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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

The forebrain serotonin (5-HT) concentrations of rats with lesions in the median (M; n equal to 5), dorsal (D; n equal to 5), and both (DM; n equal to 6) midbrain raphe nuclei were, respectively, 22, 48, and 70% lower than in control animals (n equal to 10). The lesion and control groups, however, did not evidence differences in pain sensitivity as measured by the flinch-jump technique. On the other hand, of the animals tested, those with M (n equal to 3) and DM (n equal to 4) lesions required more trials than controls (n equal to 6) to acquire a one-way avoidance response. D lesion rats (n equal to 2) did not differ from controls in one-way avoidance learning, except in terms of prolonged escape latencies during the first three trials. The previously reported increased sensitivity to painful stimuli subsequent to medial forebrain bundle lesions or para-chlorophenylalanine administration, therefore, does not appear to be due exclusively to disruption of ascending 5-HT fibers originating in the dorsal and median raphe nuclei. The effects of midbrain raphe lesions of avoidance learning, furthermore, depend on lesion locus, and are not due to either hypo- or hyperalgesia.
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PMID:Response to electric shock in rats: effects of selective midbrain raphe lesions. 12 65

Depletion of telencephalic serotonin (5-HT) content by medical forebrain bundle lesions, which interrupt the ascending serotonergic pathways or by DL-p-chlorophenylalanine produces an increased sensitivity to pain as measured by the flinch-jump, stabilimetric, or hot-plate methods. Examination of the effects of a number of other lesions and drugs indicated that dopamine, norepinephrine and acetylcholine are not involved in pain sensitivity. Dosages of 75 mg/kg DL-5-hydroxytryptophan(5-HTP), 37.5 mg/kg L-5-HTP or 50 mg/kg Ro 4-4602 (NI-(DL-seryl)-N2-(2,3,4-trihydroxybenzyl)hydrazine) plus 37.5 mg/kg L-5-HTP administered to medical forebrain bundle lesioned rats returned both the telencephalic content of 5-HT and the pain threshold to normal values. Injection of 37.5 mg/kg of D-5-HTP or an equimolar dose of L-dopa had no effect on pain threshold. Normal animals display increased sensitivity to pain and decreased 5-HT contents in frontal pole, hippocampus, and amygdala during dark as compared to light hours. All three of these telencephalic areas are innervated by the ascending serotonergic pathways, and cells in these areas show inhibition of firing following the iontophoretic application of 5-HT. Taken together these data suggest that the serotonergic system normally acts to inhibit the effects of painful stimuli. A review of a variety of behavioral effects of 5-HT depletion including an enhanced response to lysergic acid diethylamide and amphetamine suggests that the ascending serotonergic system may have a general role in the inhibition of arousal, rather than a specific role with respect to various categories of behavior.
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PMID:Behavioral correlates of serotonin depletion. 12 7

In the rat, oxotremorine increases the threshold for vocalisation after-discharge (affective component of pain reactions) dose dependently at subtremor doses (30-67 mug/kg s.c.). Doses of 225-506 mug/kg were needed to elevate the thresholds for vocalisation and motor response. 1-Tryptophan, PCPA, alpha-methyl-p-tyrosine, 1-Dopa, pimozide and LSD-25 did not affect the antinociceptive activity of oxotremorine, while phenocybenzamine slightly increased the threshold for vocalisation. Oxotremorine did not change the endogenous brain concentrations of noradrenaline and dopamine or 5-HT but decreased that of 5-HIAA in all brain regions at the time of maximal analgesia. The decrease of 5-HIAA was still present after pretreatment with probenecid. After inhibition of tyrosine hydroxylase, oxotremorine accelerated the depletion of dopamine in telencephalic cortex during maximal antinociceptive activity and of noradrenaline in all brain regions at a time when this activity had vanished. Atropine significantly antagonized the analgesic activity of oxotremorine. It is concluded that oxotremorine antinociceptive activity in the rat is related to a cholinergic compoent, while a monoaminergic component is not directly involved.
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PMID:Antinociceptive action of oxotremorine and regional turnover of rat brain noradrenaline, dopamine and 5-HT. 23 55

Facial neuralgia appears in a variety of forms which have different fundamental pathophysiological mechanisms. Of decisive importance are neuralgias with sensitive trigeminal, intermediate (sensory root), glossopharyngeal and vagus nerves which are caused by functional disturbances or damage to the nerve. In addition, projected or referred pain occurs in intracranial and cervical affections. A vascular origin may be assumed for Horton's neuralgia. This periodic paroxysmal and unilateral facial neuralgia is related to migraine. Serotonin, histamine and plasma kinin may be important eliciting factors; the concomitant symptoms of lachyrmation and rhinorrhea, reddening of the eyes and the face and a transitory Horner's syndrome suggest participation of the sympathetic and parasympathetic systems. Consideration of the previously known pathophysiological mechanisms permits a differentiated therapy for the various facial neuralgias.
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PMID:[Pathophysiology of facial neuralgia (authors' transl)]. 30 39

In order to clearly understand the synovial metabolic pathway of 5-HT, which is interesting as an inflammatory mediator and a pain producing substance, in patients with RA and with OA, determinations were made of 5-HIAA levels and of the activities of MAO-A and MAO-B, in the synovial fluid and the blood. With respect to 5-HIAA levels, there was no significant difference in the synovial levels between patients with RA and those with OA, although higher values were obtained in the plasma of patients with RA. A correlation was found between synovial and plasma levels in both diseases. In patients with RA, 5-HIAA levels tended to increase in both levels of the synovial fluid and the plasma in higher stages. The activities of MAO-A and MAO-B in the synovial fluid were found to be lower in patients with RA than in those with OA. The MAO-B activity in the synovial fluid increased in higher stages and correlated with ESR in patients with RA. In patients with RA the efflux of 5-HIAA from the synovial fluid was reduced. No remarkable changes occurred in the permeability of 5-HIAA. The ability to inactivate 5-HT was lower than in OA. The determination of synovial MAO-B activity is useful in diagnosing the status of the patient with respect to rheumatoid arthritis.
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PMID:Serotonin metabolism and its enzymic activities in joint diseases. 45 40

Clomipramine is the most potent 5-HT reuptake blockade agent among the antidepressants. A comparison between the effect of clomipramine and a less powerful 5-HT reuptake blockade agent (amitriptyline) could test the hypothesis that brain 5-HT is a mediator of pain sensation. Groups of patients of either sex, with pain indication of trigeminal neuralgia, tension headache or postherpatic neuralgia, received doses of clomipramine or amitriptyline in a single blind clinical experiment. The results after three months of treatment showed that clomipramine: (1) was better than amitriptyline in treating trigeminal neuralgia; (2) tended to be better in the treatment of tension headache; and (3) amitriptyline is better in treating postherpatic neuralgia. Clomipramine was better tolerated. The results support the hypothesis that in certain pain situations, clomipramine exerts a beneficial effect, not only because of its effect on the depression and anxiety level of the patient, but also via its effects on the 5-HT brain system.
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PMID:Clomipramine and amitriptyline in the treatment of severe pain. 48 62

Serotonin like M-serotonin blocking agent morphine and D-serotonin blocking agent diethalamide of lysergic acid is shown by the method of intravenous microinjections to lower and T-serotonin blocking agent tipindol--to increase the amplitude of primary responses from the dental areas of the brain cortex arising in stimulation of the dental pulp. It is suggested that the seroninergic system of the brain can through the intermediary of the M- and D-serotonin-receptors raise the activity of adrenergic and lower the activity of M-cholinergic structures participating in the formation of the functional system of pain reactions. An opposite effect can be accomplished through the medium of the T-serotonin receptors.
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PMID:[Effect of serotoninergic substances on the brain potentials evoked by stimulation of the dental pulp]. 62 86

In protriptyline (25 mg/kg) pretreated rats stereotactic 5,7-dihydroxytryptamine (5,7-DHT) lesions of the medial plus laternal 5-hydroxytryptamine (5-HE) bundles in the mesencephalon increased the 5-HT fluorescence in these bundles, and reduced the in vitro uptake of [3H] 5-HT in the hypothalamus to 16% of control values after 2 mug 5,7-DHT/4mul and 12% after 4 mug 5,7-DHT/4mul, and in the cortex cerebri to 35 and 34% of control values, respectively. Selective lesion of the medial 5-HT bundle reduced [3H] 5-HT uptake both in hypothalamus and in cortex cerebri to 45-48% of control values, while selective lesion of the lateral 5-HT bundles significantly reduced [3H] 5-HT uptake only in cortex (to 73-75%). No significant change was observed in [3H] noradreanaline uptake after any injection, or in [3H] 5-HT uptake after vehicle injections. Locomotor activity in an open field 3-10 days postoperatively was significantly reduced by lesions of the medial plus lateral 5-HT bundles. 5-Hdroxytryptophan (50 mg/kg) and a peripheral decarboxylase inhibitor (MK 486, 75 mg/kg) 17 days postoperatively induced a pronounced behavioral "5-HT syndrome" in these rats with medial plus lateral lesions but not in controls. Pain sensitivity, as measured by the hot plate test, was not changed by any lesion, even when tryptophan hydroxylase was partly inhibited with alpha-propyldopacetamide (100 mg/kg). Morphine analgesia and acquisition of a one-way avoidance response also were unchanged. Apomorphine (2 mg/kg)-induced locomotor activity and stereotyped behavior, as measured in an Animex activity meter, were not significantly different from control values in the 5,7-DHT groups. It was concluded that the medial 5-JT BUNDLE INNERVATES BOTH THE HYPOTHALAMUS AND THE CORTEX CEREBRI AND THE LATERAL 5-HT bundle mainly the cortex. These ascending 5-HT neurons are involved in maintaining open field ambulation. No wupport was obtained for the view that they are involved in pain mechanisms, in morphine-induced analgesia, in apomorphine-induced motor behavior, or in one-way avoidance learning.
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PMID:Behavioral effects of 5, 7-dihydroxytryptamine lesions of ascending 5-hydroxytryptamine pathways. 94 13

Animal and clinical pharmacological studies show in certain vascular beds a biphasic action [potentiation and inhibition of serotonin (5-HT) responses] of some anti-migraine drugs, such as ergotamine, methysergide and more recently Org GC 94. Potentiation occurs at therapeutic drug concentrations. The present investigations seem to support the 5-HT theory of migraine and other essential headaches. In this theory, anti-migraine drugs, such as ergotamine, methysergide, pizotifen, and Org GC 94 could reduce the occurrence of pain in migraine and other esscutial headaches by acting as partial agonists tending to correct a deficiency of central 5-HT concentrations or turnover.
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PMID:Clinical and animal pharmacology of migraine: new perspectives. 97 97


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