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

1. The effect of morphine on the histamine content of the mouse brain has been investigated. The changes in the brain histamine level have been related to morphine-induced analgesia and morphine-induced changes in locomotor activity. 2. With doses of morphine between 1 and 5 mg/kg there was a significant increase in histamine levels. The time required to produce a maximal rise in the brain histamine level with 5 mg/kg of morphine was 15 min. 3. There was a significant decrease in brain histamine levels with doses of morphine between 7-5 and 100 mg/kg. The time at which the greatest decrease was produced with 50 mg/kg was 30 min. 4. The time couse of the alteration of brain histamine by morphine did not correlate with its antinociceptive activity. Both the 5 and 50 mg/kg doses of morphine produced analgesia in mice whereas brain histamine levels were increased and decreased, respectively. 5. Pretreating mice with compounds which modify histaminergic function did not modify the antinociceptive action of morphine. 6. Morphine produced a biphasic effect on locomotor activity when the dose was increased from 0-5 through to 100 mg/kg. Doses up to 2-5 mg/kg caused a reduction of activity and doses above this produced significant increases. 7. There appears to be an inverse relationship between the morphine-induced changes of brain histamine and the morphine-induced changes in locomotor activity.
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PMID:Effects of morphine on brain histamine, antinociception and activity in mice. 1 Jan 13

We have recently demonstrated that prenatal administration of morphine to the rat results in tolerance to the analgesic effects of morphine in the offspring at 3 to 11 weeks of age. To extend these findings, levorphanol or dextrorphan was administered to female CFE rats during days 5 to 12 of gestation. Control animals were injected with 0.9% saline on the same schedule. At 5 weeks of age all offspring were tested with graded doses of morphine in the hot-plate test for analgesia. Morphine produced a dose-related increase in analgesia in all offspring, but the effect of morphine in the offspring of levorphanol-treated females was significantly reduced compared to the offspring of saline-treated females; the analgesic effect of morphine did not differ between the offspring of the dextrorphan- and saline-treated females. The analgesic effect of morphine remained reduced in 9-week old offspring of levorphanol-treated females compared to the corresponding offspring of females that had received saline. Diminished analgesic activity of morphine in the offspring of levorphanol-treated females compared to the offspring of females that had received dextrorphan or saline was still observed even when the offspring were rendered tolerant to morphine by daily drug injections over a period of 5 days. Thus, the protracted tolerance to the analgesic effects of morphine can also be produced by a morphine congener (levorphanol), but not by its analgesically inactive (+) isomer (dextrorphan).
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PMID:Prenatal administration of levorphanol or dextrorphan to the rat: analgesic effect of morphine in the offspring. 1 48

The nociceptive reflex activity and analgesic effect of morphine were studied in rats using the hind paw stimulation test. The stimulation threshold was significantly increased in animals with bilateral destruction of the locus coeruleus (LC), and was reduced after lesion of the dorsal raphe nucleus (DR). LC lesions produced a selective lowering of noradrenaline (NA) content in the forebrain, while DR lesions resulted in a reduction in serotonin levels. Lesioning both LC and DR significantly reduced both NA and serotonin contents even when the stimulation threshold was not altered. Morphine produced a significant and dose-dependent elevation of the stimulation threshold in sham-operated animals, while morphine analgesia was almost completely inhibited by destruction of LC, DR and both the nuclei. These results imply that a depression of LC-mediated noradrenergic tone results in a decreased sensitivity to painful stimuli, whereas a reduction of raphe-derived serotonergic tone produces the opposite effect against LC. It is suggested, however, that both of these monoamines from the LC and DR are necessary for the analgesic effect of morphine.
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PMID:Attenuation of morphine analgesia in rats with lesions of the locus coeruleus and dorsal raphe nucleus. 1 37

Morphine, the principal alkaloid of "papaver somniferum" is the reference substance of central analgesics, the parmacodynamic constants of which are: analgesia and the possibility of addiction. Respiratory depression is, for many of them, a grave side-effect. At the present time, no substance in this category is fully satisfactory and all may result in dependence. Equi-analgesic doses of dextromoramide, phenoperidine and Fentanyl are less than those of morphine, whilst those of pethidine and pentazocine are higher. Study of the pharmacokinetics of these various substances indicates no common elements, and it is difficult to consider that the analgesic action is proportional to blood levels. Clinical assessment of the mean duration of action makes it possible to divide morphine derivatives into substances with a very short action (20 to 45 minutes) such as Febtanyl and phenoperidine, and those with a longer action (1 to 4 hours) which includes the majority of the other substances. The analgesic activity of Methoadone lasts for 4 to 6 hours. Morphine antagonists such as Methadone, nalophine, naloxone and naltrexone possess specific problems in terms of their utilization. Pharmacological data concerning theses substances are described.
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PMID:[Pharmacology of morphine and its derivatives (review)]. 2 28

The influences of the dopaminergic system on morphine-induced analgesia and respiratory depression were compared using modulators of dopaminergic activity. Blockade of dopaminergic receptors by haloperidol or pimozide produced a potentiation of morphine analgesia, while stimulation of dopaminergic activity by L-dopa methyl ester inhibited morphine analgesia. Morphine-induced depression of respiratory rate was potentiated by haloperidol and inhibited by pimozide or L-dopa methyl ester. These results suggest that the dopaminergic system plays a modulating role in morphine-induced analgesia, but not in morphine-induced respiratory depression.
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PMID:The effect of dopaminergic modifiers on morphine-induced analgesia and respiratory depression. 3 17

We have studied the interactions between morphine and a dopamine-blocking agent (haloperidol) and a dopamine precursor, L-3,4-dihydroxyphenylalanine (L-dopa). We found that haloperidol potentiated morphine-induced analgesia and enhanced morphine tolerance. Morphine-tolerant mice exhibited enhanced sensitivity to the locomotor excitatory actions of L-dopa. We propose that morphine exerts some of its central nervous actions by first interfering with dopamine-mediated synaptic transmission and then initiating compensatory changes that superficially resemble denervation supersensitivity. These compensatory changes may underlie the excitatory actions of morphine.
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PMID:Dopaminergic mechanisms of opiate actions in brain. 16 29

Inhibition of the electrically induced contractions of the guinea-pig ileum has been shown to be a reliable index to the relative potency of various narcotic analgesics. This property suggests that this preparation might be used as a model in attempts to elucidate the mechanism(s) by which morphine induces analgesia in the central nervous system. Since it has been demonstrated that some adenosine derivative may function as an endogenous inhibitory transmitter in the gut, the effects of adenosine, adenosine triphosphate (ATP) and morphine on the ileum were further characterized and compared. Morphine, adenosine and ATP produce a substantial inhibition of the isometric contractions induced by transmural field stimulation. The inhibition produced by each is antagonized by 2.5 times 10(-7) M tolazoline whereas that produced by ATP is potentiated by 4 times 10(-7) M 5-hydroxytryptamine. The inhibitory effects of morphine and ATP can also be markedly potentiated by two of the several phosphodiesterase inhibitors tested, Ro 20-1724 and dipyridamole. In addition, pretreatment of the ileum with either adenosine, ATP or morphine can produce a significant potentiation of the inhibitory effects of norepinephrine. The above suggests that cyclic adenosine 3',5'-monophosphate may play a role in mediating some of the inhibitory effects produced by exogenous adenosine, ATP and morphine. In addition, the similarities between the effects produced by these substances indicates that the biochemical pathways responsible for mediating the effects of each may share some common elements.
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PMID:Interactions of morphine, adenosine, adenosine triphosphate and phosphodiesterase inhibitors on the field-stimulated guinea-pig ileum. 16 45

Single-dose tolerance to the antinociceptive effect of morphine can be demonstrated using an adequate initial priming dose of morphine and allowing an interval of 48 to 72 hours for its development. The threshold dose necessary to produce tolerance was found to be about 3 to 4 times greater than that for producing analgesia but higher doses of morphine did not enhance further tolerance development. Evidence of tolerance was indicated by the fact that when the antinociceptive response to morphine was assessed by the hot-plate and the tail-flick procedures, a shift in the dose-response curve of morphine to the right occurred after an adequate single priming dose of morphine. Cross-tolerance was evidenced by a decrease in analgetic response to methadone 3 days after a single priming dose of morphine and a decrease in morphine response after a single dose of methadone. The development of single-dose tolerance was inhibited by cycloheximide. Single-dose tolerance was also blocked by 5,6-dihydroxytryptamine and perhaps enhanced by L-tryptophan. Cyclic 3',5'-adensine monophosphate did not affect single-dose tolerance development significantly although the direction was in favor of augmentation. Morphine uptake by the brain was not modified by the development of single-dose tolerance. Physical dependence, as measured by naloxone-precipitated withdrawal jumping, was not observed when single-dose analgetic tolerance was maximal. The results suggest that single-dose tolerance to morphine involves the synthesis of some macromolecule and support previous findings in this laboratroy involving an association with serotonin.
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PMID:Studies on tolerance development to single doses of morphine in mice. 18 57

Prostaglandin E1 (PGE1)-stimulated [3H]3',5'-cyclic adenosine monophosphate ([3H]cAMP) accumulation was studied in a rat brain mince system to determine if stimulation of net [3H]cAMP accumulation could be prevented or reversed by morphine. Incubated minces of whole brain minus cerebellum were prepared from naive, acutely morphine-treated, and morphine-tolerant and withdrawing rats. Basal levels of [3H]cAMP accumulation in the three groups were equal within experimental limits. Morphine addition to the PGE1-stimulated minces did not prevent or reverse stimulation of [3H]cAMP accumulation in any of the three experimental groups. The data do not support the thesis that PGE1-stimulated cAMP accumulation in brain is a locus of opiate action in the phenomena of opiate analgesia, tolerance, and dependence.
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PMID:Absence of morphine antagonism of prostaglandin E1-stimulated [3H]3',5'-cyclic adenosine monophosphate accumulation in a rat brain mince system. 18 21

Experiments were carried out in rats to (1) elaborate upon the sepcificity of drug action in the periaqueductal gray matter (PAG), and (2) to evaluate the posible congruence of PAG sites of morphine-induced and stimulation-produced analgesis (SPA) applied at virtually identical PAG loci. It was demonstrated that the effect of morphine intracerebrally (i,c.) administered into the PAG was not duplicated by other centrally acting agents (chlorpromazine, chlordiazepoxide, pentobarbital or naloxone) administered i.c. at the same PAG site. This selective action of morphine in the PAG was further demonstrated not to be test-bound since morphine significantly altered responding in all four of the analgesiometric tests employed. Thus, multiple i.c. injections of drugs at the same PAG locus were useful in demonstrating site specificity of drug action where behavioral and electroencephalographic methods alone had previously provided ambiguous information. Morphine-induced analgesia and SPA, evaluated at virtually coincident PAG sites, revealed only a general congruence of efficacious loci. The most effective PAG loci for morphine-induced analgesia were not the same as those for SPA; analgesia effected by one analgesia-producing manipulation did not reliably predict that analgesia would also be produced by the other analgesia-producing manipulation at the PAG sites examined. In general, the more efficacious analgesia-producing PAG loci were localized in the ventral-ventrolateral PAG.
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PMID:Evaluation of the periaqueductal central gray (PAG) as a morphine-specific locus of action and examination of morphine-induced and stimulation-produced analgesia at coincident PAG loci. 19 Nov 50


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