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)

Area tempestas (AT) is a forebrain area involved in the genesis and generalization of clonic convulsions in rats. This study reports that upon AT application opiates and opioid peptides produce antinociceptive effects as measured with the hot-plate (HP) and tail-flick (TF) tests in rats. Unilateral infusion of mu and kappa agonists into AT at doses in the nanogram range delayed the latency to respond for the contralateral paws in the HP test (Emax, 67-91 degrees of analgesia), beginning 1 to 5 min after application. A smaller effect was observed after the Leu-enkephalin, [D-Ala2,D-Leu5][enkephalin and D-Pen2,D-Pen5]enkephalin. No effect was observed after Met-enkephalin. In the TF test, unilateral application of mu and kappa agonists in the nanogram range produced antinociception with Emax values of 43 to 62 degrees of analgesia, beginning 5 to 15 min after infusion. No significant effect was found after unilateral infusion of delta agonists. Infusion into AT (10 min before) of naltrexone (2-4 ng), ICI 154, 129 (1-10 ng) and WIN 44,441-3 (2-20 ng) antagonized the antinociception evoked by locally applied morphine (25 ng), [D-Pen2,D-Pen5]enkephalin (50 ng) and U 50,488 (100 ng), respectively. In addition, antinociception induced by systemic morphine (2.5 mg/kg sc) was antagonized by subsequent (23 min) unilateral application of naltrexone (15 ng). In the HP test, a reduction of the antinociceptive effect of morphine was obtained for both ipsilateral and contralateral paws after the antagonists.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Antinociceptive action of opiates and opioid peptides after unilateral microinjection into area tempestas in rats. 166 76

The contents of Met-enkephalin (MEK) and Leu-enkephalin (LEK) in striatum and MEK in hypothalamus of rat increased markedly after electroacupuncture analgesia (EAA). Intraperitoneal injection of phentolamine, a blocker of alpha receptor, potentiated the EAA and abolished the effects of EA increasing MEK and LEK contents; while injection of propranolol, a blocker of beta receptor, partially inhibited the EAA, as well as abolished the effects of EA increasing MEK and LEK concentrations in the striatum and the hypothalamus, and also elevated the MEK and LEK contents in hippocampus and MEK level in cortex. The results indicate that EA regulates metabolism of MEK and LEK, as well as EAA partially via alpha and beta receptors.
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PMID:Effects of phentolamine and propranolol on the changes of pain threshold and contents of MEK and LEK in rat brain after EA. 261 60

Electrical stimulation of the ventral midbrain periaqueductal grey (PAG) elicited an antinociception (analgesia) in freely moving rats. Stimulated animals displayed a pronounced decrease in levels of immunoreactive (ir)-beta-endorphin (beta-EP) in the midbrain PAG. This depletion was selective in that: animals placed in the chamber and not stimulated revealed neither an analgesia nor an alteration in levels of ir-beta-EP. No change in levels of ir-beta-EP was detectable in other brain regions. Both stimulated rats and rats placed in the chamber and not stimulated revealed a rise in circulating ir-beta-EP: the magnitude of this rise did not, however, differ between these groups. Levels of ir-Met-enkephalin, ir-Leu-enkephalin and ir-dynorphin A were modified neither in the PAG nor in other CNS tissues. The data demonstrate that electrical stimulation of the midbrain PAG selectively influences (presumably activates) pools of beta-EP therein. Together with our finding that destruction of PAG-localized beta-EP neurones to block stimulation-analgesia, the data suggest that an activation of intrinsic pools of beta-EP underlies stimulation-produced analgesia elicited from the PAG in the rat.
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PMID:Activation of periaqueductal grey pools of beta-endorphin by analgetic electrical stimulation in freely moving rats. 288 14

The synthetic opioid agonist [D-Pro10]-dynorphin(1-11) (DPDYN) binds kappa receptors with both high affinity and selectivity in vitro. We have examined the in vivo characteristics (i.e., analgesic properties) of the peptide in mice. The analgesic effects of i.c.v. administered DPDYN were determined in two nociceptive tests, involving thermal cutaneous (tail-flick) and chemical visceral (AcOH-induced writhing) stimuli, in which mu and kappa receptors are known to be activated differentially. The antinociceptive action of DPDYN was compared with that of 1) morphine and U-50,488H, which are, respectively, the prototypical mu and kappa agonists, 2) dynorphin A which is the endogenous parent peptide and 3) Leu-enkephalin, which represents the N-terminal sequence of DPDYN. DPDYN did not show any activity against thermal stimulus but, in contrast, produced a dose-related effect against chemical pain. In the AcOH-writhing test, there was no significant cross-tolerance between morphine and DPDYN in mice made tolerant to morphine. Pretreatment with low doses of s.c. naloxone (less than 1 mg/kg) antagonized completely the antinociceptive action of morphine but only partially reversed the analgesic action of DPDYN. In gastrointestinal studies, DPDYN as well as U-50,488H were ineffective (maximum effect lower than 25%) in inhibiting intestinal transit in mice, in contrast to morphine which produced a dose-related antitransit effect reaching 100%. These data indicate that the in vivo properties, and particularly analgesia, of i.c.v. administered DPDYN are mediated by a "non-mu" (presumably kappa) opioid receptor at the supraspinal level of the opioid system of the mouse.
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PMID:[D-Pro10]-dynorphin(1-11) is a kappa-selective opioid analgesic in mice. 289 27

Enkephalin analogues of tyrosyl group on the N-terminal and Phe-ol or phenylethylamine (PHA) group on the C-terminal which are connected with different chain length were tested for their activities in vitro and in vivo. The inhibitory effect of the synthetic peptides on the electrically evoked contractions of isolated longitudinal muscle strips of guinea pig ileum were weaker than that of morphine or Leu-enkephalin and tended to decrease by increasing the number of methylene group,-(CH2)n-, n = 1-5, between N- and C-terminal. Compounds with PHA group on the C-terminal, n = 4 and 5, showed the least activity. The effect of peptides with short chains of methylene groups, n = 1 or 2, and Phe-ol on the C-terminal were antagonized by naloxone but others were insensitive to naloxone. Differing from in vitro activity, compounds with PHA on the C-terminal with a chain of 4 methylene groups produced short lasting analgesia after i.c.v. injection as well as the compounds with Phe-ol on the C-terminal and 1 or 2 methylene groups. The analgesic effect of these compounds were completely antagonized by naloxone. At a high i.c.v. dose, all the synthetic peptides, except the one with PHA on the C-terminal with a chain of 4 methylene group, produced convulsions and/or ipsilateral rotation to the injection side. These behavioral effects were not antagonized by naloxone. Thus, minor alterations in the chemical structure of enkephalin analogues resulted in the changes of their receptor selectivity and potencies in vitro and in vivo.
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PMID:Involvement of different receptor subtypes for the production of in vitro and in vivo effects in a series of synthetic enkephalin analogues. 300 43

Recent in vivo and in vitro studies have shown the involvement of gamma-aminobutyric acid (GABA) in analgesia. We investigated if the analgesia induced by an acute valproic acid (VPA) administration might be related to the activation of the enkephalinergic system. VPA administration (i.p.) induces 30 min after treatment a significant and dose-dependent increase of Leu-enkephalin and Met-enkephalin in the striatum, hypothalamus, cortex and brainstem. In the hypophysis no modification was observed for these two neuropeptides. The Met-enkephalin-Arg-Gly-Leu levels are affected by VPA administration in a more complex pattern. Such results suggest the implication of an enkephalinergic system in GABAergic analgesia.
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PMID:Analgesic properties of valproic acid might be related to activation of pro-enkephalin system in rat brain. 310 87

The distribution of methionine-enkephalin-Arg6-Gly7-Leu8, a unique peptide derived from proenkephalin A in the rat brainstem, was studied immunocytochemically by using a highly specific antiserum to this octapeptide sequence. Immunoreactive perikarya with various shapes and sizes were detected in many regions of the rat brainstem. Dense accumulation of immunoreactive perikarya and fibers was seen in the nuclei associated with special sensory and visceral functions, such as the interpeduncular nucleus, the parabrachial nucleus, the nucleus of the solitary tract, and the nucleus of the spinal tract of the trigeminal nerve. Clusters of methionine-enkephalin-Arg6-Gly7-Leu8-like immunoreactive perikarya and fibers were observed in certain areas considered to play a role in nociception and analgesia, such as the central gray of the midbrain central gray and the raphe magnus nucleus. Some methionine-enkephalin-Arg6-Gly7-Leu8-like immunoreactive perikarya were distributed in the lateral reticular nucleus, the nucleus of the solitary tract, and the raphe magnus nucleus, where monoaminergic neurons were also detected. In addition to the previously reported enkephalinergic cells, we found many methionine-enkephalin-Arg6-Gly7-Leu8 containing neurons; the rostral and caudal linear nucleus of raphe, the median raphe nucleus, entire length of the raphe magnus nucleus, the medial longitudinal fasciculus, the cuneate nucleus, the external cuneate nucleus, the gracile nucleus, and the area postrema. The wide distribution of this octapeptide-like immunoreactivity reflected neurons expressing the preproenkephalin A gene distributed more widely than previously reported and that innervated many regions.
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PMID:Immunocytochemical distribution of met-enkephalin-Arg6-Gly7-Leu8 in the rat lower brainstem. 330 99

Endogenous opioid peptides have been implicated in stress-induced analgesia and stress-induced feeding behavior. An earlier study from our laboratory showed that rats subjected to cold swim stress consumed significantly more food compared to controls. The present study describes changes in the levels of various opioid peptides in the central nervous system and periphery due to cold swim stress. Male Sprague-Dawley rats were subjected to cold swim stress (1 degree C for 5 min), then sacrificed by decapitation; brain, pituitary, adrenals and plasma were collected. Tissue extracts were assayed for opioid peptides by RIA. Cold swim stress resulted in analgesia which could be blocked by prior administration of naloxone, as observed by a tail-flick latency test. Cold swim stress caused a 42% decrease in pituitary beta-endorphin, but increased the level of this peptide in the hypothalamus and plasma by 36% and 337%, respectively. Dynorphin level decreased by 62% in the hypothalamus, but was not affected in the pituitary. Levels of Leu-enkephalin and Met-enkephalin decreased in the adrenal gland by 37% and 18%, respectively, but were not significantly affected in the CNS. These results indicate that cold swim stress has a differential effect on the level of CNS and peripheral opioid peptides, and that both central and peripheral opioid peptides may be important in stress-induced analgesia and feeding behavior.
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PMID:Cold swim stress-induced changes in the levels of opioid peptides in the rat CNS and peripheral tissues. 335 22

D-Ala-D-Leu-enkephalin (DADL) is a pentapeptide which, compared to morphine, preferentially binds to the delta receptor. We compared the analgesic and side effects of intrathecal (i.t.) DADL and i.t. morphine sulfate (MS) in 10 tolerant cancer patients with chronic pain at or below the T12 level who were receiving inadequate relief or unacceptable side effects from systemic opiates. These patients were given i.t. DADL and i.t. MS in a randomized, double-blind, cross-over study on separate days at least 1 day apart. I.t. DADL produced analgesia in all patients tested. Total pain relief was greater with DADL than MS in 6 patients, equal in 1 patient and less with DADL in 3. Side effects, most commonly drowsiness, were similar with both MS and DADL and suggest supraspinal effects by both drugs. At the doses given i.t. DADL produced effective pain relief in patients tolerant to systemic opiates although no significant difference in analgesic efficacy between MS and DADL was observed. Studies of the relative analgesic potency of i.t. DADL in man are necessary to fully assess its value in those patients tolerant to systemic or i.t. opiates.
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PMID:The analgesic efficacy of intrathecal D-Ala2-D-Leu5-enkephalin in cancer patients with chronic pain. 390 16

A comparison was carried out of the effectiveness of intracerebroventricular or intraperitoneal administration of Leu-enkephalin to affect acquisition of a one-way active avoidance response, locomotor activity or shock sensitivity. Leu-enkephalin impaired acquisition of the avoidance response only when administered peripherally. In contrast, either central or peripheral administration of Leu-enkephalin increased locomotor activity in the open field, and Leu-enkephalin also produced analgesia when administered directly into the brain. The pattern of results suggests that Leu-enkephalin acts at a peripheral site to influence avoidance conditioning.
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PMID:Central versus peripheral actions of Leu-enkephalin on acquisition of a one-way active avoidance response in rats. 398 16


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