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Query: UMLS:C0030193 (pain)
 261,466 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The synthesis of neurotransmitters in mammalian brain responds rapidly to changes in precursor availability. Serotonin synthesis depends largely on the brain concentrations of L-tryptophan, its precursor amino aicd. This relationship appears to be physiologic: when brain tryptophan levels vary because of insulin secretion or meal ingestion, corresponding alterations occur in the rate of serotonin formation. The ability of any food to modify brain tryptophan (and serotonin) depends on how its ingestion changes the serum concentration of not only tryptophan, but also several other large neutral amino acids that compete with tryptophan for uptake into the brain. Such precursor-induced changes in brain serotonin appear to be functionally important: animals having a reduced level of brain serotonin (caused by the chronic ingestion of a naturally tryptophan-poor diet, such as corn) demonstrate a heightened sensitivity to painful stimuli; this pain sensitivity can be acutely restored to normal values by a single injection of L-tryptophan, which rapidly elevates brain serotonin. The synthesis of catecholamines (e.g., dopamine, norepinephrine) in the brain also varies with the availability of the precursor amino acid L-tyrosine. Single injections of this amino acid increase brain tyrosine levels and accelerate brain catechol synthesis, while injections of a competing neutral amino acid (e.g., leucine, tryptophan) reduce brain tyrosine and its rate of conversion to dopa. The rate of catecholamine synthesis, however, appears to be influenced less by precursor levels than is serotonin formation: tyrosine hydroxylase, whcih catalyzes the rate-limiting step in catecholamine synthesis, responds strongly to end-product inhibition and to other controls that reflect variations in neuronal activity. The synthesis of acetylcholine in brain responds to substrate (choline) availability much like serotonin synthesis. Short-term alterations in brain choline levels are mirrored by similar changes in brain acetylcholine concentration. Variations in the daily dietary intake of choline also modify brain choline and acetylcholine. The relationship between choline availability and acetylchyoline synthesis has already foudn a cletween choline availability and acetylchyoline synthesis has already found a clinical application: choline has been used successfully in the treatment of tardive dyskinesia, a disorder of the central nervous system thought to reflect a deficiency in cholinergic transmission. These relationships between precursor availability from the periphery and brain neurotransmitter synthesis may ultimately provide the brain with information about peripheral metabolic state.
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PMID:Effects on the diet on brain neurotransmitters. 1 61

Both the learning of brightness discrimination, discrimination reversal and a simple oddity problem, and the pain-sensitivity to electric shock were studied in rats treated with 100 mg/kg of D, L-parachlorophenylalanine (PCPA), 100 mg/kg of D, L-tryptophan (TP) or 2.0 ml/kg of control solution (CS). At the end of the last behavioral session all animals were killed and the levels and rate of 5-hydroxytryptamine (5-HT) synthesis were measured. PCPA treatments produce rats which are more effective in coping with a problem; these animals were similar in that both the levels and turnover rate of brain 5-HT and the pain-sensitivity were lower. Results are tentatively explained suggesting that these differences in learning ability could be a result of the drug's action in pain-sensitivity. The possibility that 5-HT might be responsible for these differences is discussed.
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PMID:Effects of para-chlorophenylalanine and tryptophan on learning of a brightness discrimination in rats. 13 33

Monoamines are involved in the central nervous assimilation and modulation of the pain flow. According to a personal hypothesis, a disorder of this biochemical control (in particular a precariousness of brain 5-hydroxytryptamine turnover), is the basic mechanism of some painful conditions, such as migraine and other essential headaches. Acute (infusion) and chronic (ingestion) administration of tryptophan to migraine-headache sufferers improved the clinical course significantly in respect to placebo. Few patients with untractable pain from disseminated cancer received daily infusion of tryptophan and ingested a few gr of this amnioacid: improvement of pain and reduction of morphine necessity was observed. Parachlorophenylalanine chronic administration in migraine-headache sufferers lowered the pain threshold so far as to provoke (in 20% of cases) spontaneous pains in the trunk, legs and arms. This systemic pain syndrome was promptly reversible by discontinuing the treatment. Spontaneous pain syndrome was not reported by others in the healthy subject; this suggests an apparent vulnerability of 5HT turnover in essential headaches.
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PMID:5-Hydroxytryptamine and pain modulation in man: a clinical pharmacological approach with tryptophan and parachlorophenylalanine. 14 17

In this study the role of serotonin in pain sensitivity was investigated. Brain serotonin was elevated via low and high doses of precursor tryptophan and lowered via parachlorophenylalanine or lesions placed in the dorsal raphe nucleus. The effects on pain sensitivity were then assessed using two psychophysical pain testing procedures: (1) minimum shock intensity (threshold) which produced a conditioned escape response; and (2) total activity elicited by highly aversive inescapable shock. The results showed that only a large elevation of serotonin produced a change in escape thresholds in the direction of hypoalgesia. When total activity to a painful inescapable stimulus was evaluated only lowering of serotonin produced an effect, and this change was in the direction of hyperalgesia. The conclusion was made that serotonin does contribute to the mechanism of pain.
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PMID:Effects of serotonin content on pain sensitivity in the rat. 15 65

Plasma-free tryptophan is inversely related to the severity of subjective pain in 8 patients who fulfilled criteria for a variety of non-articular rheumatism, the "fibrositis syndrome". The observation is consistent with animal and human studies suggesting a relationship between reduced brain serotonin metabolism and pain reactivity.
Pain 1978 Jun
PMID:Plasma tryptophan and musculoskeletal pain in non-articular rheumatism ("fibrositis syndrome"). 30 24

Animal data indicate that serotonin (5-HT) is a major neurotransmitter involved in the control of numerous central nervous system functions including mood, aggression, pain, anxiety, sleep, memory, eating behavior, addictive behavior, temperature control, endocrine regulation, and motor behavior. Moreover, there is evidence that abnormalities of 5-HT functions are related to the pathophysiology of diverse neurological conditions including Parkinson's disease, tardive dyskinesia, akathisia, dystonia, Huntington's disease, familial tremor, restless legs syndrome, myoclonus, Gilles de la Tourette's syndrome, multiple sclerosis, sleep disorders, and dementia. The psychiatric disorders of schizophrenia, mania, depression, aggressive and self-injurious behavior, obsessive compulsive disorder, seasonal affective disorder, substance abuse, hypersexuality, anxiety disorders, bulimia, childhood hyperactivity, and behavioral disorders in geriatric patients have been linked to impaired central 5-HT functions. Tryptophan, the natural amino acid precursor in 5-HT biosynthesis, increases 5-HT synthesis in the brain and, therefore, may stimulate 5-HT release and function. Since it is a natural constituent of the diet, tryptophan should have low toxicity and produce few side effects. Based on these advantages, dietary tryptophan supplementation has been used in the management of neuropsychiatric disorders with variable success. This review summarizes current clinical use of tryptophan supplementation in neuropsychiatric disorders.
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PMID:L-tryptophan in neuropsychiatric disorders: a review. 130 30

The effects of depletion of the serotonin precursor, L-tryptophan, on the threshold and tolerance to cold pressor pain, and the analgesic effect of morphine (10 mg intramuscularly), were tested in a double blind trial on human volunteers. Effects on mood were also assessed using the Profile of Mood States and the Addiction Research Center Inventory (ARCI) Scales. To deplete tryptophan, subjects were fed a tryptophan-deficient amino acid mixture 4.5 h before morphine was administered. Controls received the mixture with tryptophan, which is equivalent to a nutritionally balanced protein. The tryptophan-deficient meal reduced plasma tryptophan more than 70% but had no effect on threshold or tolerance to cold pressor pain. After morphine, tolerance to cold pressor pain increased in controls. Tryptophan depletion abolished this analgesic effect. Pain threshold was not altered by morphine. In subjects with normal tryptophan, the analgesic effect of morphine was predicted by the level of plasma morphine-6-glucuronide, but not by the level of morphine. Morphine increased scores on the LSD scale of the ARCI, but had no effect on other measures of mood. Tryptophan depletion also failed to alter mood in these subjects, who had unusually low depression scores before tryptophan depletion.
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PMID:Acute tryptophan depletion blocks morphine analgesia in the cold-pressor test in humans. 141 Jan 47

A retrospective study (1985-1989) of patients suffering from diffuse fasciitis with eosinophilia revealed that five of eight patients had taken L-tryptophan-containing drugs before the onset of the disease. In addition, since this drug-disease association was first described five patients have been diagnosed during the year 1990. All ten patients developed peripheral eosinophilia, myalgia and deep skin involvement indistinguishable from eosinophilic fasciitis. Corticosteroids were able to reduce the pain and inflammatory parameters, but did not prophylactically improve the long-standing sclerodermalike skin thickening. In 2/5 patients with symptoms longer than 1 year, low-dose corticosteroid maintenance therapy has been continuously required to control joint and muscle pain.
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PMID:[Eosinophilia-myalgia syndrome. Clinical aspects and follow-up of 10 patients]. 150 2

To test the hypothesis that plasma tryptophan and/or its transport ratio is decreased in primary fibromyalgia (PF), we measured plasma tryptophan and its transport ratio in 29 patients with PF and 30 healthy controls without significant pain, in a blinded manner. Twenty-one other amino acids were also similarly analyzed among these study subjects. Transport ratio of tryptophan was found to be significantly (p less than 0.01) decreased in PF compared with the control group (0.09 +/- 0.02 vs 0.10 +/- 0.02). Plasma tryptophan level was lower in PF (45 +/- 10 nmol/ml) than in healthy controls (51 +/- 15 nmol/ml), showing a trend towards significance (p less than 0.09). Additionally, plasma histidine and serine levels were found to be significantly (p less than 0.01) lower in patients with PF than in controls. Our results suggest that a decreased brain serotonin level, as possibly reflected by a decreased transport ratio of plasma tryptophan, may play a pathophysiologic role in PF.
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PMID:Plasma tryptophan and other amino acids in primary fibromyalgia: a controlled study. 155 7

The use of dietary metabolic precursors to neurotransmitter in the management of chronic pain patients has received critical attention for several years. As pain evolves from acute to chronic, different neuronal pathways are used and diverse areas of the brain become involved in pain perception and modulation. The serotonergic system serves as a useful model for understanding the effect of metabolic precursors. Oral L-tryptophan administration decreases the perception of pain, appearing to act synergistically with the enkephalins and endorphins. Drugs that either increase the serotonin level or block reuptake are associated with decreased pain perception, increased pain threshold, and improved sleep. From a therapeutic standpoint, dietary modification would appear to be attractive, due to its low economic basis, decreased risk of addiction and dependence, as well as simplicity. However, potential risk from toxicity is only recently being recognized, along with difficulty in reliability of analgesic effect from one patient to another. Currently, L-tryptophan is unavailable for therapeutic use in the United States and is not recommended implicitly or explicitly by the author because of its potential health risk.
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PMID:Toward an understanding of the rationale for the use of dietary supplementation for chronic pain management: the serotonin model. 168 35


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