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)

The analgesic effects of i.c.v. morphine and the enzyme-resistant enkephalin analogs, D-Ala2-Leu- and D-Ala2-Met-enkephalinamide, measured in the tail-flick test, were compared in nondependent and morphine-dependent rats. Dependence was induced and maintained by scheduled access to 0.05% morphine solution for at least 8 weeks before testing. In the nondependent rats, 1.0 to 10 micrograms of each drug injected into the lateral ventricle produced a dose-related increase in analgesia; on a molar basis, morphine was 1.3 (1.0-1.7) times more potent than the enkephalins. Naloxone (0.3 and 1.0 mg/kg) antagonized the analgesic effect of the three compounds: the effect of morphine was competitively antagonized, whereas the interaction between naloxone and the enkephalins did not appear to be competitive. Chronic morphine treatment produced different changes in the analgesic effects of morphine and the enkephalins. In contrast to the tolerance that was observed after s.c. injection of morphine in morphine-dependent rats, the analgesic effect of i.c.v. morphine was enhanced in these animals. The analgesic effect of D-Ala2-Leu-enkephalinamide was also enhanced in morphine-dependent animals, whereas tolerance developed to the effect of D-Ala2-Met-enkephalinamide. Thus, the analgesic effect of morphine and enkephalins are differentially altered in the presence of naloxone and in morphine-dependent animals. These results could reflect an allosteric interaction between neuronal binding sites for enkephalins and opiate alkaloids.
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PMID:Analgesic effects of intraventricular morphine and enkephalins in nondependent and morphine-dependent rats. 720 Oct 20

Methionine- and leucine-enkephalin produce mild and transient analgesic effects, presumably because of enzymatic degradation. Administration of high (250 mg/kg) doses of D-phenylalanine retards the degradation process and elicits analgesia which is reversed by naloxone and which summates with electroacupuncture analgesia. The present study evaluated D-phenylalanine's dose-dependent effects upon a non-opioid analgesic treatment, cold-water swims (CWS), and compared this with morphine. following determination of flinch-jump baselines, three groups of rats received respectively either 25, 50 or 100 mg/kg of D-phenylalanine intraperitoneally in three conditions: alone, with CWS (2 degrees C for 3.5 min), and with morphine (5 mg/kg, SC). Parallel controls with saline were also tested. Simultaneous exposure with each minimally analgesic dose of D-phenylalanine reduced significantly the analgesic, but not hypothermic effects of CWS. By contrast, morphine analgesia was unaffected by D-phenylalanine. These data provide further support that different pain-inhibitory systems mediate CWS and morphine analgesia and suggest that activation of one system is capable of exerting collateral inhibition upon the other.
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PMID:Antagonism of stress-induced analgesia by D-phenylalanine, an anti-enkephalinase. 720 49

Effects of taurine or gamma-aminobutyric acid (GABA) on akinesia and analgesia induced by D-Ala2-Met-enkephalinamide were investigated in rats. Administration of taurine (dose range: 2.375 X 10(-2) M-9.5 X 10(-2)-Met-enkephalinamide were investigated in rats. Administration of taurine (dose range: 2.375 X 10(-2) M-9.5 X 10(-2) M/10 microliters) into the left lateral ventricle 10 min prior to the injection of D-Ala2-Met enkephalinamide (50 microgram/10 microliter) produced a dose-dependent reduction in the duration of akinesia and to some extent of analgesia, as estimated at 30 min and 60 min following the enkephalinamide injection; at the first estimation-time (10 min), taurine did not alter the duration of akinesia or that of analgesia. The median effective dose (ED50) for akinesia determined at 60 min after D-Ala2-Met-enkephalinamide was 5 times greater and that for analgesia assessed at the same time was 1.7 times greater in taurine-treated rats than the respective doses in control animals. Administration of GABA under similar experimental conditions produced a dose-dependent reduction in the duration of analgesia from the initial estimation time (10 min) following the injection of D-Ala2-Met-enkephalinamide. The ED50 for analgesia determined at 30 min after D-Ala2-Met-enkephalinamide was 3 times greater in GABA-treated rats than in control animals. Unlike the effects of taurine, GABA did not alter the duration of akinesia. Neither the duration of akinesia nor that of analgesia was modified by taurine or GABA alone in rats tested 9 min after the injection of each amino acid. These findings suggest that taurine may promote a recovery from both akinesia and analgesia, while GABA decreases only the analgesia induced by D-Ala2-Met-enkephalinamide.
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PMID:Effects of taurine and gamma-aminobutyric acid on akinesia and analgesia induced by D-Ala2-Met-enkephalinamide in rats. 724 12

Hemoglobin-(= Met-Hb)formation by local anaesthesia and local anaesthetics is still a point for discussion. Until now met-hb-aemia only was proven to develop under local anaesthetics with relationship to aniline (Benzocaine, Citanest). Since aniline does not possess any oxidative properties, met-hb-formation only can occur after metabolism (phenylhydroxylamine or para-aminophenol), first of all amino- and nitro-groups [6, 14] will be made responsible for oxidation. Because of the fact that neither the relationship to aniline nor the benzol-structure is the pre-supposition for met-hb-formation, possibly other substances with amino- or nitro-groups may induce it. In consequence of incidental cyanosis under intra and extradural analgesia we studied the met-hb-behaviour after the use of different local anaesthetics. The aniline-related bupivacaine and etidocaine were opposed to the thiophene-related carticaine. In this examination we found neither an elevation of hemoglobin by the aniline-related nor by the thiophene-related substances.
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PMID:[Met-Hb formation and local anesthesia using bupivacaine, carticaine and etidocaine (author's transl)]. 724 10

[D-Ala2]-Met-Enkephalin and [D-Ala2]-Met-Enkephalinamide were microinjected (10-30 microgram) into the midbrain ventrolateral central gray of rats. The opiate analogs produced profound analgesia in left and right facial areas, and on the hot plate test. The tail-flick test showed significant analgesia, but in a significantly smaller amount than that obtained with noxious face heating. All effects were blocked by naloxone pre-treatment. The drugs had no effect on thresholds for defense responses to high (200 Hz) and low (20 Hz) frequency aversive stimulation in midbrain areas associated with pain perception.
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PMID:Differential effects of intracerebrally microinjected enkephalin analogs on centrally versus peripherally induced pain, and evidence for a facial versus lower body analgesic effect. 745 83

5 beta-Methyl-14 beta-(p-nitrocinnamoylamino)-7,8-dihydromorphinone (MET-CAMO) and its corresponding N-cyclopropylmethyl analog, N-cyclopropylmethylnor-5 beta-methyl-14 beta-(p-nitrocinnamoylamino)- 7,8-dihydromorphinone (N-CPM-MET-CAMO) were tested in opioid receptor binding assays and in the mouse tail-flick test in order to characterize the affinity, selectivity and antinociceptive properties of these two compounds. Incubating bovine striatal membranes with either MET-CAMO or N-CPM-MET-CAMO produced a wash-resistant, concentration- and time-dependent inhibition of the binding of the mu-selective ligand, [3H]-[D-Ala2,MePhe4,Gly(ol)5]enkephalin, but with no change in delta or kappa binding. Preincubating membranes with N-CPM-MET-CAMO decreased the maximum binding value for [3H]-[D-Ala2,MePhe4,Gly(ol)5]enkephalin binding without changing the Kd value. In the mouse tail-flick assay, MET-CAMO and N-CPM-MET-CAMO did not produce any antinociception up to a dose of 100 nmol after i.c.v. administration. However, pretreatment of mice with either compound produced a time- and dose-dependent antagonism of morphine-induced antinociception. Analgesia mediated by delta or kappa opioids was not altered by either MET-CAMO or N-CPM-MET-CAMO at a dose of up to 100 nmol. The mu antagonistic effect of 1 nmol of MET-CAMO and N-CPM-MET-CAMO appeared at 8 hr and lasted up to 72 hr, with a maximal effect at 16 to 24 hr after i.c.v. administration. Pretreatment of mice with 1 nmol of MET-CAMO or N-CPM-MET-CAMO, given by i.c.v. administration at -24 hr, produced a rightward and downward shift of dose-response line of i.c.v. morphine.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:5 beta-Methyl-14 beta-(p-nitrocinnamoylamino)-7,8-dihydromorphinone and its corresponding N-cyclopropylmethyl analog, N-cyclopropylmethylnor-5 beta-methyl-14 beta-(p-nitrocinnamoylamino)- 7,8-dihydromorphinone: mu-selective irreversible opioid antagonists. 751 Nov 63

Male Wistar rats were treated with pethidine (PT) or fentanyl (FN) subcutaneously (sc) followed by intrathecal (ith) non analgesic doses of methionine- (MENK) or leucine-enkephalin (LENK), neurotensin, (NT), substance P (SP) or cholecystokinin octapeptide 26-33 (CCK-8). Then the antinociceptive effect was measured during 1 h using tail-immersion test. LENK potentiated strongly PT and FN analgesia. MENK antagonized PT analgesia only transiently 30 min after administration and transiently potentiated FN analgesia. SP and CCK-8 potentiated significantly PT analgesia, whereas NT acted biphasically: increasing and then decreasing PT analgesia. SP, CCK-8 and NT augmented FN analgesia. Naloxone inhibited analgesia elicited by the studied opioids and neuropeptides. These data show that LENK affects similarly the analgesic effects of both studied opioids, whereas MENK acted differently on PT and FN analgesia. This may suggest that individual enkephalins have different pharmacological features when interacting with different analgesics. Also NT interacted differently with pethidine and fentanyl.
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PMID:Pharmacological interaction between neuropeptides and pethidine or fentanyl in rat spinal cord. 751 84

beta-Endorphin (beta-EP) and methionine-enkephalin (M-EK) are endogenous peptides that play a role in the modification of pain perception and analgesia threshold. In order to understand more about pathophysiology of pain in association with neuroaxial blocks, we evaluated cerebrospinal fluid (CSF) concentrations of beta-EP and M-EK prior to spinal anesthesia (SA) in patients undergoing transurethral resection of prostate (TURP) to determine the correlation between preanesthesia concentrations and the duration of postoperative analgesia and opioid requirements. Twenty-five healthy patients undergoing TURP under SA were enrolled. beta-EP and M-EK were measured with a competitive radioimmunoassay. Mean preoperative beta-EP and M-EK concentrations were 153 +/- 44 and 38 +/- 5 pg/mL, respectively. Those with beta-EP concentrations > 153 pg/mL had significantly longer analgesia (P < 0.01), and lower utilization of morphine in the first postoperative day (P < 0.01). Moreover, patients with milder postoperative pain (visual analog scale score < 4/10) had significantly higher beta-EP concentrations (P < 0.01). A similar correlation was not found with M-EK values. These data suggest that preoperative CSF beta-EP, but not M-EK, concentrations correlate with the duration and quality of postoperative analgesia, as well as opioid requirements after spinal anesthesia.
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PMID:The influence of preoperative concentrations of beta-endorphin and met-enkephalin on the duration of analgesia after transurethral resection of prostate. 754 52

Irreversible opioid antagonists, when administered at small doses, require several hours to display their antagonism of antinociception mediated by opioid receptors. However, most opioid affinity ligands only need a few minutes to produce wash-resistant inhibition of opioid binding to brain membranes. Our study investigated whether the irreversible antagonists, beta-funaltrexamine (beta-FNA), 14 alpha, 14'beta-[dithiobis[(2-oxo-2,1-ethanediyl)imino]]-7,8-dihydro-N- (cyclopropylmethyl)normorphine (N-CPM-TAMO), and N-cyclopropylmethyl-5 beta-methyl- beta-(p-nitrocinnamoylamino)-7,8-dihydromorphinone (N-CPM-MET-CAMO) had any effect on morphine-induced antinociceptive tolerance before the appearance of their antagonism in the mouse tail-flick assay. All opioids were given by i.c.v. administration. The irreversible antagonists, beta-FNA (20 nmol), N-CPM-TAMO (0.5 nmol) and N-CPM-MET-CAMO (1 nmol) did not produce any antagonism of morphine-induced analgesia until at least 8 hr after administration. Pretreatment with morphine (3 nmol, -140 min) produced acute antinociceptive tolerance as demonstrated by a 45-fold rightward shift of the morphine dose-response curve. When coadministered with morphine, beta-FNA, N-CPM-TAMO and N-CPM-MET-CAMO completely prevented the development of morphine tolerance 140 min after administration in a dose-dependent manner. This preventive effect lasted for up to 420 min, during which time, morphine was given repeatedly up to four times. This antinociception produced by morphine after coadministration with irreversible antagonists was antagonized by naloxone, demonstrating that morphine-induced analgesia was still mediated by opioid receptors. The kappa- and delta-selective opioid antagonists, nor-binaltorphimine and ICI 174,864, respectively, did not block the preventive effect produced by the irreversible antagonists.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Preventing morphine antinociceptive tolerance by irreversible mu opioid antagonists before the onset of their antagonism. 775 70

The effects of intracerebroventricular injection of Anti-opioid peptide sera on oxytocin-induced enhancement of electroacupuncture (EA) analgesia were observed in this study. It was found that injection of anti-beta-endorphin serum (AEPS) alone could attenuate EA analgesia in rats. Injection of AEPS prior to intraventricular injection of oxytocin could not block the enhancement of EA analgesia by oxytocin. The antidynorphin A1-13 serum (ADYNS) alone could also reduce the EA analgesia, whereas injection of ADYNS prior to injection of oxytocin could potentiate the enhancement of EA analgesia by oxytocin. However, neither the anti-methionine enkephalin serum nor the anti-leucine enkephalin exerted any effect on the enhancement of EA analgesia by oxytocin. The above results showed that the dynorphin attenuate oxytocin-induced enhancement of EA analgesia, but Beta-endorphin and enkephalin do not affect this role of oxytocin. These data suggest the enhancement of EA analgesia by oxytocin is not dependent upon the endogenous pioid peptides in brain.
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PMID:[Effect of anti-opioid peptide sera on oxytocin-induced enhancement of electroacupuncture analgesia]. 790 15


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