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)

Male rats were injected s.c. once daily during the first week of life with beta-endorphin (BE), morphiceptin, the antiopiate Tyr-MIF-1 (Tyr-Pro-Leu-Gly-NH2), or one of the two opiate peptides in combination Tyr-MIF-1. Pups treated with neonatal BE removed their tails from a series of increasingly hot water baths significantly faster than controls on day 9, confirming our earlier studies. In addition, we found that Tyr-MIF-1 blocked this effect of BE. At 4.5 months, latency to lick a hindpaw in the hot-plate test was significantly faster in groups given BE alone, morphiceptin alone, or the control vehicle than in any of the 3 groups given Tyr-MIF-1. At 6 months the two groups given opiate peptides alone showed faster tail-flick latencies than the controls and the groups given Tyr-MIF-1. These results indicated that the long-term nociceptive changes induced by the opiate peptides were opposite to those induced by Tyr-MIF-1. Mean tail-flick latencies of the groups on day 9 correlated well with hot-plate and tail-flick scores in adulthood, indicating that the effects of the peptides were persistent. The neonatal peptide treatments did not differentially affect the analgesia induced by the stress of footshock or warm-water swim. Rats given either of the opiate peptides alone tended to fall off a rotorod faster than those in the other groups. These results support the role of Tyr-MIF-1 as an antiopiate and further illustrate the long-term effects of neonatally administered peptides.
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PMID:Long-term hyperalgesia induced by neonatal beta-endorphin and morphiceptin is blocked by neonatal Tyr-MIF-1. 288 15

The blood-brain barrier is capable of transporting peptides with anti-opiate (Tyr-MIF-1) and opiate (enkephalins) activity out of the central nervous system. The relationship of this transport system to the various actions of opiates remains unexplored. This study examined the relationship between the rate of transport and opiate-induced analgesia. Both restraint, a stress that provokes an opiate-mediated analgesia, and the administration of morphine (12 mg/kg, i.p.) each induced an inhibition in the rate of transport. Such inhibition exhibited specificity, since the saturable, brain to blood transport of iodide remained unaltered. However, it was possible to dissociate analgesia and inhibition of transport. The onset and peak of analgesia, as measured by tail-flick latency induced by morphine, preceded the onset and peak of the inhibition of transport. Naltrexone, which blocks opiate-mediated analgesia, also induced inhibition of transport without any significant effect on tail-flick latency. (-) Naloxone but not (+) naloxone also weakly inhibited transport. Deprivation of food and water, associated with analgesia possibly mediated by the opiate, beta-endorphin, which is not transported out of the brain by this system, did not alter transport. These results suggest that while inhibition of transport and analgesia may occur together, these events probably represent two separate aspects of the action of opiates, that may even be mediated by separate receptor sites or peptides in the opiate family.
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PMID:Analgesia and the blood-brain barrier transport system for Tyr-MIF-1/enkephalins: evidence for a dissociation. 289 31

Three forms of stress-induced analgesia (electric shock, forced water-swim and novelty) were used to examine the nature of the endogenous antiopiate system. It was hypothesized that a role of the antiopiate system may be to regulate the extent of antinociception within varying environments. The antiopiate properties of Tyr-MIF-1 (Tyr-Pro-Leu-Gly-NH2), which were manifest by reduction of opiate analgesia in mice on a hot-plate, were best expressed within a defined range of intensities. In each of the 3 analgesic situations, pre-administration of Tyr-MIF-1 (0.1 mg/kg) resulted in an antinociceptive effect after low to moderate stress but not after more intense stress. These observations indicate that the antiopiate system can function differentially under various environmental conditions, thus ensuring that the organism's responses to its perception of the immediate environment are appropriate and specific.
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PMID:Differential activity of the endogenous antiopiate Tyr-MIF-1 after various intensities of stress. 289 40

The effects of intracerebroventricular (i.c.v.) administrations of the putative follicle stimulating hormone (FSH) suppressing gonadal steroid, 3 alpha-hydroxy-4-pregnen-20-one (3A4P) on the nociceptive responses of male mice were examined. This allylic steroid elicited significant, dose-dependent (0.001-1.0 micrograms) analgesic responses for 90-150 min after injection. These analgesic effects of 3A4P were stereospecific, the stereoisomer, 3 beta-hydroxy-4-pregnen-20-one (3B4P) failing to affect the nociceptive responses. The analgesic effects of 3A4P were blocked by peripheral administrations of the GABA antagonists, bicuculline and picrotoxin, and reduced by the benzodiazepine antagonist, Ro 15-1788. The exogenous opiate antagonist, naloxone, and the putative endogenous opioid antagonist, Tyr-MIF-1 (Pro-Leu-Gly-amide), also reduced 3A4P-induced analgesia, while i.c.v. administration of 3A4P (0.001 and 0.01 micrograms) itself attenuated the analgesic effects arising from peripheral administrations of opiate receptor agonist, morphine. In addition, the calcium channel antagonists, nifedipine and verapamil, enhanced 3A4P-induced analgesia but had no evident effects on the actions of 3B4P. These results suggest that the central analgesic effects of the FSH-suppressing steroid, 3A4P, arise via benzodiazepine--GABA--opiate mechanisms and calcium channels. These findings also suggest possible central modes of action whereby 3A4P may elicit selective suppression of FSH.
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PMID:Analgesic effects of the putative FSH-suppressing gonadal steroid, 3 alpha-hydroxy-4-pregnen-20-one: possible modes of action. 314 22

A tabular synopsis is presented for articles concerned with the effects of peptides on the central nervous system that appeared in the journal Peptides from 1980-1985. A table arranged alphabetically by peptide and one arranged by effects, both listing routes of injection, species, direction of change, and qualifying notes, provides easy cross-referencing of peptides and their effects. Over 80 peptides and over 135 effects are listed. The list of peptides includes, but is not limited to: ACTH, angiotensin, bombesin, bradykinin, calcitonin, casomorphin, CCK, ceruletide, CGRP, CRF, dermorphin, DSIP, dynorphin, endorphins, enkephalins, GRF, gastrin, LHRH, litorin, metkephamid, MIF-l, motilin, MSH, NPY, NT, oxytocin, ranatensin, sauvagine, substances P and K, somatostatin, TRH, VIP, vasopressin, and vasotocin. The list of effects includes, but is not limited to: aggression, alcohol, analgesia, attention, avoidance, behavior, cardiovascular regulation, catalepsy, conditioned behavior, convulsions, dopamine binding and metabolism, discrimination, drinking, EEG, exploration, feeding, fever, gastric secretion, GI motility, grooming, learning, locomotor behavior, mating, memory, neuronal activity, open field, operant behavior, rearing, respiration, satiety, scratching, seizure, sleep, stereotypy, temperature, thermoregulation and tolerance.
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PMID:Central nervous system effects of peptides, 1980-1985: a cross-listing of peptides and their central actions from the first six years of the journal Peptides. 353 8

Acute intraventricular administration of human beta-endorphin (15 microgram) produced analgesia, hypothermia and catalepsy in male Sprague-Dawley rats. Injections of beta-endorphin given every 8 hr for 3 days resulted in the development of tolerance to all of the above mentioned pharmacological effects. Tolerance developed rapidly to the hypothermic effect and less rapidly to the analgesic and cataleptic effects. After the third or the fourth injection of beta-endorphin, pronounced hyperthermia, rather than hypothermia, was observed. After seven or eight injections of beta-endorphin, tolerance to the analgesic effect was complete and the cataleptic effect was reduced to 50% of the original. Daily s.c. administration of Pro-Leu-Gly-NH2 (MIF) or cyclo(Leu-Gly) (2 mg/kg each) blocked the development of tolerance to the analgesic and cataleptic effects of beta-endorphin. The hyperthermic effect of beta-endorphin in beta-endorphin-tolerant rats was partially blocked by both MIF and cyclo(Leu-Gly). Multiple injections of MIF or cyclo(Leu-Gly) did not alter beta-endorphin-induced analgesia, catalepsy and hypothermia in rats which were given repeated intraventricular injections of saline. Since MIF is a naturally occurring peptide of hypothalamic origin, these studies suggest that the hypothalamus may be an important site in regulating the pharmacological effects of chronically administered endogenous opiates.
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PMID:Inhibition of tolerance to the pharmacological effects of human beta-endorphin by prolyl-leucyl-glycinamide and cyclo(leucylglycine) in the rat. 611 70

The effects of prolyl-leucyl-glycinamide (melanotropin release inhibiting factor, MIF) and cyclo(Leu-Gly) on development of tolerance to the analgesic, locomotor stimulant and depressant effects of morphine were investigated in the mouse. Mice were made tolerant to morphine by subcutaneous implantation of pellet (each pellet contained 75 mg of morphine free base) for three days. Both MIF and cyclo(Leu-Gly) inhibited the development of tolerance to the analgesic response to a challenge dose of morphine in peptide-treated as compared to vehicle-treated morphine-tolerant mice. Morphine in a small dose (10 mg/kg) depressed spontaneous motor activity, while, in a larger dose (80 mg/kg), increased the motor activity. Implantation of a morphine pellet resulted in the development of tolerance to both the locomotor depressant and stimulant effects of morphine. Administration of MIF or cyclo(Leu-Gly) during induction of tolerance in doses (2 mg/kg/day for 3 days) that inhibited the development of tolerance to morphine-induced analgesia and locomotor depressant activity, did not alter the development of tolerance to the locomotor stimulant effect. These studies indicate that the development of tolerance to the analgesic and locomotor depressant effect of morphine may involve similar mechanisms, whereas, tolerance to the locomotor stimulant effect of morphine may be mediated via a different mechanism.
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PMID:Hypothalamic peptide hormone, prolyl-leucyl-glycinamide and analog, inhibit tolerance to the analgesic and locomotor depressant but not to the locomotor stimulant effects of morphine in the mouse. 612 86

Prolyl-leucyl-glycinamide (MIF-1), the C-terminal tripeptide of oxytocin, and naloxone were administered intracranially (IC) to goldfish (Carassius auratus) in doses of 0.001, 0.01, 0.1, 1.0 and 10.0 mg/kg and compared to a diluent control group for their ability to reduce the effects of morphine (30 mg/kg IC) in an assay measuring analgesia to electric shock. Threshold levels of pain were determined by the voltage necessary to produce an agitated swimming response (ASR). Both MIF-1 and naloxone were found to significantly reduce the analgesic effects of morphine when compared to the diluent control group. Similar dose-response curves in an apparent sine-wave pattern were noted with both MIF-1 and naloxone when comparisons were made both at 20 minutes after administration of morphine and over the entire 150 minutes of the experiment. The results support the evidence that MIF-1 can act as an opiate antagonist.
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PMID:Similar antagonism of morphine analgesia by MIF-1 and naloxone in Carassius auratus. 612 44

MIF-1 (Pro-Leu-Gly-NH2), a hypothalamic tripeptide, has been demonstrated to stimulate naloxone in antagonizing the effects of opioid peptides in a number of experimental systems including enkephalin-induced analgesia in the tail-flick assay, beta-endorphin induced hypothermia and hypomotility, deprivation-induced drinking, and analgesia in goldfish. MIF-1, however, has no effect upon the activity of enkephalins in the mouse vas deferens or enkephalin binding in the rat striatum. We have studied the interactions of MIF-1 with Leu5-enkephalin (Leu5-ENK) in the conscious, chronically instrumented dog. Although naloxone inhibits both the elevations of heart rate and blood pressure produced by IV Leu5-ENK in the conscious state and the depressions in these variables produced by Leu5-ENK after pentobarbital anesthesia, MIF-1 has no effect upon the Leu5-ENK response in either state. However, both naloxone and MIF-1 seem to raise mean arterial pressure in the conscious dog. These results indicate that MIF-1 does not act like naloxone in antagonizing the peripheral effects of Leu5-ENK and lend further support to the existence of mechanistic differences among opiate-mediated behavior, analgesia, and cardiovascular activity.
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PMID:MIF-1 does not act like naloxone in antagonizing the cardiovascular activity of leucine-enkephalin in the conscious dog. 613 37

Prolyl-leucyl-glycinamide (MIF-1) has been observed to inhibit the analgesic effect of morphine in a series of animal studies. In the present study, the naloxone-like properties of MIF-1 were assessed in human subjects. Eight men received a capsule containing 60 mg of MIF-1 or placebo followed one hour later by a 10 mg intramuscular injection of morphine in a double-blind, crossover design at two visits 4 weeks apart. Experimental pain was induced by the cold pressor test administered 45, 75, 120 and 180 min after the morphine. Each subject recorded severity of pain on a 100 mm line scale every 5 sec during the 120 sec his foot was immersed in the cold water tank and during the 60 seconds immediately following its removal. On a third visit, baseline values were measured in the absence of morphine, MIF-1 or placebo. Analysis of variance revealed that MIF-1 resulted in significantly higher scores (less analgesia) compared with placebo when measured at 45 and 75 min after morphine during the immersion phase and during all four times the subjects were evaluated during the removal phase. The results indicate that MIF-1 can act in humans as an opiate antagonist.
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PMID:Antagonism of morphine analgesia by prolyl-leucyl-glycinamide (MIF-1) in humans. 615 72


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