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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 roles played by the cerebral monoamines (dopamine, noradrenaline and serotonin) in stimulation-produced analgesia (SPA) have been investigated in the rat employing the tail flick test. SPA was elicited through bipolar electrodes chronically implanted in the mesencephalic periaqeductal gray matter, an area previously shown to yield potent and reliable analgesic effects. Four approaches were used to alter transmission in monoamine pathways. (1) Depletion of monoamines by administration of tetrabenazine (TBZ), p-chlorophenylalanine (PCPA), alpha-methyl-para-tyrosine (AMPT), or disulfiram. (2) Replacement of depleted monoamine stores by appropiate precursors (5-HTP or L-DOPA) in combination with a peripheral decarboxylase inhibitor. (3) Potentiation of monoamine systems by administration of precursors to previously untreated animals or by administration of a dopamine receptor stimulator, apomorphine. (4) Blockade of catecholamine receptors by haloperidol or of dopamine receptors by pimozide. These four approaches yielded internally consistent results. Depletion of all 3 monoamines (TBZ) led to a powerful inhibition of SPA. Original levels of SPA were restored by injection of either 5-HTP or L-DOPA. Specific depletion of serotonin (PCPA) caused a reduction in SPA, whereas elevation of serotonin levels (5-HTP) caused an increase in SPA. Dopamine receptor blockade (pimozide) decreased SPA, whereas the precursor (L-DOPA) and a dopamine receptor stimulator (apomorphine) increased SPA. On the other hand, selective depletion of noradrenaline (disulfiram) caused an increase in SPA; and at a time when noradrenaline levels are depressed and dopamine levels are elevated (AMPT + L-DOPA), SPA was seen to be particularly enhanced. thus, dopamine and serotonin appear to facilitate SPA, whereas noradrenaline appears to inhibit it. When a general catecholamine receptor blocker (haloperidol) was employed, SPA was diminished, suggesting that the influence of dopamine in SPA is greater than that of noradrenaline. Most of the drugs used in this study significantly altered SPA at doses which left baseline tail flick latency unaffected. It would appear, therefore, that SPA has a neural substrate at least partly independent of that underlying baseline pain responsiveness. Consideration is given to various ascending and descending monoamine system as possible component paths in this neural substrate of SPA. Finally, the present results are discussed in relation to studies by others on the site and mechanism of morphine's analgesic action. Some striking parallels between SPA and morphine analgesia are noted. These suggest the existence of a common pain-inhibitory system in the brain activated by morphine and by focal electrical stimulation.
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PMID:Monoaminergic mechanisms of stimulation-produced analgesia. 12 41

Clonidine is able to increase the threshold for vocalisation during stimulation and the threshold for vocalisation after withdrawal of stimulus (vocalisation afterdischarge). These effects of clonidine were investigated after treatment of rats with drugs influencing central monoaminergic and cholinergic mechanisms. Chlorpromazine, atropine and p-chlorophenylalanine increased the activity of clonidine at both thresholds while phenoxybenzamine and reserpine pretreatment increased the activity at the thresholds for vocalisation only. Yohimbine decreased clonidine activity at both thresholds while 5-HTP and alpha-methyl-p-tyrosine decreased the effects at the threshold for vocalisation afterdischarge. Naloxone did not change the activity of clonidine at either pain response studied. It is concluded from the present findings that influence from several neuronal systems modulate the antinociceptive action of clonidine. The inhibition of the medullary nociceptive response after clonidine might be connected to a decreased activity of noradrenergic neurons. Endogenous noradrenaline seems to be of minor importance in mediating this effect. It is moreover shown that decreased cholinergic receptor activity enhances clonidine antinociceptive action on both medullary and diencephalic-rhinencephalic pain responses. The possible involvement of serotonin these functional responses after clonidine is also discussed.
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PMID:Clonidine antinociceptive activity: effects of drugs influencing central monoaminergic and cholinergic mechanisms in the rat. 13 92

Chronic stimulating electrodes were implanted into two separate midbrain sites in rats. One site was the dorsal central gray area (DCG), where electrical stimulation produced frantic, escape-seeking behavior which grossly appeared fear-like and/or pain-like. The other site was in the ventral reticular formation (VRF), where stimulation produced a stereotyped circling response. Stimulation at both sites was aversive in that these animals would bar press for escape in a decremental bar-pressing paradigm. In this paradigm, each bar press decremented the current by five per cent of the initial current level. Following the acquisition of stable baseline decremental bar-pressing performance, animals were given injections of either the serotonin-depleting drug, para-chlorophenylalanine (PCPA), or the catecholamine-depleting drug, alpha-methyl-para-tyrosine (AMPT). Control animals received normal saline. Compared to saline control animals, PCPA-injected DCG-stimulated animals showed a marked increase in decremental bar pressing, whereas VRF-stimulated animals showed no change. AMPT-injected VRF-stimulated animals showed a marked decrease in decremental bar pressing, but the DCG-stimulated animals were not affected. These results suggest that escape behavior from electrical stimulation of midbrain sites is mediated by more than one neural system.
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PMID:Anatomic and pharmacologic differences between two types of aversive midbrain stimulation. 15 Aug 78

Brain catecholamine metabolism was monitored by distribution of labelled noradrenaline (3H-NA) after intraventricular injection to intact and adrenalectomized rats. The adrenalectomy produced an increased disappearance rate of the labelled pool in the hypothalamus, hippocampus and neocortex. These changes could be prevented by hydrocortisone pretreatment. Painful stimuli resulted in an increased disappearance of the labelled pool in both intact and adrenalectomized rats. The implantation of hydrocortisone into the tuberoinfundibular region prevented the stress-induced changes of the catecholamine metabolism. Intraventricular administration of ACTH1-24 and ACTH4-10 produced a significant increase of the disappearance rate in different brain regions of adrenalectomized rats. The blocking of catecholamine synthesis by intraventricular injection of alpha-methyl-m-tyrosine resulted in a marked decrease of the labelled pool but did not prevent the ACTH-induced decrease of the tracer pool. On the other hand, the blocking of monoamine-oxydase activity by Pargyline led to a marked increase of the labelled pool but intraventricular administration of ACTH led to an increase of the disappearance rate. The mechanism of ACTH action on brain catecholamine metabolism is still obscure, however, an increased release of the NA to ACTH peptides is very likely in the light of the present observations.
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PMID:Effect of ACTH and its fragment on brain catecholamines in intact and adrenalectomized rats. 18 19

Painful stimuli led to a decrease of the radioactive catecholamine pool in adrenalectomized rats. Intraventricular administration of both tritiated noradrenaline and ACTH produced a greater decrease of the labelled catecholamine pool than in the control adrenalectomized rats in 12 to 18 hr following injection. Blocking of monoamino-oxidase activity or biosynthesis by systemic administration of Pargyline or alpha-methyl-tyrosine did not prevent the effect of ACTH on brain catecholamines. It is concluded that ACTH exerts a direct influence on the brain catecholaminergic system and that this effect might be involved in ACTH dependent behavioural responses.
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PMID:Effect of ACTH1-24 and ACTH4-10 on distribution of 3H-noradrenaline in the brain of adrenalectomized rats. 20 66

Endorphins are peptides with opiate-like action synthesized in various tissue, e.g. in intestine and central nervous system. Exact characterization of opioid-specific receptors and sensitive biological test assays for opioids were prerequisites for the discovery of these substances. Met- and leu-enkephalin were the first endorphins discovered. Both are pentapeptides. One of them, namely met-enkephalin (H-Tyr-Gly-Gyl-Phe-Met-OH) is likely to be a fragment of the peptides alpha- and beta-endorphin, both showing opioid-like actions, as well as of beta-lipotropin, a polypeptide showing no opioid-like activity: all these peptides include the pentapeptide met-enkephalin within their molecules. beta-liportropin and ACTH are likely to be fragments of a common precursor. At least both enkephalins (which are studied better as yet than the other endorphins) are supposed to be formed in the soma of the neuron and transported to the nerve ending, where they are released. They seem to have the function of neuromodulator or even of neurotransmitters. The pharmacological actions of endorphins resemble those of "classical opiates", both having e.g. analgesic effects. Both enkephalins are, among various other brain and spinal cord areas, localized in those areas which seem to be of particular relevance for perception and transmission of pain. They might, under certain conditions, play some part in the regulation of pain perception. Furthermore, they seem to be relevant for some neuroendocrine processes. Their relevance in symptoms of schizophrenic psychoses seems to be more doubtful. In opiate dependence no significant alterations of endorphin concentrations could be observed as yet.
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PMID:[On the physiology and pharmacology of endorphins (author's transl)]. 22 45

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

In a series of experiments the effects of p-chloroamphetamine (PCA) on shock-elicited aggression in rats were investigated. 15 min after 5 mg/kg PCA, shock elicited aggression was inhibited. 2 h to 4 weeks after PCA, fighting was facilitated. Both the inhibitory and the excitatory effects of PCA were directly related to the dose of PCA (1.5, 2.5 OR 5 mg/kg) and were blocked by pretreatment with p-chlorophenylalanine but not by alpha-methyl-p-tyrosine. PCA-increased pain thresholds 15 min after injection and then decreased pain thresholds over the next 24 h but not thereafter, even though shock-elicited aggression continued to be facilitated. The results are consistent with the idea that inhibition of shock-elicited aggression is associated with enhanced release of serotonin whereas enhancement of shock-elicited aggression is associated with serotonin depletion.
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PMID:p-Chloroamphetamine: short and long term effects upon shock-elicited aggression. 103 73

The term cholecystokinin (CCK) refers to a family of related peptides whose members play hormonal roles in the gastro-intestinal tract. The sulfated octapeptide CCK-8 [Asp-Tyr(SO3H)-Met-Gly-Trp-Met-Asp-Phe-NH2] is also abundant throughout the central nervous system where it satisfies the criteria for a neurotransmitter. CCK interacts with at least two types of receptor called CCK-A and CCK-B receptors. These binding sites can be distinguished on the basis of their affinities for different molecular forms of CCK. Moreover, selective nonpeptide antagonists have been developed for CCK-A and CCK-B receptors. CCK-A receptors occur predominantly at the peripheral level where they are responsible for the digestive effects of CCK: intestinal and biliary smooth muscle contraction, pancreatic enzyme secretion, trophic effects on gastric and intestinal mucosa and regulation of feeding. Some brain CCK-receptors belong to the A-type, but the majority of them are CCK-B receptors. High densities of brain CCK-B receptors are present in cortical and limbic areas such as the amygdala and the hippocampus. At the peripheral level, CCK-B receptor antagonists are active on gastrin receptors, and these two receptors are similar if not identical. Experimental evidence suggests involvement of brain CCK processes in 4 domains: modulation of dopaminergic function, control of pain sensation, anxiety and memory formation. Thus, CCK-B antagonists may be useful to treat certain neuropathological conditions associated with CCK dysfunction.
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PMID:[Cholecystokinins and their receptors. Functional aspects]. 130 46


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