributed to increased levels of brain serotonin which is involved in the control of pain transmission.
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PMID:Effects of carbamazepine treatment on pain threshold values and brain serotonin levels in rats. 912 33

Recently, a novel cholinergic channel modulator, (R)-5-(2-azetidinylmethoxy)-2-chloropyridine (ABT-594), was shown to produce potent analgesia in a variety of rodent pain models when administered either systemically or centrally into the nucleus raphe magnus (NRM). The purpose of the present study was to investigate the possible supraspinal contribution of ABT-594 by assessing its ability to induce expression of the immediate early gene c-fos, a biochemical marker of neuronal activation, in the NRM of rats. Putative serotonergic neurons in the NRM, a medullary nucleus proposed to be involved in descending antinociceptive pathways, were identified immunohistochemically using a monoclonal antibody (mAb) against tryptophan hydroxylase. ABT-594 (0.03-0.3 micromol/kg, i.p.) produced a dose-dependent induction of Fos protein that was blocked by the central nicotinic acetylcholine receptor (nAChR) antagonist mecamylamine (5 micromol/kg, i.p.) but not by the peripheral nAChR antagonist hexamethonium (15 micromol/kg, i.p.). Immunohistological studies using mAb 299 revealed the expression of alpha4-containing nAChRs in the NRM. The alpha4 immunostaining was dramatically reduced by pretreating (30 d) animals with the serotonin neurotoxin 5,7-dihydroxytryptamine (5,7-DHT), which was previously shown to substantially attenuate the antinociceptive actions of ABT-594. In a double immunohistochemical labeling experiment, coexpression of the serotonin marker tryptophan hxdroxylase and the alpha4 nAChR subunit in NRM neurons was observed. These results suggest that the analgesic mechanism of ABT-594 may in part involve the activation of the NRM, a site where alpha4-containing nAChRs are expressed by serotonergic neurons.
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PMID:Role of the nucleus raphe magnus in antinociception produced by ABT-594: immediate early gene responses possibly linked to neuronal nicotinic acetylcholine receptors on serotonergic neurons. 965 Dec 24

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


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