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

The neural substrates of endogenous supraspinal opioid pain inhibition are mediated in part by connections between the midbrain periaqueductal gray (PAG) and the ventral-medial medulla, including the nucleus raphe magnus (NRM) and nucleus reticularis gigantocellularis (NRGC). To ascertain whether a serotonergic synapse participated in this pathway, the present study determined whether microinjections of methysergide into the NRM or NRGC would alter analgesia elicited by morphine microinjections into the PAG. Morphine (2.5 micrograms) in the PAG and immediately adjacent areas produced significant analgesia on the tail-flick and jump tests in rats. Pretreatment with the serotonin receptor antagonist methysergide (0.5-5 micrograms) in either the NRM or NRGC significantly reduced morphine analgesia elicited from the PAG by 69% on the tail-flick and by 50% on the jump tests without altering basal nociceptive thresholds. Medullary placements ventral or lateral to the NRM/NRGC failed to support this antagonistic effect. These data indicate that a ventro-medial medullary serotonergic synapse participates in the transmission of opioid pain-inhibitory signals from the PAG.
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PMID:Inhibition of mesencephalic morphine analgesia by methysergide in the medial ventral medulla of rats. 131 Nov 8

The role of endocrine factors on opioid analgesia (antinociception) and opioid receptors was studied in male and female Swiss-Webster mice. Morphine was more potent in male than in female mice, although this difference appears to be due to greater availability of morphine to the brain in males. Saturation binding studies indicated that the density and affinity of brain mu- and delta-opioid binding sites were equivalent in males and females. Males and females were implanted SC with naltrexone (NTX) or placebo pellets for 8 days, and then the pellets were removed. This treatment increased the density of mu and delta binding sites in brain and increased the potency of morphine for both sexes, although the increase in antinociceptive effects for males was greater than for females. Adrenalectomy (ADX) in male mice increased the potency of morphine and methadone but did not alter the brain levels of either drug. ADX did not alter brain opioid binding of either mu or delta ligands. When male ADX and control mice were treated with NTX, the potency of morphine and brain opioid binding sites were increased equivalently in both groups. Gonadectomy (GDX) in male mice tended to decrease morphine potency, although this was not found to be a very reliable effect. When male GDX and control mice were implanted with NTX, brain opioid binding was increased similarly in both groups, although morphine potency was increased less in GDX mice. Overall, these studies show that sex differences and hormones of the adrenals and gonads in male mice do not alter brain opioid receptors.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of adrenal and sex hormones on opioid analgesia and opioid receptor regulation. 132 57

We assessed the roles of brain monoaminergic systems in the analgesic action of spiradoline, a novel kappa-opioid agonist, behaviorally and biochemically by using noradrenaline (NE) and serotonin (5-HT) uptake inhibitors. Analgesic activity was evaluated by measuring latency time in the mouse tail-pinch test. Spiradoline at intramuscular doses of 0.3 mg/kg or more elicited a significant analgesic effect and the metabolism of both NE and 5-HT was significantly increased in brainstem and cortex. Pretreatment of the mice with imipramine, desipramine or clomipramine caused marked potentiation of spiradoline analgesia, whereas reserpine and phenoxybenzamine inhibited it. Morphine analgesia was enhanced by clomipramine but not by imipramine, desipramine or phenoxybenzamine. These results suggest that excitation of noradrenergic and serotonergic pathways in the brain appears to be involved in spiradoline analgesia, and that, as regards tail-pinch nociception, the kappa-opioid agonist acts on the noradrenergic pathway more potently than morphine.
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PMID:Central monoaminergic mechanisms in mice and analgesic activity of spiradoline mesylate, a selective kappa-opioid receptor agonist. 132 50

The mammalian pineal gland and its main hormone, melatonin, working in conjunction with the hypothalamic suprachiasmatic nuclei, synchronize circadian rhythm and hence refine numerous physiological and biochemical parameters. An interaction among melatonin, opioids, and analgesia has been suspected for many years, since during nighttime, when the level of melatonin is high, the mammals are less sensitive to pain. In studying this phenomenon further, we have identified a single population of opioid receptors in the bovine pineal gland using [3H]-diprenorphine and other ligands. The receptors have a dissociation equilibrium constant (Kd) of 1.36 +/- 0.31 nM and a density (Bmax) of 17.93 +/- 5.22 fmol/mg protein. In competitive experiments, the concentration of drugs required to inhibit 50% of the [3H]-diprenorphine binding (IC50) in descending order of potency was found to be naltrexone > fentanyl > naloxone > nalbuphine > morphine > nalorphine > DAGO > dynorphin > metenkephalin. In order to delineate the function of the opioid system in the pineal gland, the effects of both opioid receptor agonists and antagonists on the basal activity of N-acetyltransferase were examined in the bovine pineal explants in culture. Morphine, an opioid receptor agonist, increased significantly the activity of N-acetyltransferase in a dose-dependent fashion. In addition, the stimulatory effect of morphine was inhibited by naloxone, an opioid receptor antagonist. The results of these studies indicate the existence of pineal opioid receptors, which play a pivotal role in the synthesis of melatonin and its action in synchronizing pineal events.
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PMID:The presence and actions of opioid receptors in bovine pineal gland. 133 47

The aim of these experiments was to examine the changes in antinociception elicited by morphine or glutamate stimulation of the periaqueductal gray of the midbrain (PAG) during the postnatal development of the rat. Pups, aged 3, 10, and 14 days, were implanted with cannulas aimed at either the dorsal or the ventral aspect of the PAG, and glutamate (vehicle, 60 mM or 180 mM) or morphine (vehicle, 2 micrograms or 6 micrograms) was microinjected into one of those two sites. Pups were tested for analgesia against noxious thermal and mechanical stimuli. Morphine produced analgesia at 3 and 10 days of age only when administered to the ventral part of the PAG and the thermal noxious stimulus was tested. Conversely, analgesia induced by glutamate was seen at 3 and 10 days of age only when glutamate was given to the dorsal aspect of the PAG and the mechanical stimulus was used. In 14-day-old pups, both drugs produced analgesia against both types of noxious stimuli regardless of their site of administration within the PAG. Systemically administered naloxone attenuated the analgesic effects of both drugs when they were administered to the ventral PAG, but did not consistently attenuate the analgesic effect of either compound given to the dorsal aspect of the PAG. When either morphine or glutamate was injected into the ventral PAG, intrathecal injections of methysergide attenuated analgesia against the thermal stimulus to a significantly greater degree than the mechanical stimulus and intraspinal injection of phentolamine attenuated analgesia against the mechanical stimulus more potently. When glutamate was given to the dorsal PAG, analgesia against both stimulus types was significantly attenuated. These results indicate that the morphine- and glutamate-induced analgesia mediated by the PAG are developmentally differentiated. These ontogenetic differences most likely reflect differences in the mechanism of action by which these drugs produce analgesia when administered to the PAG, as well as neuroanatomical differences within the dorsal and the ventral regions of the PAG.
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PMID:Analgesia from the periaqueductal gray in the developing rat: focal injections of morphine or glutamate and effects of intrathecal injection of methysergide or phentolamine. 135 95

Effects of dietary proteins such as casein and egg albumin on analgesic activity of, tolerance to and physical dependence on morphine in rats were examined. There was no difference in analgesic activity after acute administration of morphine 10 mg/kg, s.c. between rats treated with casein food or egg albumin food and normal food for 5 or 21 days. The development of tolerance to morphine analgesia in rats treated with albumin food but not with casein food was suppressed during daily morphine 10 mg/kg, s.c. on 5 consecutive days. Rats were treated with casein or albumin food mixed with morphine (0.5 mg/g of food) for 5 days. Morphine intake in rats treated with albumin food was significantly decreased as compared to that with morphine admixed casein or normal food. Body weight loss by naloxone in morphine-dependent rats was significantly less in both casein food and albumin food groups than in the normal food group. These results suggest that chronic dietary treatment with albumin may produce a partial inhibition of development of tolerance to morphine analgesia and that with casein may attenuate morphine withdrawal manifestation in rats.
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PMID:[Effects of dietary proteins on analgesic activity of tolerance and physical dependence on morphine in rats]. 135 65

This prospective and comparative study was designed to determine the role of cancer pain and attitudes towards morphine in attenuating the intensity and duration of physical dependence following chronic morphine treatment. Morphine was administered via a stepwise ladder approach in order of oral, spinal and intravenous routes depending on the adequacy of analgesia. On-demand titration of a dose, either upward or downward, was liberal and unlimited. Withdrawal strategy was evaluated and initiated either by patients (PI group) or their families (FI group). The manifestation of physical dependence on morphine was compared between patients who successfully withdrew (total withdrawal), and patients who failed to withdraw (episodic withdrawal), from morphine for a period of more than two weeks. Eighty-eight out of 627 patients (14.1%) were excluded from our protocol; 75% of these exclusions were due to objections toward morphine as the major form of analgesic. Drop-out due to poorly tolerated side effects was relatively rare (18.2%). Fifty-four (10.0%) achieved total withdrawal and 212 (39.3%) experienced episodic withdrawal. Non-pain-related abstinence symptoms were highly prevalent but were tolerable for both groups. Pain-related symptoms were more exaggerated during episodic withdrawal. Intolerable pain, rather than physical dependence, contributed to the failure to withdraw from morphine. Among a total of 539, addiction was found in only one patient (0.18%) who began drug use long before entering our protocol. Attitudes towards morphine affect the acceptance of treatment and hasten the withdrawal strategy. Families were more anxious about morphine than the patients themselves which led to more aggressive, but less tolerable, withdrawal.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Can cancer pain attenuate the physical dependence on chronic long-term morphine treatment? 135 30

The analgesic response to 10 mg/kg of morphine hydrochloride, administered intraperitoneally, was examined in mice made diabetic by treatment with alloxan using the hot plate method. The hot plate base line latency of diabetic mice was significantly higher than that of normal mice. Morphine was found to possess an hyperglycaemic effect in both normal and diabetic mice. A decreased analgesic response to morphine was observed in diabetic mice. The decreased response seemed to be associated with plasma glucose levels, since multiple injections of insulin replacement abolished the decrease in morphine analgesia in diabetic mice. However, a single injection of insulin or glucose loading did not modify morphine analgesia. Naloxone was an effective antagonist of the analgesic and hyperglycaemic effects of morphine in both normal and diabetic mice, but induced a greater reduction of the plasma glucose level in diabetic than in normal mice. It is suggested that a supranormal dose of morphine may be needed in diabetics.
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PMID:Morphine analgesia in normal and alloxanized mice. 136 Nov 22

The effects of the specific N-methyl-D-aspartic acid (NMDA) receptor antagonist MK-801 (dizocilpine, 0.075 mg/kg, i.p.) on swim-stress-induced analgesia (SSIA) were studied in control (C) mice and in mice selectively bred for high (HA) or low (LA) SSIA. In three consecutive experiments, animals were subjected to forced swimming at water temperature of 20 degrees C, 32 degrees C and 15 degrees C and the resulting analgesia (hot-plate test) was found to be mixed opioid/non-opioid, opioid and non-opioid, respectively, as a function of the degree of antagonism by naloxone (10 mg/kg, i.p.). The major finding of this study is that MK-801 attenuated 15 degrees C SSIA, against which naloxone was ineffective, but had no effect on 32 degrees C SSIA, which naloxone blocked completely. A combination of naloxone and MK-801 significantly attenuated 20 degrees C SSIA in C and HA mice and in HA mice this attenuation was significantly larger than that produced by either drug alone. Morphine analgesia (10 mg/kg, i.p.) was unaffected by MK-801. It is concluded that low doses of MK-801 selectively block non-opioid mechanisms of SSIA.
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PMID:N-methyl-D-aspartic acid (NMDA) receptor antagonist MK-801 blocks non-opioid stress-induced analgesia. II. Comparison across three swim-stress paradigms in selectively bred mice. 138 34

Thirty cancer patients, clinical group IV, have been examined. It has been established that a persistent pain syndrome leads to lowering in beta-endorphin liquor level. Morphine analgesia is followed by beta-endorphin level elevation which directly depends on pain intensity and analgesia efficacy. Determination of changes in beta-endorphin liquor level may serve as a criterion of analgesia efficacy.
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PMID:[Changes in the concentration of beta-endorphin in the cerebrospinal fluid due to morphine analgesia in incurable oncologic patients]. 141 98


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