Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0030193 (pain)
 261,466 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Selective agonists for mu- and kappa-opioid receptor types were infused, bilaterally, into the intralaminar central lateral nucleus of the rat. Subcataleptic doses of the mu-agonist, DAGO (0.25 and 1.0 microgram), elevated tailshock threshold for eliciting pain vocalization and motor responses. The hyperalgesic effect of U50,488 is not likely to be the result of antagonist action at a mu 2-isoreceptor; the general mu-antagonist, naloxone, and its less lipophilic quaternary analogue, both failed to produce a significant reduction in pain thresholds. Paralleling their effects on pain, DAGO and U50,488 elevated and reduced, respectively, lateral hypothalamic electrical stimulation threshold for positive reinforcement. These results suggest that medial thalamic opioid mechanisms are not exclusively involved in pain modulation but may generally regulate the responsiveness of the organism to motivating stimuli. Moreover, mu- and kappa-receptors may mediate opposite behavioral effects of opioid peptides.
 ...
PMID:Medial thalamic injection of opioid agonists: mu-agonist increases while kappa-agonist decreases stimulus thresholds for pain and reward. 283 99

Clinically, patients often demonstrate incomplete cross-tolerance between opiate analgesics. Although dispositional and pharmacokinetic factors may be a factor, our results suggest that differences in selectivity of various opioids for those opioid receptor subtypes involved in analgesia, mu 1, kappa and delta, also play an important role. In binding studies, levorphanol potently labelled all 3 classes whereas morphine was relatively selective for mu sites. Levorphanol infusions yielded tolerance to both morphine and levorphanol while morphine infusions selectively produced tolerance to morphine. This unidirectional tolerance might be due to the selectivity of morphine for mu receptors compared to levorphanol's ability to interact more potently with other relevant receptor subtypes. These observations raise the possibility that the order in which different opioid analgesics are administered may be of clinical significance.
Pain 1988 May
PMID:Unidirectional analgesic cross-tolerance between morphine and levorphanol in the rat. 283 16

The effect of central administration of delta-sleep-inducing peptide (DSIP) on nociceptive responses was evaluated in mice and rats. DSIP, administered intracerebroventricularly or intracisternally to mice, produced a significant dose-dependent antinociceptive effect in the tail-pinch and hot-plate tests. Intrathecal administration of DSIP did not produce such an effect. The antinociceptive effect of DSIP was blocked by pretreatment with the opioid antagonist, naloxone. Moreover, DSIP did not produce an antinociceptive effect in morphine-tolerant mice. Similar antinociceptive effects of DSIP were observed in rats. These results suggest that DSIP produces an antinociceptive effect by acting at the supraspinal level and that this effect is mediated via the opioid receptor, either directly or indirectly. DSIP may play an important role in pain regulation in the central nervous system.
 ...
PMID:Potent antinociceptive effect of centrally administered delta-sleep-inducing peptide (DSIP). 285 64

An unbiased preference conditioning procedure was used to characterize and compare the motivational effects of opioids in naive rats and those suffering from the prolonged pain associated with Freund's adjuvant (FA)-induced inflammation of one hind limb. The mu-opioid agonist morphine functioned as a reinforcer in naive animals, producing marked preferences for the drug-paired place. Similarly, rats injected with FA 7 days prior to conditioning exhibited a preference for the morphine place, and the magnitude of this effect did not differ between groups. Administration of the kappa-opioid receptor agonist U-69593 to naive rats produced dose-related place aversions. The aversive effect of this kappa-agonist was, however, abolished in FA-treated rats. Thus, regardless of the dose administered, U-69593 produced conditioning similar to that observed in response to saline. These data suggest that kappa-agonists may lack aversive effects in subjects experiencing prolonged noxious stimulation, and as such may be effective therapeutic agents in the management of chronic pain states.
Pain 1988 Nov
PMID:Motivational effects of opioids in an animal model of prolonged inflammatory pain: alteration in the effects of kappa- but not of mu-receptor agonists. 285 21

Inoculation of rats with Mycobacterium butyricum produced an arthritis of the limbs which revealed an enhanced sensitivity to noxious mechanical pressure (hyperalgesia). Arthritic rats displayed a pronounced rise in immunoreactive dynorphin in lumbo-sacral spinal cord which correlated both with the intensity and time-course of this hyperalgesia. MR-2266, a relatively preferential antagonist at the chi-opioid receptor (at which dynorphin is considered to act) potentiated this hyperalgesia. In contrast, MR 2267 (its inactive stereo-isomer) was ineffective. Further, naloxone (a weak chi-antagonist), and ICI 154,129 (a preferential delta-antagonist) were, in each case, inactive. The data demonstrate a pronounced response of spinal dynorphin to chronic arthritic pain in the rat. In addition, they raise the possibility of a function of spinal DYN, via a chi-receptor, in the modulation of chronic arthritic pain.
 ...
PMID:Spinal cord dynorphin may modulate nociception via a kappa-opioid receptor in chronic arthritic rats. 286 57

Like other opioids, the dynorphins play a role in wide variety of physiological parameters, including pain regulation, motor activity, cardiovascular regulation, respiration, temperature regulation, feeding behavior, hormone balance, and the response to shock or stress. The dynorphins are unusual if not unique, however, in that they frequently modulate the activity of other opioids, rather than having direct effects themselves. Thus, they are not analgesic in brain, yet they antagonize opioid analgesia in naive animals and potentiate it in tolerant animals. They have little or no effect by themselves on temperature regulation or respiration, but they enhance the acute effects of morphine on these parameters. Their beneficial effects on stroke are like those of opioid antagonists rather than like agonists. Consistent with such a wide variety of physiological effects, the dynorphins bind to all three of the major opioid receptor types in brain, mu, delta, and kappa, though they exhibit some preference toward kappa sites. They also seem to interact with other physiologically relevant sites; though on the basis of their sensitivity to des-Tyr fragments of dynorphine and/or their insensitivity to naloxone, these sites have been termed "non-opioid". No second messenger systems have been directly associated with dynorphine binding, but several likely candidates exist.
 ...
PMID:Pharmacology of dynorphin. 289 33

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.
 ...
PMID:[D-Pro10]-dynorphin(1-11) is a kappa-selective opioid analgesic in mice. 289 27

1. The effects of an intrathecally administered benzodiazepine receptor (BZR) agonist (midazolam, up to 50 micrograms), antagonist (flumazenil, Ro 15-1788, 5 micrograms) and inverse agonist (Ro 19-4603, 15 micrograms) on nociception and on morphine-induced antinociception were studied in rats. 2. By themselves, none of these compounds significantly altered pain threshold. 3. The BZR agonist midazolam enhanced the morphine-induced antinociceptive effect whereas the antagonist flumazenil did not alter it. In contrast, the BZR inverse agonist Ro 19-4603 decreased the morphine-induced antinociceptive effect. 4. Naloxone (1 mg kg-1 i.p.) completely reversed all these effects. 5. These results demonstrate that BZR agonists and inverse agonists are able to affect, by allosteric up- or down-modulation of gamma-aminobutyric acidA (GABAA)-receptors, the transmission of nociceptive information at the spinal cord level, when this transmission is depressed by mu-opioid receptor activation.
 ...
PMID:Effects of an intrathecally administered benzodiazepine receptor agonist, antagonist and inverse agonist on morphine-induced inhibition of a spinal nociceptive reflex. 289 60

The sensitivity to painful and sexual stimuli in male rats was markedly suppressed immediately after ejaculation and enhanced after the postejaculatory refractory period. The suppression of pain sensitivity induced by sexual activity was reversed, but sexual behavior was only slightly affected by intraperitoneal (i.p.) injection of the opioid antagonist naloxone (5 mg). Plasma concentrations of beta-endorphin-like immunoreactivity were unaffected by sexual activity. Injection of beta-endorphin (10 micrograms s.c.) markedly raised plasma concentrations of beta-endorphin-like immunoreactivity within 1 min of injection but did not affect the sensitivity to painful stimulation or the display of sexual behavior. It is suggested that while ejaculation may activate opioid receptor mechanisms, which affect the sensitivity to painful, but not sexual, stimuli, elevation of beta-endorphin in the blood does not affect the sensitivity to either sexual or painful stimuli in male rats.
 ...
PMID:Sexual behavior induces naloxone-reversible hypoalgesia in male rats. 296 14

The motility, pain-threshold and opioid receptor activities of the synaptic membrane in mice showing conditioned suppression of motility were compared with those in mice given only electric footshock. Electric footshock caused analgesia and a decrease in motility, both of which were partially reversed by administration of high doses of naloxone. In contrast, mice exhibited a marked suppression of motility (conditioned suppression) but not analgesia when placed in the same environment 24 hr after the electric footshock in which the animals received the electric footshock. In the electric footshock group, the [3H]-naloxone binding capacity at low affinity site was increased. These results suggest that the increase in [3H]-naloxone binding capacity may play an important role in the behavioral changes of electric footshock group, but not conditioned suppression group.
 ...
PMID:Differences of alteration in opioid systems induced by conditioned suppression and electric footshock in mice. 298 3


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>