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Query: UMLS:C0030193 (pain)
 261,466 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

We have previously demonstrated that scratching was significantly increased in a rat model of polyarthritis and that this could be reversed by morphine and electrical stimulation of pain-modulating brain areas. We therefore proposed that scratching might represent a parameter of chronic pain. In this study, we examined the spontaneous behaviour of rats in a model of peripheral neuropathy induced by loosely tying 4 ligatures around the right common sciatic nerve. In half of the animals (N = 7), the ligatures were made with resorbable sutures and, in the other half (N = 7), with non-resorbable sutures of the same size. Postoperatively, scratching was significantly increased at the ligated side. This increase was already observed on the first postoperative day, and maximal effects were reached on the 3rd day. We also observed a qualitative change in the scratching behaviour; postoperatively, scratching was often a vibratory-like shaking of the hind paw in the air. The time course of the increased scratching was time-locked with the development of allodynia to thermal stimulation. No differences were found either in the time course of the increased scratching behaviour or in the time course of the thermal allodynia between the rats ligated with resorbable and with non-resorbable sutures. However, a difference in the walking pattern, as measured by the sciatic functional index (SFI), was observed between the two groups: whereas the SFI normalized after 4 weeks in rats ligated with resorbable sutures, it remained disturbed until the end of the 16-week observation period in the rats ligated with non-resorbable sutures. Morphine 1, 2 and 5 mg/kg dose-dependently reduced the increased scratching behaviour. This was not due to a general depressant effect on the rats' behaviour. This finding is discussed in light of the debate on opioid sensitivity of neuropathic pain. The present results add new evidence that scratching is a possible sign of chronic pain in the animal.
Pain 1992 Jul
PMID:A time course analysis of the changes in spontaneous and evoked behaviour in a rat model of neuropathic pain. 132 48

Etorphine, a potent opioid agonist, has been reported to bind to both mu and epsilon opioid receptors. The present studies were designed to determine what types of opioid receptors and neurotransmitters for descending pain control systems were involved in antinociception induced by etorphine in mice. Morphine, a typical mu opioid receptor agonist, and beta-endorphin, an epsilon opioid receptor agonist, were used for comparison. Antinociceptive response induced by etorphine (20 ng) given i.c.v was blocked by i.c.v administration of D-Phe-Cys-Tyr-D-Tyr-Orn-Thr-Pen-Thr-NH2 (CTOP, 25 ng) and beta-endorphin-(1-27) [beta-EP-(1-27)] (6 micrograms), but not ICI 174,864 (ICI, 5 micrograms) or norbinaltorphimine (N-BNI, 5 micrograms). The antinociception induced by i.c.v. etorphine was also antagonized by the i.c.v. pretreatment of beta-funaltrexamine (beta-FNA, 50 ng, 24 hr). Intracerebroventricular administration of beta-EP-(1-27) (3 micrograms) caused a further attenuation of the i.c.v. etorphine-induced antinociception in mice pretreated with beta-FNA. The antinociceptive response induced by morphine (2 micrograms) given i.c.v. was blocked by i.c.v. administration of CTOP (25 ng) or beta-FNA (50 ng), but not beta-EP-(1-27) (6 micrograms), ICI (5 micrograms) or N-BNI (5 micrograms). These results indicate that the antinociception induced by etorphine given i.c.v. is mediated by the stimulation of both mu and epsilon opioid receptors whereas the antinociception induced by morphine given i.c.v. is mediated by the stimulation of mu, but not epsilon opioid receptors at supraspinal sites.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Involvement of supraspinal epsilon and mu opioid receptors in inhibition of the tail-flick response induced by etorphine in the mouse. 132 9

Morphine or naloxone injected twice a day (10 mg/kg/day) to rat females from 15 to 18 days of gestation had no effect on their litter size or body weight of pups. Time necessary for the female to bring pups into the nest from the opposite end of the cage, that is a characteristic of maternal care and negatively correlated with the mean body weight of the pup in the litter, did not change after treatment with drugs during gestation. Newborns treated with mu-opioid receptor ligands during intrauterine development had an elevated number of 3H-naloxone binding sites in the brain. However, the number of 3H-naloxone binding sites on the 9 and 16 days of life, as well as pain thresholds under electric stimulation of the tail at a month age were equal in these rats and offsprings of the intact or saline treated mothers.
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PMID:[Maternal behavior after the administration of morphine or naloxone to pregnant female rats and the pain sensitivity and brain mu-opioid receptors in the progeny]. 132 83

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

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 main aim of sedation in the critically ill patient is to provide relief from anxiety and pain. The current, ideal level of sedation should leave a patient who is lightly asleep but easily roused. No single regimen is suitable for all patients. The level of sedation should be monitored, and the choice of agent, the dose and the route of administration adjusted appropriately. Midazolam is often used to provide sleep and anxiolysis. Alternatives include propofol and isoflurane. Propofol is easily titrated to achieve the desired level of sedation, and its effects rapidly end when the infusion is stopped. Isoflurane also appears promising, but special equipment is needed for its administration. Morphine is the standard analgesic agent. The principal metabolites, morphine-6-glucuronide, is also a potent opioid agonist and may accumulate in renal failure. Of the newer analgesic agents, alfentanil is an ideal agent for infusion, and may be the agent of choice in renal failure. Neuromuscular blocking agents are indicated only in specific circumstances, and used only once it is known patients are asleep and pain free. The actions of these agents are unpredictable in the critically ill patient. Alterations in drug effect and elimination may occur, especially in the patient with hepatic and renal failure. This may also apply to active metabolites of the parent drug. When planning sedation regimens, specific patient needs and staffing levels must be remembered. Attention to the environment is also important. Midazolam and morphine given by intermittent bolus or by infusion are the mainstay of most regimens. Propofol is ideal for short periods of care on the ICU, and during weaning when longer acting agents are being eliminated.
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PMID:The use of sedative agents in critically ill patients. 137 17

Atrial natriuretic peptide (ANP) is known to participate in different vegetative functions. The aim of the present study was to investigate the influence of ANP on nociception itself, pain sensitivity to morphine, and the development of acute and chronic tolerance to morphine. Morphine withdrawal signs were also evaluated by injecting naloxone. In adult, male NMRI mice, ANP administered SC or ICV did not affect pain sensitivity itself in a heat-radiant tail-flick test. Peptide treatment, however, depressed the acute nociceptive effect of a single dose of morphine (4 mg/kg, SC) after both SC (20-200 ng/animal) and ICV (5, 10, 20, or 200 ng/animal) ANP administration. ANP given SC and ICV attenuated the development of acute morphine tolerance. Acute morphine tolerance was assessed by giving a bolus injection of morphine (60 mg/kg) 24 h before the pain sensitivity to a challenge dose of morphine (4 mg/kg) was measured. ICV treatment with ANP also blocked the development of chronic morphine tolerance, but did not affect the appearance of naloxone-precipitated withdrawal syndromes. ANP seems to act differently on the development of tolerance to and dependence upon morphine.
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PMID:Effects of atrial natriuretic peptide on acute and chronic effects of morphine. 140 4

The effects of depletion of the serotonin precursor, L-tryptophan, on the threshold and tolerance to cold pressor pain, and the analgesic effect of morphine (10 mg intramuscularly), were tested in a double blind trial on human volunteers. Effects on mood were also assessed using the Profile of Mood States and the Addiction Research Center Inventory (ARCI) Scales. To deplete tryptophan, subjects were fed a tryptophan-deficient amino acid mixture 4.5 h before morphine was administered. Controls received the mixture with tryptophan, which is equivalent to a nutritionally balanced protein. The tryptophan-deficient meal reduced plasma tryptophan more than 70% but had no effect on threshold or tolerance to cold pressor pain. After morphine, tolerance to cold pressor pain increased in controls. Tryptophan depletion abolished this analgesic effect. Pain threshold was not altered by morphine. In subjects with normal tryptophan, the analgesic effect of morphine was predicted by the level of plasma morphine-6-glucuronide, but not by the level of morphine. Morphine increased scores on the LSD scale of the ARCI, but had no effect on other measures of mood. Tryptophan depletion also failed to alter mood in these subjects, who had unusually low depression scores before tryptophan depletion.
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PMID:Acute tryptophan depletion blocks morphine analgesia in the cold-pressor test in humans. 141 Jan 47

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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