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Query: UMLS:C0344307 (analgesia)
 28,200 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Intraventricular administration of the enkephalin analog, [D-Ala2]-metenkephalin, induces profound and long-lasting analgesia, as well as other opiate-like behavioral effects in the rat. This analgesia was highly dose dependent, of much greater magnitude, and about 30 times longer lasting than that produced by the naturally occurring peptide, methionine-enkephalin. The behavioral effects of the [D-Ala2] analog could be completely reversed by the opiate antagonist, naloxone, suggesting that these effects were mediated by opiate receptors. Systemic administration of naloxone alone resulted in a significant increase in pain sensitivity. These findings support the view that endogenous opiate systems may play an important role in modulating pain sensitivity.
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PMID:An analog of enkephalin having prolonged opiate-like effects in vivo. 19 Jun 83

A partially purified morphine-like peptide 'enkephalin' (PPE) extract from bovine brain elicited pronounced apparent analgesia after injection into the periaqueductal gray matter of rat brain. This analgesia was reversed by the opiate antagonist naloxone in a dose-dependent fashion. Analgesia was more rapid in onset and much shorter in duration after PPE than after morphine administration. Analgesia was elicited only by those ion exchange column fractions of PPE that competed potently for opiate receptor binding. No analgesia could be detected when PPE or morphine injections were administered at a site 2 mm lateral to the periaqueductal gray matter. The potencies of synthetic methionine- and leucine-enkephalin in eliciting analgesia were less than 1% of those of partially purified enkephalin extracts when doses of equivalent ability to compete for opiate receptor binding were compared.
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PMID:A morphine-like factor in mammalian brain: analgesic activity in rats. 20 Mar 9

Single injections of 120 micrograms of methionine-enkephalin were made into various midbrain and forebrain structures in the rat. Analgesia was observed after injections into or near the ventral, caudal midbrain periaqueductal gray matter. Seizures and other pathological electroencephalogram (EEG) changes were seen with injections into or near the forebrain dorsomedial nucleus of the thalamus. No animals with midbrain injection sites showed EEG changes, and none with forebrain injection sites were analgesic. These data, taken together with other lines of evidence, suggest that enkephalin-induced analgesia and enkephalin-induced seizures are mediated by opiate receptors that are located in different brain areas and that are pharmacologically different.
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PMID:Different brain areas mediate the analgesic and epileptic properties of enkephalin. 20 98

Morphologically similar epileptic seizures were recorded from the cortex of rats after injections into the lateral ventricle of 100 microgram of leucine-enkephalin, methionine-enkephalin, and morphine. Seizures were either greatly attenuated or blocked completely by prior systemic administration of naloxone (10 mg/kg). These findings suggest that such seizures result from an interaction of these compounds with opiate receptors in the brain. The epileptogenic potency of the enkephalins was illustrated by the observation that seizures and other pathological manifestations could still be elicited by doses as low as 10 microgram. Leucine-enkephalin was seen to have greater epiliptic potency than methionine-enkephalin. At doses of 1 microgram both enkephalins typically evoked cortical spindles resembling those seen in drowsy animals. Enkephalin-induced analgesia was seen in only one animal at the 100 microgram dose. Results obtained with repeated injections of morphine suggest that the epileptogenic effect of opiates may be subject to either tolerance or potentiation, depending on the prior occurrence of seizures. A synthesis of the present findings with several other lines of evidence suggests both that endogenous enkephalins play some role in normal mechanisms of reward, and that, when regulatory processes are disturbed, they may contribute as well to the elaboration of certain epileptic phenomena.
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PMID:Epileptic properties of leucine- and methionine-enkephalin: comparison with morphine and reversibility by naloxone. 20 15

The antinociceptive and hypothermic effects of intracisternal administration of 11 endogenous neuropeptides and morphine were evaluated in mice. Of the substances tested, only neurotensin (NT) and beta-endorphin exerted significant antinociceptive and hypothermic effects; NT was the most potent in inducing hypothermia whereas beta-endorphin was the most potent antinociceptive agent via this route of administration. Both NT, and beta-endorphin were, on a molar basis, considerably more potent antinociceptive agents than morphine, [Met]enkephalin, or [Leu]enkephalin. NT-induced analgesia and hypothermia both were significantly dose-dependent. Substance P was found to produce significant hyperalgesia and hyperthermia. Bombesin produced a significant hypothermic effect, whereas somatostatin and luteinizing hormone-releasing hormone (luliberin) produced hyperthermia. None of the other peptides studies [bradykinin, thyrotropin-releasing factor (thyroliberin), melanocyte-stimulating hormone release-inhibiting factor (melanostatin), somatostatin, [Met]enkephalin, and [Leu]enkephalin] produced any significant alterations in colonic temperature or response to a noxious stimulus with the doses tested. These data demonstrate that NT and beta-endorphin, two endogenous brain peptides, are potent in inducing hypothermia and in producing an antinociceptive state.
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PMID:Alterations in nociception and body temperature after intracisternal administration of neurotensin, beta-endorphin, other endogenous peptides, and morphine. 29 52

Acetaminophen is an effective mild analgesic and antipyretic agent. In double-blind, controlled experimental pain studies of short duration, acetaminophen is superior to placebo and produces analgesia comparable to that produced by aspirin. The frequency of adverse reactions to therapeutic doses of acetaminophen is low, as is that of aspirin. Overdosage with acetaminophen, however, may result in irreversible hepatotoxicity. Since clinical manifestations of intoxication can be of slow onset, physicians may tend to delay initiation of definitive therapy. Intravenous cysteamine, and possibly oral methionine, appear to be effective in preventing hepatotoxicity if they are administered with 10 h of drug ingestion. Physicians should be aware of the potential danger of acetaminophen overdosage and alerted to its clinical manifestations.
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PMID:Acetaminophen. 32 28

The distribution of immunoreactive enkephalin in rat brain and spinal cord was studied by immunoperoxidase staining using antiserum to leucine-enkephalin ([Leu5]-enkephalin) or methionine-enkephalin ([Met5]-enkephalin). Immunoreactive staining for both enkephalins was similarly observed in nerve fibers, terminals and cell bodies in many regions of the central nervous system. Staining of perikarya was detected in hypophysectomized rats or colchicine pretreated rats. The regions of localization for enkephalin fibers and terminals include in the forebrain: lateral septum, central nucleus of the amygdala, area CA2 of the hippocampus, certain regions of the cortex, corpus striatum, bed nucleus of the stria terminalis, hypothalamus including median eminence, thalamus and subthalamus; in the midbrain: nucleus interpeduncularis, periaqueductal gray and reticular formation; in the hind brain: nucleus parabrachialis, locus ceruleus, nuclei raphes, nucleus cochlearis, nucleus tractus solitarii, nucleus spinalis nervi trigemini, motor nuclei of certain cranial nerves, nucleus commissuralis and formatio reticularis; and in the spinal cord the substantia gelatinosa. In contrast enkephalin cell bodies appear sparsely distributed in the telencephalon, diencephalon, mesencephalon and rhombencephalon. The results of the histochemical staining show that certain structures which positively stain for enkephalin closely correspond to the distribution of opiate receptors in the brain and thus support the concept that the endogenous opiate peptides are involved in the perception of pain and analgesia. The localization of enkephalin in the preoptic-hypothalamic region together with the presence of enkephalin perikarya in the paraventricular and supraoptic nuclei suggest a role of enkephalin in the regulation of neuroendocrine functions.
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PMID:Immunohistochemical localization of enkephalin in rat brain and spinal cord. 35 1

1 A series of peptides derived from porcine lipotropin was examined for analgesic and other morphine-like properties on infusion into the cannulated third ventricle of cats.2 Lipotropin (LPH 1-91) itself produced no analgesia or other morphine-like effects when infused in a dose of 150 mug.3 C-fragment (LPH 61-91) produced strong long-lasting analgesia when infused in a dose of 10 or 20 mug; on a molar basis the potency was between 90 and 180 times that of morphine. The following morphine-like effects were also produced: shivering leading to fever, vasodilatation of the pinnae, mydriasis, opening of the palpebral fissures, tachypnoea with bouts of panting, vocalization, hyperexcitability, restlessness and catalepsy. All the effects, including analgesia, were abolished by an intraperitoneal injection of naloxone (1 mg/kg).4 Hyperglycaemia, another central effect produced by morphine, was obtained with C-fragment infused in a dose of 60 mug.5 On intravenous injection, C-fragment produced analgesia with a dose of about 200 mug/kg. Administered by this route, C-fragment was again more potent than morphine.6 C'-fragment (LPH 61-87), LPH 61-78 and LPH 61-69, either had no analgesic effect or produced weak short-lasting analgesia when infused in doses up to 100 mug.7 Methionine enkephalin (LPH 61-65) either produced very weak short-lasting analgesia or had no analgesic effect when infused in doses of between 30 and 400 mug.8N-methyl methionine enkephalin amide in which both termini of methionine enkephalin were protected against degradation by exopeptidases produced long-lasting analgesia when infused in doses of 150 to 180 mug; its analgesic potency was approximately 100 times less than that of C-fragment. Blocking only one terminus of methionine enkephalin did not appear to endow the peptide with analgesic properties. The N-methyl pentapeptide amide produced other morphine-like effects of which the most striking was catalepsy. All the effects were abolished by intraperitoneal naloxone (1 mg/kg).
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PMID:C-fragment of lipotropin--an endogenous potent analgesic peptide. 56 Aug 94

Intracerebroventricular (40-80 microgram) or i.p. (5-20 mg/kg) injection of leucine enkephalin 15 min before or after s.c. morphine administration resulted in a marked, dose-dependent enhancement of morphine analgesia as measured by the mouse tail-flick assay. Further, i.p. injection of leucine enkephalin (5 mg/kg) enhanced the analgesia produced by methadone and levorphanol in the tail-flick assay but not that by nalorphine in the abdominal constriction assay. Met- but not leu-enkephalin was an active analgesic in the abdominal constriction assay with the doses used. (D-Ala2, D-leu5)-enkephalin (1 mg/kg) treatment also markedly enhanced morphine analgesia. Similarly, administration of leucine enkephalin enhanced the development of acute tolerance and dependence produced by a single dose of morphine. Methionine enkephalin had no effect on any of the pharmacological responses produced by morphine, methadone or levorphanol. Morphine brain levels of mice after treatment with leucine or methionine enkephalin were found to be no different than those of saline-treated control animals. These results suggest that leucine enkephalin may be an important and potent physiological modulator of narcotic efficacy.
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PMID:Differential effects of leucine and methionine enkephalin on morphine-induced analgesia, acute tolerance and dependence. 56 99

Methionine-enkephalin (0.2--20 microgram/rat) and leucine-enkephalin (1--20 microgram/rat) produced a dose-related and naloxone-antagonizable analgesia in the tail-pinch test, when microinjected into the nucleus reticularis gigantocellularis (NRGC) and nucleus reticularis paragigantocellularis (NRPG) of the medulla oblongata of the rat. The median analgesic doses were 1.4 and 4.8 microgram/rat for methionine- leucine-enkephalin, respectively. The possibility that the endogenous enkephalins play a part as pain control substances or modulators in the NRGC and NRPG was discussed.
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PMID:Analgesia by enkephalins injected into the nucleus reticularis gigantocellularis of rat medulla oblongata. 65 22


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