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

Reserpine was the most potent, rescinnamine the next and syrosingopine the weakest in the depleting effects on brain amines of rauwolfia alkaloids. After syrosingopine, brain dopamine (DA) was decreased to a smaller degree and with a shorter duration as compared with norepinephrine (NE) and serotonin (5-HT), whereas reserpine elicited a marked and long lasting reduction in these amines. Accordingly, syrosingopine induced a depletion of brain NE and 5-HT without alteration in brain DA content 2-4 days after administration. Repeated administrations of syrosingopine, 2 mg/kg daily for 2 or 4 days, resulted in similar alterations in brain amine levels. This selective depleting effect of syrosingopine on brain amines was potentiated by combined treatment with disulfiram or fusaric acid, a dopamine beta-hydroxylase inhibitor. Under the condition of selective depletion of brain amines induced by repeated administrations of syrosingopine, 2 mg/kg daily for 2 days, the analgesic action of morphine was not affected, whereas reserpine and tetrabenazine antagonized morphine analgesia, concomitant with inducing a depletion of all brain amines. The results suggest that brain DA may be more important than brain NE or 5-HT with regard to the mechanisms by which morpine produces analgesia.
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PMID:Selective depleting effect of syrosingopine on brain catecholamine levels with relation to morphine analgesia in the rat. 0 76

Effects of methyl o-(4-hydroxy-3-methoxycinnamoyl) reserpate (CD-3400) on the central nervous system in mice, rats and cats were investigated, and a comparison was made with such effects of reserpine and rescinamine. Inhibitory effects of CD-3400 on spontaneous motor activity and conditioned avoidance response were weaker and shorter than those of reserpine and rescinnamine. In the experiments of the inhibitory effects of the central actions such as ptosis, hypothermia, decrease in motor ability, potentiation of hexobarbital and taming, reserpine was found to be the most potent followed by rescinnamine and CD-3400, respectively. High doses of CD-3400 exhibited inhibitory effects on methamphetamine-induced hyperactivity in mice and this action was weaker than those of reserpine and rescinnamine. CD-3400, 80-160 mg/kg p.o., showed no significant effects on morphine-induced analgesia, while a slight inhibition was observed on the Straub-tail reaction using morphine. Reserpine, 0.5 mg/kg i.v., resulted in a drowsy pattern in the spontaneous EEG activity and the EEG arousal response was depressed, while with CD-3400, 5 mg/kg i.v., there was no drowsy pattern. CD-3400 as well as rescinnamine and reserpine remarkably depleted 5-HT levels in brain, heart and plasma and the potency of CD-3400, particularly in the brain, was weaker than the potency of reserpine and rescinnamine. These results indicate that CD-3400 is an antihypertensive agent with a low toxicity and a weak central action.
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PMID:[Inhibitory effects of methyl o-(4-hydroxy-3-methoxycinnamoyl) reserpate (CD-3400) on the central nervous system (author's transl)]. 2 46

The phenomenon of tolerance to the analgesic action of tremorine in mice was studied by the hot-plate and tail-clip methods. Reduction in 5-HT levels in brain by parachlorophenylalamine pretreatment decreased the ED50 of tremorine analgesia in tremorine tolerant mice. 5-Hydroxyptophan, L-Dopa or alpha-methyl-para-tyrosine did not influence the analgesic response to tremorine in tremorine tolerant animals. However, theophylline was found to enhance the tolerance to tremorine analgesia. Brain 5-HT and cAMP are probably involved in tremorine tolerance, whereas neither noradrenaline nor dopamine is involved in the phenomenon.
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PMID:Possible involvement of 5-hydroxytryptamine and cyclic-AMP in tolerance to tremorine analgesia in mice. 19 5

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

The effects of lesions of the raphe nuclei on opiate-induced antinociception and brain serotonin (5-HT) levels were investigated. Lesions of the medial raphe nucleus effectively antagonized the analgesic effects of morphine, but not methadone, and lowered brain 5-HT. The decrement in analgesic activity of morphine was reversed by pretreatment with 5-hydroxytryptophan. Lesions of the raphe magnus, a descending 5-HT system, antagonized the analgesic potency of both morphine and methadone. These experiments indicate a differential effect of 5-HT manipulation on opiate-induced analgesia, suggesting a different mechanism of analgesic action for morphine and methadone.
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PMID:Effects of medial raphe and raphe magnus lesions on the analgesic activity of morphine and methadone. 41 64

In vitro effects of d,l-methadone and morphine on [3H]serotonin (3H-5-HT) uptake in rat periaqueductal gray (PAG) slices were investigated. Only methadone had a significant inhibitory effect on 3H-5-HT uptake which was significantly enhanced by naloxone. The systemic administration of methadone did not affect 3H-5-HT uptake in vitro. These data further weaken the possible relationship between narcotic analgesia and blockade of the 5-HT reuptake mechanism.
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PMID:Effect of methadone and morphine on serotonin uptake in rat periaqueductal gray slices. 51 Mar 90

Serotonin depletion or lesions of the midbrain dorsal raphe nuclei attenuate both morphine-produced and stimulation-produced analgesia. In contrast, norepinephrine depletion enhances both types of analgesia. To extend these findings, the effects of destruction of the noradrenergic locus coeruleus (LC) upon nociceptive flinch-jump thresholds were investigated. after four preoperative baseline sessions, lesions were placed in the LC bilaterally and nociceptive thresholds were determined for up to five weeks postoperatively. The lesions were localized by monoamine histofluorescence procedures together with conventional histological staining techniques. In 9 of 13 animals, the LC or its ascending dorsal noradrenergic bundle sustained either bilateral or unilateral damage, evidenced by green fluorescent back-up caudal to the lesions. Eight of these animals demonstrated significantly increased jump thresholds. In the remaining four animals, both lesions spared the LC and nociceptive thresholds were either unchanged or significantly decreased. In three of the four, raphe damage was noted, evidenced by yellow fluorescent back-up. The results suggest apparently contrasting roles of norepinephrine and serotonin in nociception.
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PMID:Elevations in nociceptive thresholds following locus coeruleus lesions. 64 13

The hypothesis that morphine acts on the serotonergic system to produce analgesia is based on the previous observations that (1) lesions and stimulation of midbrain raphe nuclei after the threshold to nociceptive stimuli; (2) morphine alters the turnover of serotonin (5-hydroxytryptamine; 5-HT). Microiontophoretic experiments were carried out to determine if morphine affected the firing rate of cells in five areas of the serotonergic system consisting of 5-HT containing neurons in the midbrain raphe nuclei (dorsal raphe and median raphe) or neurons in three areas (amygdala, optic tectum and subiculum) which are thought to receive a 5-HT input from the raphe nuclei. Morphine administered microiontophoretically slowed or inhibited the spontaneous neuronal firing in 34% of the cells studied in both the pre- and post-synaptic areas; systemically administered morphine gave similar results. However, the inhibition of neuronal firing by morphine in the five areas of the serotonergic system studied was not a specific narcotic effect because (1) it was not stereospecific; and (2) it was rarely blocked by naloxone. The inhibitory effect of morphine does not appear to be related to the analgesic effects of morphine because neuronal firing in the midbrain raphe nuclei and three possible postsynaptic areas was rarely altered by a nociceptive stimulus. It is concluded that (1) the analgesic effect of morphine is not related to an effect on neurons in the midbrain raphe nuclei and three areas which receive an identified 5-HT input; and (2) the effect of morphine on neurons in these five areas of the serotonergic system is not a specific narcotic effect.
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PMID:Morphine: effects on serotonergic neurons and neurons in areas with a serotonergic input. 71 May 10

Electrolytic raphe lesion was performed in 4-6-day-old rats and the resulting changes of 5HT metabolism within the central nervous system were analyzed up to 9 months later. As soon as the 2nd day following the selective destruction of B7 and B8 nuclei, forebrain 5HT levels were decreased by more than 75%. This reduction persisted for at least 9 months with no sign of recovery. The time course of 5-HIAA decrease was parallel to that of the indoleamine so that the ratio of 5-HIAA over 5-HT levels in the forebrain of lesioned rats was similar to that estimated in controls, whatever their age. This result would suggest that the remaining serotoninergic neurons in the lesioned rats did not develop a compensatory hyperactivity. The raphe lesion induced no change in MAO activity and synaptosomal tryptophan uptake but a pronounce decrease in the Vmax of synaptosomal KHT uptake process in various forebrain areas occurred. The serotonin sensitive adenylate cyclase activity in colliculi homogenate was not altered by the lesion suggesting that this enzyme was probably located in postsynaptic membranes. In addition, this observation would indicate that 5-HT receptors which are linked to this adenylate cyclase did not become supersensitive following the selective degeneration of serotoninergic neurons. Animals without forebrain serotoninergic innervation might be of great interest to analyse the role of serotoninergic neurons in various functions (sleep, analgesia, thermoregulation).
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PMID:Midbrain raphe lesion in the newborn rat: II. Biochemical alterations in serotoninergic innervation. 86 45

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


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