Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0344307 (analgesia)
 28,200 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Identified neurons in the buccal ganglion of the marine mollusc Navanax inermis were used to examine the effects of acetanilides on neuronal membrane properties. Acetanilides increased the membrane potential and conductance of these neurons in a dose-dependent, reversible manner. These events would have the effect of decreasing membrane excitability. Acetanilides increased the slope of the curve of membrane potential as a function of log [K+]o from 33 to 58 mV decade change in [k+]o and decreased the transient depolarization observed upon reducing [Cl]o. These results indicate that acetanilides increase membrane potential and conductance by increasing the potassium conductance of the membrane relative to the chloride conductance. The variation in membrane potential as a function of external alkali-cation concentrations was used an as indirect measure of alkali-cation permeability. Acetanilides altered the relative cation permeability from Rb (1.25) greater than K (1.0) greater than Cs (0.60) greater than NaequalsLi (0.07) to K (1.0) greater than Rb (0.71) greater than Cs (0.31) greater than NaequalsLi (0.00). This shift in relative cation permeability is interpreter, in terms of Eisenman's theory of membrane permselectivity, as indicating that acetanilides increase the anionic field strength of the membrane. The ability of acetanilides to increase membrane potential or alter permselectivity is directly correlated with octanol-water partition coefficient (r equals 0.96), indicating that hydrophobicity per se can account for almost all of the activity. Steric factors are unimportant. Analysis of published experiments on acetanilide analgesia in mice reveals that hydrophobicity can also account for much of the activity in that system. Results obtained in the molluscan system may thus provide insight into the ionic, biophysical and physicochemical mechanisms underlying acetanilide-induced analgesia.
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PMID:Acetanilides: effects on invertebrate neurons correlated with analgesic activity in vertebrates. 115 38

Treatment of rats with desipramine (DMI) 1 hour before the subcutaneous administration of methadone increased the intensity and prolonged the duration of methadone analgesia, as determined by the hot plate method. DMI significantly reduced the analgesic ED50 of methadone from a control value of 3.4 to 1.6 or 0.5 mg/kg in rats treated with 20 or 30 mg/kg of DMI, respectively. DMI treatment also significantly reduced the LD50 of methadone. DMI (20 mg/kg i.p.) was given 1 hour prior to administration of 14C-methadone (5 mg/kg s.c.) and the distribution of total 14C, unchanged methadone and methadone metabolites in various tissues was studied. DMI treatment greatly increased the brain uptake of 14C and the methadone brain/plasma concentration ratios for up to 3 hours. The concentrations of 14C and unchanged methadone were higher in kidneys and lower in lungs of DMI-treated rats as compared to controls. However, the ratios of unchanged methadone to its metabolites in kidneys and lungs were not changed significantly by DMI treatment. The level of unchanged methadone in liver was markedly elevated by DMI treatment at 45 and 90 minutes (190 and 183% of controls, respectively). The level of a water-soluble glucuronide metabolite of methadone was significantly decreased at 45-, 90- and 180-minute intervals (37, 36 and 54% of controls, respectively.) However, the total 14C in liver and the concentrations of two N-demethylated metabolites of methadone were not changed significantly. In vitro addition of DMI to liver microsomal incubations resulted in inhibition of the N-demethylation of methadone. It is suggested that DMI potentiated and prolonged methadone analgesia by increasing the brain concentration of methadone and by inhibiting metabolism of methadone in the liver.
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PMID:Increased analgesia and alterations in distribution and metabolism of methadone by desipramine in the rat. 118 9

Midazolam is a water-soluble benzodiazepine with low toxicity. It has anxiolytic and sedative effects. This study assessed the efficacy and tolerance of this drug for sedation in various ward procedures. Pethidine was added to bone marrow aspirations for analgesia. 57 children with the mean age of 48 months and mean weight of 15.7 kilograms were studied. The dose of midazolam used to sedate adequately 86% of the children was 0.73mg/kg, the average onset of sedation was 4.3 minutes and mean duration was about 88 minutes. 47.5% were completely sedated, whereas 38.5% were only partially sedated. In 14%, sedation was not achieved at all. There was a statistically significant drop in blood pressure after sedation but this was not associated with any clinical effects. Hypoventilation was not detected in this study.
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PMID:Use of intravenous midazolam for sedation in children undergoing ward procedures. 130 62

The endogenous opioid peptides are known to play a significant role in the modulation and/or mediation of numerous environmental or experimental stressors. However, the specific opioid peptide(s) and receptor type(s) involved, under what physiologic conditions they are engaged and within which regions of the CNS is not well understood. We therefore examined the effects of both a chronic and an acute stressor-90-h water deprivation and a single 20-min foot shock on opioid receptor binding in 17 specific rat brain nuclei. [3H]DSTLE (Tyr-D-Ser-Gly-Phe-Leu-Thr) and [3H]DAGO(Tyr-D-Gly-Phe-NMe-Phe-Gly-ol) were used to label delta and mu receptors, respectively. Foot shock induced profound antinociception as measured by tail-flick latency which outlasted the stressor by several minutes. However, only the septum responded with a decrease in [3H]DAGO binding to this type of stress-induced analgesia. No other alterations in either [3H]DAGO or [3H]DSTLE binding were seen in response to foot shock. In contrast, water deprivation induced increases in [3H-DAGO] binding in the septum as well as increases in [3H]DSTLE binding in the caudate and accumbens nuclei. Moreover, the presumptive mild stress of handling in the foot shock control group was sufficient to decrease mu or delta receptor binding in seven out of 17 brain regions investigated (including the frontal cortex and olfactory tubercle where both mu and delta binding were increased) when compared to unhandled deprivation control animals. These changes in opioid receptor binding may have been the result of alterations in treatment-induced peptide release, receptor regulation, or interactions with other released neurotransmitter ligand/receptor complexes.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of stress on opioid receptor binding in the rat central nervous system. 133 24

2-Hydroxypropyl-beta-cyclodextrin (CDEX), a seven-membered glucose pyranose structure, forms reversible inclusion complexes with the lipophilic portion of a drug molecule by noncovalent bonding. This can increase the water solubility of lipid-soluble drugs and reduce the rate of clearance of such agents from the spinal cord into the vasculature after i.t. administration. In this study, opioids (morphine, lofentanil, alfentanil and sufentanil) with and without CDEX (20, 2, 0.2 and 0.02% w/v in sterile water) were administered spinally in rats prepared with chronic i.t. catheters. CDEX prolonged the duration of analgesia (52.5 degrees C hot plate) and reduced the incidence of catalepsy otherwise produced by a supermaximal i.t. dose of each of the opioids. The magnitude of the potentiating effect of CDEX on opioids was dependent upon concentration of the CDEX and varied with drug lipid partition coefficients. The highest concentration of CDEX alone (20%) had no effect upon the volume-evoked micturition reflex, blood pressure, heart rate, or spinal reflexes. Our data indicate that CDEX may be a useful i.t. vehicle for modifying the redistribution characteristics of highly diffusible molecules after their i.t. administration, and that for each drug there is an optimal CDEX concentration. In the present case, CDEX prolongs the spinal analgesic action and reduces the supraspinal actions of i.t. drugs.
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PMID:Use of 2-hydroxypropyl-beta-cyclodextrin as an intrathecal drug vehicle with opioids. 134 42

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

The analgesic effect of a 3-min swim stress was assessed using the formalin test. Male Swiss mice were injected i.p. with naloxone (0.1 or 1.0 mg/kg), MK-801 (0.075 mg/kg) or saline 15 min prior to swimming in water maintained at 20 degrees C or 32 degrees C. The mice were then injected with 20 microliters of 5% formalin into the plantar surface of 1 hind paw and pain behaviour (time spent licking the injected paw) was continuously monitored during the subsequent 10 min. Swim stress produced a significant reduction in pain behaviour at both 20 degrees C and 32 degrees C. MK-801 completely blocked the analgesia produced by both the 20 degrees C and 32 degrees C swim. At a dose of 0.1 mg/kg, naloxone partially antagonized the analgesia produced by the 32 degrees C swim but did not affect the analgesia produced by the 20 degrees C swim. Naloxone at a dose of 1.0 mg/kg had no effect on swim stress-induced analgesia. Neither MK-801 nor 0.1 mg/kg naloxone altered baseline pain behaviour, although 1.0 mg/kg naloxone did significantly reduce it. It is unlikely that the effect of MK-801 on swim stress-induced analgesia is due to an interaction with an opioid mechanism, as MK-801 had no effect on morphine analgesia. These results suggest that the analgesia produced by the 20 degrees C swim stress in the formalin test is non-opioid in nature and mediated via the NMDA receptor, whereas the 32 degrees C swim stress-induced analgesia has both an opioid and non-opioid component.
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PMID:NMDA receptor antagonist MK-801 blocks non-opioid stress-induced analgesia in the formalin test. 138 68

Nitrous oxide analgesia was introduced into obstetrics by a young Polish-Russian physician who manufactured the gas himself, mixed it with oxygen, humidified the mixture with water vapor, and devised a mouthpiece for self-administration. After assessing the results on himself, he evaluated the effects on pain relief, maternal emotion, and maternal and fetal heart rates, as well as on the frequency, duration, and strength of uterine contractions in 25 parturients. He recognized that, in contrast to chloroform, nitrous oxide did not alter uterine activity. He concluded that the advantages of nitrous oxide administration far outweighed its disadvantages.
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PMID:The introduction of nitrous oxide analgesia into obstetrics. 140

A case is reported of a persisting leakage of cerebrospinal fluid (CSF) occurring after removal of a subarachnoid analgesia kit. The kit had been inserted in a 79-year-old man who had severe perineal cancer pain. Fifteen months later, after a second episode of meningitis, the kit was removed. The leakage was noticed a few hours after removal of the kit. Biological parameters confirmed the fluid was most certainly CSF. Despite making the patient lie prone, water restriction and a compressive dressing, the leakage was still present three days later. A blood patch, and the epidural injection of biological glue, were of no avail. The leakage was only stopped by tying off the fistula with a ligature. The actiology and treatment of skin CSF fistulae after puncture of the dura mater are discussed.
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PMID:[Persistent leakage of cerebrospinal fluid after removal of a device implanted for subarachnoid analgesia]. 141 83

A eutectic mixture of local anesthetics (EMLA) contains 2.5% lidocaine and 2.5% prilocaine in an oil and water emulsion and has been found to give effective, safe analgesia on normal and diseased skin, making it useful for numerous medical and surgical procedures, such as anesthesia for superficial surgery, split-thickness skin grafts, venipuncture, argon laser treatment, epilation, and debridement of infected ulcers. Other indications have included use in postherpetic neuralgia, hyperhidrosis, painful ulcers, and inhibition of itching and burning. To be effective, EMLA should ideally be applied to the desired area for at least 1 hour under an occlusive dressing. The medication has been approved since May 1991 in Canada for use on intact skin and has been available in Europe for many years. This study discusses the background, efficacy, and current and potential uses of EMLA.
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PMID:EMLA. A new and effective topical anesthetic. 815 Oct 42


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