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)

Conjugate of horseradish peroxidase and wheat germ agglutinin (HRP-WGA conjugate) was injected into the midbrain central gray (MCG) of three adult rats. Frontal sections of the diencephalon were first treated with diaminobenzidine and hydrogen peroxide to detect the retrogradely transported conjugate. They were then stained immunohistochemically to detect pro-opiomelanocortin (POMC)-derived peptides (ACTH, beta-endorphin and alpha-MSH). The coexistence of the three POMC-derived peptides was confirmed by the immunohistochemistry of three consecutive sections stained with antiserum specific to each peptide. Some of the neuronal perikarya distributed in and around the arcuate nucleus were positive to the immunohistochemical stain for POMC-derived peptides, and, concomitantly, were labeled with HRP-WGA conjugate, which indicated that they projected to the MCG. They were mostly concentrated in the rostral three-fifths of the arcuate nucleus. The finding that some of the POMC neurons in the arcuate nucleus project to the midbrain central gray deserves interest, because the central gray is involved in analgesia induced by opioid peptides.
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PMID:Projection of pro-opiomelanocortin neurons from the rat arcuate nucleus to the midbrain central gray as demonstrated by double staining with retrograde labeling and immunohistochemistry. 245 87

Cerebrovascular dilation over PaO2 ranging from hyperoxia to moderate hypoxia is unexplained. We hypothesize that tissue acidosis is the cause. Local cortical cerebral blood flow (LCBF), tissue hydrogen ion concentration [H+]t, and tissue PO2 (PtO2) were measured with microelectrodes in the parietal cortex of 18 rats during a 30-min steady state on 60 to 10% inspired O2 (PaO2, 300 to 40 torr) during 40% N2O analgesia. Five rats kept on 60% O2/40% N2O served as controls. In 18 rats at a PaO2 of 275 +/- 7 torr (mean +/- SEM) and PaCO2 of 35 +/- 1 torr, cerebral values were: LCBF = 129 +/- 23 (mean +/- SEM) ml.100 g-1.min-1; [H+]t = 62 +/- 6 nM; and PtO2 = 25 +/- 3 torr. As PaO2 was reduced from about 300 to 40 torr, changes in these variables in percentage of control with respect to PaO2, were described by the following equations, all at P less than 0.0001: LCBF = 85.9 + 5,572/Pao2; [H+]t = 97.15 + 1,012/PaO2; and PtO2 = 108.8 - 3,492/PaO2. Simultaneous solution of the LCBF and [H+]t equations at various PaO2 revealed a slope of 8.82%/nM. Direct correlation between LCBF in ml.100 g-1.min-1 and [H+]t in nM revealed a linear relationship defined by the equation Y = -7.472 + 1.6705X (r = 0.6426) for [H+]t between 56 and 160 nM (pH = 7.25 and 6.80) but no correlation at [H+]t values between 56 and 32 nM (pH = 7.25 to 7.50). Cerebrovascular tone is directly correlated with [H+]t during progressive, 30-min steady-state reduction in PaO2 from 350 to 40 torr.
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PMID:Mechanisms of cerebrovascular O2 sensitivity from hyperoxia to moderate hypoxia in the rat. 292 Dec 94

The influence of a painful stimulus and lumbar epidural morphine on gastric emptying, the orocecal transit time and small intestinal transit were studied in nine healthy volunteers. Acetaminophen absorption was used as a measure of the rate of gastric emptying. Orocecal transit time was determined by measuring the end-expiratory hydrogen concentration. Small intestinal transit was calculated from measurements of the orocecal transit time and gastric emptying. Cold pain stress with intermittent immersion of the feet in ice-cold water was used as a painful stimulus. Each volunteer was investigated on 3 different days: once after receiving 4 mg of epidural morphine and during cold pain; once during cold pain; and once under control conditions without pain and epidural morphine. Immersion of the feet in ice-cold water was always very painful, but was more tolerable during epidural morphine analgesia. The increase in blood pressure which accompanied the cold pain was the same whether this pain was induced without or during epidural morphine analgesia. Gastric emptying, orocecal transit time and small intestinal transit were delayed during epidural morphine analgesia compared with the findings under the control and plain cold pain conditions. Cold pain stress alone did not influence gastric emptying, orocecal transit time or intestinal transit. To conclude, epidural morphine in itself delayed gastric emptying, orocecal transit and transit through the small intestine in healthy volunteers.
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PMID:Epidural morphine delays gastric emptying and small intestinal transit in volunteers. 292 84

Carbonated local anesthetics are less acidic than the hydrochlorides and require less buffering by the tissues. Rapid buffering and diffusion of the carbon dioxide enables free base to be deposited in high concentrations on nerve fibres. Carbon dioxide increases the intracellular hydrogen ion concentration, thus increasing the amount of active cation at the receptor site. The interscalene approach to the brachial plexus was chosen for comparison of bupivacaine hydrochloride 0.5% and carbonated bupivacaine 0.5%. The interscalene route has many potential advantages, including anesthesia of the shoulder and reliable block of the musculocutaneous nerve, but large volumes of local anesthetic solutions are needed. The use of such volumes may exceed the limit of toxicity. Therefore, the plasma concentrations produced by 40 ml of local anesthetic solution were studied in 42 patients for whom brachial plexus block was considered a suitable technique. The latency of onset of sensory analgesia was shortest and with the least variability in the dermatomes C5-C7. The first analgesia was detected by pinprick 5.1 +/- 0.4 (SE) min and complete analgesia in 19 +/- 1 min after bupivacaine hydrochloride and 4.7 +/- 0.5 min and 15 +/- 1 min after bupivacaine carbonate. The more caudad nerves showed a significantly longer latency time than the more cephalad ones. The duration of sensory analgesia varied between 6 and 12 hours, the more caudad nerves showing the shortest duration.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Comparison of bupivacaine hydrochloride 0.5% and bupivacaine carbonate 0.5% in interscalene plexus anesthesia]. 335 24

The delta Phe4-enkephalins have been synthesized and examined in an in vitro receptor binding assay and an in vivo tail flick analgesia test. The delta Phe4 residue was derived from Boc-Gly-Phe(beta-OH)-OH by spontaneous dehydration and azlactonization. The dipeptide azlactone was coupled directly with H-Leu-OBzl to yield a tripeptide which was converted into the pentapeptides after stepwise coupling with two amino acids using the water soluble EDC-HOBt method. Dehydroenkephalins were liberated with hydrogen fluoride in the presence of anisole. In the radioligand binding assay which did not contain an enzyme inhibitor [D-Ala2, delta Phe4, Leu5] enkephalin was almost twice as active as saturated [D-Ala2, D-Leu5]-enkephalin. The delta Phe4-enkephalins exhibited a considerably diminished activity as compared with the saturated peptide in the in vivo analgesic assay. These results are discussed with regard to the enzyme stability and receptor preference of dehydroenkephalins.
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PMID:Synthesis and biological activity of delta Phe4-enkephalins. 631 82

Narcotic agonists such as morphine are well known to decrease cerebral blood flow and metabolism. To investigate a possible mechanism for this action of narcotics, cerebral blood flow (CBF) and spinal cord blood flow (SCBF) were simultaneously measured by the hydrogen clearance technique following intravenous or subarachnoid administration of morphine and subsequent naloxone in lightly anesthetized dogs. The effects of new opiate agonist + antagonists, cyclazocine and buprenorphine, alone or in a combination with naloxone on those CNS blood flow were also investigated. Morphine, 1 mg/kg iv, produced significant decreases in both CBF and SCBF (p less than 0.01), which were reversed by naloxone, 40 micrograms/kg. Naloxone per se did not produce any change in both. Cyclazocine, 50 micrograms/kg iv, also produced significant decreases in both CBF and SCBF (p less than 0.05), but the decreased CBF was not reversed by naloxone. Buprenorphine, 30 micrograms/kg, showed variable changes in both CBF and SCBF, resulted insignificant reduction. However, spinal subarachnoid administration of morphine, 0.2 mg, with which profound analgesia can be obtained in human adults, did not cause any changes in SCBF as well as CBF. These results suggest that narcotic analgesics affect SCBF similar to CBF and morphine decreases CNS blood flow via the activation of supraspinal opiate receptors.
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PMID:[Mechanism of morphine-induced suppression of central nervous system blood flow]. 668 68

By means of the coloured indicator transport test (phenol red 3% in calcium-hydrogen-phosphate), mucociliary function in nose and pharynx was studied in 50 patients who underwent general or ocular surgery and in 10 healthy adult subjects. Patients were anesthetized with halothane, enflurane, NLA, and epidural analgesia. At the end of surgery, mucociliary function was significantly depressed (p less than 0.001) after halothane or enflurane anesthesia, but not after NLA or epidural analgesia. Six hours following enflurane anesthesia we still found a significant depression (p less than 0.001) of mucociliary function. No difference between halothane or enflurane was noted.
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PMID:Mucociliary flow in the nose during general and epidural anesthesia. 684 56

The effects of a thoracic epidural analgesia with morphine or bupivacaine on gastroduodenal motility during the fasted state and after food intake were evaluated in healthy volunteers. Nine volunteers were studied on two occasions, separated by at least 2 weeks, and were randomly allocated to receive either epidural morphine or epidural bupivacaine at the T6-T7 level on each occasion. Gastroduodenal motility was measured by manometry. Acetaminophen absorption was used as an indirect measure of the rate of gastric emptying and orocecal transit time was determined by use of the hydrogen breath test after ingestion of raffinose. During the control measurements, before the epidural analgesia, there were no differences in gastroduodenal pressure activity between the morphine and bupivacaine groups. Compared to epidural bupivacaine, epidural morphine significantly changed the pressure activity with a higher number of contractions in the duodenum, both during the fasted state and after food intake. Retrograde pressure activity was seen in the duodenum after epidural morphine but not after epidural bupivacaine. There were no significant differences in the pressure activity in the stomach after epidural morphine compared to epidural bupivacaine. Gastric emptying was delayed and orocecal transit time prolonged after epidural morphine. This study in volunteers showed that epidural morphine, compared to epidural bupivacaine, significantly changed the gastroduodenal motility, both during the fasted state and after food intake.
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PMID:Effects of epidural morphine and epidural bupivacaine on gastroduodenal motility during the fasted state and after food intake. 772 77

Methylnaltrexone is a quaternary opioid antagonist with limited ability to cross the blood-brain barrier and the potential to antagonize the peripherally mediated effects of opioids. The effectiveness of methylnaltrexone in preventing morphine-induced changes in gastrointestinal motility and transit without affecting analgesia was evaluated in humans. Twelve healthy volunteers were given intravenous placebo, placebo plus 0.05 mg/kg morphine, or 0.45 mg/kg methylnaltrexone plus 0.05 mg/kg morphine. Oral-cecal transit time was assessed by the pulmonary hydrogen measurement technique, and analgesia was measured with use of the cold-pressor test. Morphine significantly increased oral-cecal transit time from 104.6 +/- 31.1 minutes (mean +/- SD) to 163.3 +/- 39.8 minutes (p < 0.01). Methylnaltrexone prevented 97% of morphine-induced increase in oral-cecal transit time (106.3 +/- 39.8 minutes; not significant compared with baseline; p < 0.01 compared with morphine alone). Methylnaltrexone did not affect the analgesic effect of morphine on both pain intensity and pain bothersomeness ratings. At a higher dose of morphine (0.1 mg/kg), our preliminary results indicated that 0.45 mg/kg methylnaltrexone also prevented the morphine-induced delay in oral-cecal transit time, with no effect on analgesia. Methylnaltrexone may be a useful adjunct to opioids for the relief of opioid-induced constipation.
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PMID:Methylnaltrexone prevents morphine-induced delay in oral-cecal transit time without affecting analgesia: a double-blind randomized placebo-controlled trial. 861 93

Previous studies of the structure-activity relationships (SAR) for binding of a series of AC-bicyclic cannabinoid structures to the cannabinoid receptors in rat brain (believed to comprise the CB1 subtype) demonstrated the importance of the A-ring aryl C-3 side chain and phenolic hydroxyl substituents, and elucidated the importance of a C-ring hydroxyalkyl substituent [Melvin et al. Mol. Pharmacol. 44, 1008-1015 (1993)]. The present investigation examines the SAR surrounding this region (D-ring) of the molecule that is not present in the structure of delta(9)-THC and other classical cannabinoid compounds. Both rigid fused ring benzo and cyclohexyl derivatives (creating the D-ring) retained binding affinity for the cannabinoid receptor. Extension of ketone or hydroxyl substituents from the C2 position of the D-ring resulted in a 3-fold increase in binding affinity over the unsubstituted structure. However, the fused ring structure is not critical for the interaction with the receptor in as much as opening the ring did not decrease the potency. Extension of the D-ring C-2 alcohol by one carbon in length resulted in a pair of structures, for which the greatest affinity for the CB1 receptor occurred for the hydroxymethyl group in the axial conformation [(+/-)-CP-55,244]. Upon resolution, the latter provided a pair of enantiomers: (-)-CP-55,244 was approximately 3-fold more potent than the racemic mixtures, and (+)-CP-55,244 failed to bind to the CB1 receptor with an IC50 below 1 mM. Opening of the D-ring of these structures resulted in a loss of binding affinity. This study demonstrates that the potency could be optimized in (-)-CP-55,244 for both binding to the CB1 receptor and the biological activity of analgesia. In addition, the rigid positioning of the hydroxypropyl moiety of CP-55,940 enforced by the decalin ring structure of CP-55,244 increased the enantioselectivity by greater than 100-fold. These data define the critical stereochemistry for a region of the nonclassical ACD-tricyclic cannabinoid structure that contributes a potential hydrogen bonding component to the ligand-receptor interaction mechanism. Inasmuch as this region of the molecule is not present on classical ABC-tricyclic cannabinoid compounds, these studies elucidate a unique agonist recognition site on the CB1 receptor.
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PMID:Structure-activity relationships defining the ACD-tricyclic cannabinoids: cannabinoid receptor binding and analgesic activity. 887 58


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