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Query: UMLS:C0344307 (analgesia)
 28,200 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effect of various doses of acute morphine on both analgesia and 5-hydroxytryptamine (5-HT) synthesis in the brain and the spinal cord has been studied in rats rendered tolerant by chronic administration of the analgesic. In morphine-tolerant rats, the incorporation of tritiated-L-tryptophan (TRP) in the brain and the spinal cord was higher than in non-tolerant rats, but there was no significant difference in the synthesis rate of the newly formed 5-HT between the two groups. An acute dose of morphine (10 mg/kg) which induced a powerful analgesia and a large increase in 5-HT synthesis in non-tolerant rats, did not produce analgesia nor changes in 5-HT synthesis in tolerant rats. Higher acute doses of morphine which restored analgesia in tolerant rats, induced a discrete increase in [3H]TRP incorporation and a marked increase in 5-HT synthesis in the spinal cord of these animals. The same doses significantly increased [3H]TRP incorporation in the forebrain but did not modify 5-HT synthesis. These results show that tolerance to morphine is associated with a decrease in the effects of the drug on 5-HT synthesis in the spinal cord and the brain and tend further support to the hypothesis that an enhancement of 5-HT synthesis in the spinal cord, induced independently of modifications of the availability of TRP, is associated with the analgesic effect of morphine.
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PMID:The relationship between morphine analgesia and the activity of bulbo-spinal serotonergic system as studied by tolerance phenomenon. 627 44

Recent studies have shown that while the analgesic responses induced by certain stressors appear to be related to morphine analgesia, the analgesic responses to other stressors do not. Para-chlorophenylalanine (PCPA), a potent tryptophan-hydroxylase inhibitor has been shown to decrease both basal pain thresholds and morphine analgesia on the flinch-jump test. To assess further the relationship between morphine and stress-induced analgesia, PCPA's effect upon the analgesic responses to cold-water swims, 2-deoxy-D-glucose, inescapable foot shock and morphine were determined using the flinch-jump and tail-flick tests. PCPA, which produced an 85% depletion of brain serotonin, significantly decreased jump thresholds while significantly increasing tail-flick latencies. Similarly, while morphine analgesia was decreased by PCPA on the flinch-jump test, it was not affected on the tail-flick test. The analgesic jump thresholds induced by cold-water swims and 2-deoxy-D-glucose as well as the increase tail-flick latencies induced by foot shock were unaffected by PCPA. These results are discussed in terms of PCPA's differential effects upon basal nociception and morphine analgesia and in terms of further dissociation between morphine and stress-induced analgesia.
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PMID:Stress and morphine analgesia: alterations following p-chlorophenylalanine. 645 44

The effects of a nociceptive peripheral stimulus and/or morphine upon endogenous tryptophan levels (TRP), specific activity of tryptophan (S.A. of TRP) and serotonin (5-HT) synthesis in the dorsal and ventral spinal cord, the brainstem and the forebrain were investigated in anaesthetized rats. Whereas endogenous TRP and S.A. of TRP were not found to be affected by any of the manipulations described below, 5-HT synthesis was markedly altered. The application of a prolonged and intense nociceptive electrical stimulus to the tail induced a rise in 5-HT synthesis which was dependent on the part of the CNS considered, with the dorsal cord being the most sensitive (25%), the ventral cord and the brainstem being effected to a lesser extent (14% and 16% respectively), and the forebrain not being affected significantly. By contrast, the application of a prolonged and innocuous electrical stimulus on the tail was not followed by any detectable changes in 5-HT synthesis. Morphine administration (1 mg/kg; i.v.) did not significantly alter 5-HT synthesis in the four CNS regions considered. Nevertheless, the same morphine dose did induce a highly significant (P less than 0.005) reduction in the increase in 5-HT synthesis induced by the nociceptive stimulus, both in the dorsal cord and in the brainstem. Such an effect was not seen in the ventral cord. The specificity of these morphine effects was demonstrated by their naloxone reversibility; on the other hand, naloxone alone failed to modify the stimulus-induced increase in 5-HT synthesis seen in the dorsal cord and the brainstem. The results, particularly those concerning the dorsal cord, are discussed with reference to pain mechanisms and morphine analgesia. They suggest that peripheral nociceptive messages induce an increased activity in some bulbo-spinal 5-HT pathways and that a low dose of morphine can counteract such an effect. It is proposed that exogenous opiates exert a complex regulation of bulbo-spinal 5-HT pathways. Functional significances of these processes are discussed.
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PMID:Increase in 5-HT synthesis in the dorsal part of the spinal cord, induced by a nociceptive stimulus: blockade by morphine. 672 43

Morphine analgesia measured by the tail withdrawal test was examined in rats that were either restrained or left free during testing. It was found that restraint potentiated morphine analgesia and decreased the latency of the peak analgesic effect. Methysergide, a serotonin antagonist, and valine, which prevents the increase in brain tryptophan induced by restraint, blocked the effect of restraint on morphine analgesia. Valine did not alter analgesia in unrestrained rats. An increase in brain tryptophan uptake induced by stress is suggested as a possible mechanism by which stress can interact with pain modulation systems.
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PMID:Evidence that stress augments morphine analgesia by increasing brain tryptophan. 672

Studies are described on the effect of plasma tryptophan changes on brain 5HT synthesis in man and rat. Results show that human brain 5HT synthesis is influenced by the supply of tryptophan to the brain. This is indicated by: (a) significant correlations between plasma free tryptophan and CSF 5HIAA concentrations; (b) raised cortical 5HT concentrations after infusing tryptophan. In rat experiments, determinations of brain tryptophan uptake from a bolus of plasma injected into the carotid artery showed: (a) increased uptake when bolus free tryptophan was raised and total tryptophan kept constant; (b) unchanged uptake when bolus free tryptophan was kept constant and total tryptophan decreased. Brain tryptophan uptake from a buffer bolus was decreased by large neutral amino acids. Plasma total tryptophan could be rapidly decreased and free tryptophan increased by briefly disturbing food deprived rats. When free tryptophan concentration rose markedly there was an associated increase of brain tryptophan and 5HT turnover. Studies of shock provoked analgesia in rats and cortical evoked potentials in man both suggest that physiological variations of serotonergic activity are sufficient to influence these measures. This raises the possibility that moderate changes of tryptophan supply to the brain could, in some circumstances, alter serotonergic activity.
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PMID:Influence of plasma tryptophan on brain 5HT synthesis and serotonergic activity. 731 2

The effects of L-tyrosine (L-TYR) on the analgesic activity of several opioids were determined utilizing a hot-plate test. L-TYR (200 mg/kg) significantly potentiated (P < .05) the analgesic activity of morphine sulfate (10 mg/kg) and codeine sulfate (30 mg/kg). The opioid-induced analgesia and its potentiation by L-TYR was abolished by naloxone pretreatment. Increasing the dose of L-TYR (25-200 mg/kg) resulted in a dose-dependent potentiation of morphine-induced analgesia. The observed potentiation was positively correlated with increases in brain TYR concentrations; blockade of L-TYR uptake into the brain by the coadministration of L-valine attenuated this potentiation. With the exception of L-tryptophan, all other L-amino acids, as well as D-TYR, failed to mimic the potentiating action of L-TYR. As determined by alpha-methyl-p-TYR pretreatment, the L-TYR-induced potentiation was dependent upon increased catecholamine synthesis. These results demonstrate that L-TYR dose dependently potentiates the analgesic activity of opioids and are consistent with the requirement of the central conversion of L-TYR to catecholamines via TYR hydroxylase for this response.
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PMID:L-tyrosine potentiation of opioid-induced analgesia utilizing the hot-plate test. 801 63

The effects of the methyl esters of L-tyrosine (L-Tyr-OMe) and L-tryptophan (L-Trp-OMe) on the analgesic action of trans-3,4-dichloro-N-methyl-N-[2-(1-pyrrolidin)cyclohexyl]-benzene acetamide methane sulfonate (U-50,488H), a kappa-opioid receptor agonist, were determined in male Swiss-Webster mice using the tail-flick test. Intraperitoneal injections of U-50,488H produced a dose-dependent analgesic response. The analgesic response to all doses of U-50,488H was potentiated by L-Tyr-OMe at 200 mg/kg injected intraperitoneally 30 min prior to the injection of U-50,488H. The effect of various doses of L-Tyr-OMe (50, 100 and 200 mg/kg) on the analgesia produced by 20 mg/kg of U-50,488H was also determined. The lowest dose (50 mg/kg) of L-Tyr-OMe did not modify U-50,488H-induced analgesia but the two higher doses enhanced it significantly. L-Tyr-OMe by itself at all the doses tested had no effect on the tail-flick latency. L-Trp-OMe (200 mg/kg) enhanced the analgesic action of 10 and 20 mg/kg doses of U-50,488H but not that induced by a 5 mg/kg dose. The analgesia induced by 20 mg/kg of U-50,488H was potentiated by L-Trp-OMe at 100 and 200 mg/kg but not by a 50 mg/kg dose. L-Trp-OMe by itself also did not alter the tail-flick latency. Previously, the studies in this laboratory have shown that L-Try-OMe potentiates morphine, a mu-opioid receptor agonist-induced analgesia.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Enhancement of a kappa-opioid receptor agonist-induced analgesia by L-tyrosine and L-tryptophan. 808 53

The effect of oral feeding of a commercial preparation of essence of chicken (Brand's Essence of Chicken, BEC) on the level of 5-hydroxyindole acetic acid (5-HIAA) in the cerebrospinal fluid (CSF) of the rat was investigated. BEC, when fed to the rat for a period of 3 days, significantly increased the CSF level of 5-HIAA in seven out of 12 animals studied. As the level of CSF 5-HIAA is taken as an indication of 5-hydroxytryptamine (5-HT) activity in the brain, it is possible that BEC increased brain 5-HT activity. This increase was not due to the ingestion of tryptophan, the primary precursor of 5-HT, because BEC contains undetectable level of tryptophan. The data indicate that by causing an increase in brain 5-HT activity, consumption of BEC may lead to the activation of 5-HT-dependent physiological process like sleep improvement, mood elevation, analgesia, facilitation of motor output and regulation of circadian rhythm. However, such a possibility remains to be further investigated.
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PMID:Effect of oral feeding of essence of chicken on the level of 5-hydroxyindole acetic acid in the cerebrospinal fluid of the rat. 913 74

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

Male Sprague-Dawley rats weighing 150-200 g were given doses of tryptophan methyl ester or its metabolites; kynurenine sulphate, kynurenic acid, xanthurenic acid, quinolinic acid, anthranilic acid methyl ester or picolinic acid methyl ester. Doses administered intraperitoneally were 50, 100, 200, 300, 400 and 600 mg kg-1. Pain sensitivity was assessed using the hotplate and tailflick methods at 30 min before and at 30-min interval after the injection of test compounds. The administrations of tryptophan, kynurenic acid, quinolinic acid, anthranilic acid, xanthurenic acid, picolinic acid, and kynurenine were associated with analgesia. Animals given 300 or 600 mg kg-1 of tryptophan exhibited a significant decrease (P<0.05; P<0.01, respectively) in pain sensitivity with the hotplate test. l-Kynurenic acid (300 mg kg-1) produced analgesia (P<0.01) 30 min after drug administration. Quinolinic and anthranilic acids both produced prolonged decrease in pain sensitivity (P<0.05) using the tailflick test. These results indicate that tryptophan and some of its metabolites possess analgesic properties.
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PMID:The analgesic effects of tryptophan and its metabolites in the rat. 977 87


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