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

The effects of the alpha-adrenoceptor antagonists prazosin, phentolamine and yohimbine upon 5-methoxy-N,N-dimethyltryptamine (5-MeODMT)-induced analgesia were tested in the hot-plate, tail-flick and shock-titration tests of nociception with rats. Intrathecally injected yohimbine and phentolamine blocked or attenuated the analgesia produced by systemic administration of 5-MeODMT in all three nociceptive tests. Intrathecally administered prazosin attenuated the analgesic effects of 5-MeODMT in the hot-plate and tail-flick tests, but not in the shock titration test. Intrathecal yohimbine showed a dose-related lowering of pain thresholds in saline and 5-MeODMT-treated animals. Phentolamine and prazosin produced normal dose-related curves in the hot-plate test and biphasic effects in the shock titration and tail-flick tests. These results demonstrate a functional interaction between alpha 2-adrenoceptors and 5-HT agonist-induced analgesia at a spinal level in rats.
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PMID:5-Methoxy-N,N-dimethyltryptamine-induced analgesia is blocked by alpha-adrenoceptor antagonists in rats. 287 97

The antinociceptive role of spinal serotonin (5-HT) neurons descending from 5-HT cells near the ventrolateral surface of the medulla oblongata was investigated by stimulating these cells in normal rats, in rats with generalized or selective chemical ablation of 5-HT nerves, and in rats with postsynaptic blockade of 5-HT receptors. Electrical stimulation of the lateral medulla elicited analgesia in normal rats; the increase in pain threshold was proportional to the intensity and to the frequency of stimulation. In addition, microinjection of kainic acid or L-glutamate at the same sites also produced analgesia. However, generalized destruction of CNS 5-HT nerves produced by intraventricular injection of 5,7-dihydroxytryptamine (5,7-DHT) or selective destruction of spinal 5-HT nerves produced by intraspinal injection of 5,7-DHT reduced the magnitude of the antinociceptive responses to electrical stimulation. Postsynaptic blockade of CNS 5-HT receptors produced by intraventricular injection of cyproheptadine also reduced the stimulation-produced analgesia. The specificity of the lesions for 5-HT nerves is demonstrated by the lack of effect on the levels of noradrenaline in the same brain regions. The results indicate that the activity of 5-HT nerve cells adjacent to the ventrolateral surface of the medulla oblongata and projecting to the spinal cord serves to elevate pain threshold.
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PMID:The antinociceptive role of a bulbospinal serotonergic pathway in the rat brain. 289 26

Repeated administration of methylenedioxymethamphetamine (MDMA) to rats results in long-term depletion of serotonin (5-hydroxytryptamine; 5-HT) in several brain regions. Because of the apparent role of 5-HT in morphine-induced antinociception, the present experiment was designed to determine the effects of repeated MDMA injections on morphine-induced analgesia. Rats (n = 48) received 8 s.c. injections (one every 12 h for 4 days) of MDMA (20 mg/kg) or saline (1.0 ml/kg). Two weeks after the last injection, the groups were divided into 4 subgroups that received either saline, or morphine 2.5, 3.55 or 5.0 mg/kg (s.c.). Nociception was assayed before and after saline or morphine administration by the method of tail immersion in warm water (55 degrees C). The day after analgesia testing, the animals were sacrificed, brains and spinal cords removed and 5-HT, norepinephrine (NE) and dopamine (DA) levels in various brain and spinal cord regions were assayed. The analgesic effect of morphine was enhanced in rats that had received repeated MDMA injections. MDMA selectively depleted 5-HT in the cortex, hippocampus, striatum, brainstem and in the cervical portion of spinal cord. However, 5-HT levels were not changed in the thoracic and lumbar segments of the spinal cord. Thus, a functional consequence of repeated MDMA administration in rats was to enhance morphine-induced antinociception in association with reductions in brain and cervical spinal cord 5-HT.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Enhancement of morphine-induced analgesia after repeated injections of methylenedioxymethamphetamine. 290 95

The neurobehavioral responsiveness of two strains of rats, Fischer-344 (CDF) and Sprague-Dawley (CD), to a repeated foot-shock-induced analgesia (FSIA) stress was compared in this study. Rats were either restrained or freely moving during shock presentation (sham controls were exposed to the shock environment only). The foot-shock (15-s, 1.5-mA scrambled electric shock) was observed to induce analgesia in the CDF, but not the CD strain following acute presentation; analgesia was evaluated using time for tail-withdrawal from hot water (55 degrees C). Both strains exhibited an analgesic response when latency to tail withdrawal was evaluated just prior to daily FSIA presentations over 15 total sessions indicating that these rat strains were behaviorally conditioned to this repeated stressor. However, the levels of conditioned analgesic responses to foot-shock were: greater in the CDF and most evident when rats were restrained on the shock-grid while being administered the foot-shock. All rats were quickly sacrificed following the 15th conditioning session to determine the effects of this stressor on neurotransmitter and neuroendocrine function in both strains of rat. Experimental subjects were exposed to the shock grid but not shocked during this last session. The following was found: plasma corticosterone (CORT) and prolactin levels and adrenal CORT levels were significantly increased by repeated stress in the CDF strain; only plasma CORT levels were elevated in the CD rat; pituitary immunoreactive beta-endorphin levels were significantly higher (+46%) amongst all experimental groups in the CDF strain, but stress was not observed to alter peptide steady-state levels in either strain; dopamine (DA), 5-hydroxytryptamine and metabolites (5-hydroxyindoleacetic acid and dihydroxyphenylacetic acid) levels were generally higher in the hypothalamus and frontal cortex of the CDF rat but turnover rates (implied from metabolite/amine ratios) indicated that these systems were more sluggish in this rat strain; hypothalamic DA turnover was significantly attenuated by repeated FSIA + restraint in both strains, but the dynamics of this effect appeared to be different between rat strains; and frontal cortex 5-HT turnover was significantly elevated by repeated FSIA + restraint in only the CDF rat. This research indicates that the CDF rat is extremely sensitive to an acute FSIA stress and it is less able than the CD rat to adapt to repeated presentation of this stress.
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PMID:Neuroendocrine, biogenic amine and behavioral responsiveness to a repeated foot-shock-induced analgesia (FSIA) stressor in Sprague-Dawley (CD) and Fischer-344 (CDF) rats. 294 19

In experiments with both rats and mice the 5-HT agonists 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) and 5-methoxy-N,N-dimethyl-tryptamine (5-MeODMT) were shown to produce reliable analgesic effects after acute administration (1 mg/kg SC) in the tail-flick, hot-plate and shock-titration tests of nociception. Prior treatment with the noradrenaline neurotoxin, N-2-chloroethyl-N-ethyl-2-bromobenzylamine (DSP4), systemically administered to both rats and mice abolished the analgesic effects of both the 5-HT agonist compounds in all the tests of nociception used. Intrathecal 6-hydroxydopamine (6-OHDA) treatment also abolished the analgesic effects of 8-OH-DPAT and 5-MeODMT; in the tail-flick test the analgesia induced by 8-OH-DPAT was reversed to an hyperalgesia. Biochemical analyses confirmed notable noradrenaline depletions in the spinal cord. It is concluded that an important interaction between presynaptic noradrenergic terminals and serotonergic receptor sites, possibly 5-HT1A, mediates spinal nociception processes.
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PMID:(+)-8-OH-DPAT and 5-MeODMT induced analgesia is antagonised by noradrenaline depletion. 295 56

The effects of selective lesions of the descending serotonergic (5-HT) pathways on analgesia and avoidance deficit induced by the 5-HT releasing compound p-chloroamphetamine (PCA, 2.5 mg/kg) were investigated in male rats. Intrathecal injection of 5,6-DHT (20 micrograms/rat) reduced the uptake of labelled 5-HT into spinal synaptosomes by approximately 85% but did not significantly affect the uptake of noradrenaline. The lesions produced a significant hyperalgesia and strongly attenuated the analgesic effect of PCA in the hot-plate test. In the flinch-jump test 5,6-DHT lesioned rats receiving PCA did not differ from the saline control group. Spinal lesioning did not, however, affect one-way active avoidance performance and did not prevent the marked impairment of avoidance performance induced by PCA. Thus, the avoidance deficit caused by PCA is independent of the descending serotonergic pathways and of the analgesia induced by PCA. These results support the view of a differential involvement of the ascending and descending serotonergic projections in behavioural processes controlled by aversive stimuli.
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PMID:Involvement of spinal serotonergic pathways in nociception but not in avoidance learning. 300 2

The effects of changes in central serotoninergic transmission on clonidine analgesia were assessed in monkeys. The minimum electrical current required for producing jaw opening is referred to as the pain threshold. Pain was induced by electrical stimulation of tooth pulp afferents. In the first series of studies, intracerebroventricular administration of clonidine (5-30 micrograms) produced dose-dependent analgesia in monkeys. The clonidine-induced analgesia was abolished or attenuated by prior injection of the animals with p-chlorophenylalanine or 5,7-dihydroxytryptamine into the third cerebral ventricle. On the other hand, pretreatment of the animals by injecting 5-HT or its precursor 5-hydroxytryptophan into the cerebral ventricle potentiated the clonidine-induced analgesia in monkeys. In the second series of experiments, administration of clonidine (1-10 micrograms) into the diencephalic periventricular gray (of the anterior hypothalamic portion), the periaqueductal gray, or the dorsal raphe nuclei also produced dose-dependent analgesia in monkeys. The analgesia induced by clonidine injection into the diencephalic periventricular gray or the periaqueductal gray was effectively antagonized by pretreatment of the animals by injecting two 5-HT receptor antagonists (such as ketanserine and methysergide) into the diencephalic periventricular gray or the periaqueductal gray. The clonidine-induced analgesia in monkeys was not affected by pretreatment of the animals with injections of either ketanserine or methysergide into the dorsal raphe nuclei. The results suggest that the functional activity of central 5-HT neurons correlate well with the analgesic sensitivity of clonidine microinjected centrally. In addition, the analgesia induced by clonidine microinjected into the diencephalic periventricular gray or the periaqueductal gray was mediated by the 5-HT receptors at the site of injection.
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PMID:Changes in central serotoninergic transmission affect clonidine analgesia in monkeys. 303 80

The involvement of brain monoamines in the mechanism of action of nefopam, a new analgesic, was investigated in rats. The study was designed to evaluate the effect of various means of impairing monoaminergic transmission on nefopam analgesia as measured with the hot plate method. Pretreatment with reserpine (2 mg/kg) significantly reduced the antinociceptive action of nefopam (40 mg/kg), indicating that the interaction of this drug with the monoaminergic systems is important for its effects. A role for serotonin (5-HT) or norepinephrine (NE) was ruled out by the fact that selective depletion of 5-HT (using 5,7-dihydroxytryptamine) or NE (using DSP-4 or FLA-63) did not affect nefopam analgesia. A significant reduction of the effect of nefopam was found in rats pretreated with 6-hydroxydopamine (6-OHDA). Also 6-OHDA plus desipramine, which selectively depleted brain DA, markedly reduced the antinociceptive effect of nefopam. The data strongly suggest that a critical dopaminergic synapse is involved in the mechanism by which nefopam inhibits nociceptive responses in rats.
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PMID:Evidence of the involvement of dopamine in the analgesic effect of nefopam. 309 70

The acute effects of the 5-hydroxytryptamine agonist, 5-Methoxy-N,N-dimethyltryptamine (5-MeO-DMT), upon pain sensitivity, using shock titration, tail-flick and hot-plate methods, in noradrenaline- and 5-hydroxytryptamine-depleted rats were examined. Noradrenaline depletion, following the systemic administration of N-2-chloroethyl-N-ethyl-2-bromobenzylamine hydrochloride (DSP4, 2 X 50 mg/kg, i.p.), caused a reversal of the analgesic effect of 5-MeO-DMT on shock-titration from hypo- to hypersensitivity, and a total blockade of the antinociceptive effect of 5-MeO-DMT upon pain responses in the hot-plate and tail-flick tests. Pretreatment with either p-chloroamphetamine (2 X 10 mg/kg) or p-chlorophenylalanine (200, 100, 100 mg/kg), that depletes central 5-hydroxytryptamine stores, failed to alter the analgesia caused by acute 5-MeO-DMT. Strong evidence is provided for the effect of central noradrenaline depletion upon the analgesic effect of the 5-HT agonist. These findings suggest an important tonic influence of the noradrenaline system upon the descending spinal 5-HT pathway in rats.
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PMID:Blockade and reversal of 5-methoxy-N,N-dimethyltryptamine-induced analgesia following noradrenaline depletion. 315 73

Serotonin can induce analgesia when injected directly into the brain, but analgesia after peripheral administration has been more difficult to show. The pentobarbital anesthetized mouse (PAM) model, developed to alleviate some of the problems involved in the measurement of tail flick latency, was used to assess the action of peripherally administered serotonin. Mice were anesthetized with about 65 mg/kg of sodium pentobarbital IP and their tail flick latencies measured while they were in stage III anesthesia. In these anesthetized mice, IP serotonin induced a significant analgesia that was much more robust than that found in awake mice. The analgesic effect was dose-dependent from 0.25 mg/kg to 10 mg/kg but was not blocked by the antiopiate naltrexone. Of several psychotropic agents tested, only amitriptyline, mianserin, and trazodone had significant effects on analgesia in the PAM model. The analgesic effect of serotonin was reproduced by the 5HT2 agonist DOI and totally blocked by the 5HT2 antagonist NPP. These results show the utility of the PAM model in studying nonopiate analgesia and suggest that the analgesic action of serotonin is mediated primarily through the 5HT2 receptor.
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PMID:Mediation of serotonin-induced analgesia by the 5HT2 receptor in the pentobarbital anesthetized mouse model. 322 81


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