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)

In laboratory animals and humans, pregnancy is associated with opioid-mediated elevations in the threshold for responsiveness to aversive stimuli. Previous pharmacological analysis has demonstrated that this analgesia results, at least in part, from the activation of spinal cord kappa opioid receptors utilizing dynorphin as the major opioid substrate. The present report demonstrates that during late pregnancy, the content of spinal dynorphin A(1-17 and 1-8) is altered in a region-specific fashion. As a result, levels of dynorphin peptides are elevated, but only in the lumbar spinal region. In parturient animals, lumbar levels of dynorphin A(1-8) remained elevated but there was an additional increment in the content of dynorphin A(1-17). During late gestation, spinal content of Met-enkephalin and its precursor are also elevated, but, in contrast to dynorphin peptides, there is no interaction between condition and spinal level. Possible analgesic synergy between mu-delta and kappa opioid receptor systems is discussed. It is concluded that some parameter(s) of the pregnant condition triggers the activation of a spinal cord dynorphin system that attenuates the pain associated with late pregnancy and labor.
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PMID:Spinal cord dynorphin: positive region-specific modulation during pregnancy and parturition. 810 19

The present study examined the effects of the competitive NMDA antagonist, NPC 12626, on the analgesic effects of the specific kappa opiate receptor agonist, U69,593, in male deer mice. Intraperitoneal (i.p.) administration of NPC 12626 had no effect on the basal nociceptive sensitivity of reproductive male deer mice, as measured by latency of response to a thermal (50 degrees C) surface. NPC 12626 dose-dependently (0.05-1.0 mg/kg) reduced U69,593-induced analgesia. NPC 12626 at 1.0 mg/kg attenuated U69,593-induced analgesia in a manner comparable to that produced by the specific kappa opiate antagonist, nor-binaltorphimine. In contrast, this dose of NPC 12626 potentiated the analgesia produced by the predominantly mu agonist morphine (1.0 mg/kg). The non-competitive NMDA antagonist, MK-801, which has been previously indicated to affect kappa opiate analgesia, significantly reduced at 1.0 mg/kg, but did not block, the analgesia produced by U69,593 and in contrast to NPC 12626, slightly reduced morphine-induced analgesia. These findings suggest that the NMDA antagonist, NPC 12626, may, either directly or indirectly, have effects on kappa opiate receptor mediated mechanisms.
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PMID:Antagonistic effects of the selective, competitive N-methyl-D-aspartate (NMDA) receptor antagonist, NPC 12626, on kappa opiate-induced analgesia in male deer mice. 818 Aug 9

Rats treated with an acute high dose (30 mg/kg) or 4 days with a lower dose (5 mg/kg) of naloxone or naltrexone show an analgesic response at the hot-plate test. This paradoxical analgesic effect of the two mu-opiate receptor antagonists is blocked by the kappa opiate receptor antagonist MR 1452, and is modulated by the kappa opiate receptor agonist U 50-488. Our results suggest that kappa opiate receptors are involved in naloxone-induced analgesia and are consistent with a high degree of plasticity of the opiatergic system.
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PMID:Naloxone-induced analgesia: involvement of kappa-opiate receptors. 825 4

The effects of endogenous opioid peptides are limited by proteolytic enzymes such as endopeptidase 24.11 ("enkephalinase"), which cleaves the Gly-Phe bonds in Met- and Leu-enkephalin. SCH 34826 [(S)-N-[n-[1-[(2,2-dimethyl-1,3-dioxolan-4- yl)methoxy]carbonyl]-2-phenylethyl]-L-phenyl-alanine-B-alanine] is a potent, highly specific, enkephalinase inhibitor that has marked analgesic effects in laboratory rodents. The present study compared the effects of SCH 34826 on nociception and restraint stress-induced opioid analgesia in reproductive adult male and female deer mice, Peromyscus maniculatus. SCH 34826 had significantly greater antinociceptive actions and facilitatory effects on stress-induced analgesia in male than female mice. These antinociceptive effects of SCH 34826 were reduced by the general opioid antagonist naloxone and completely blocked by the specific delta opioid receptor antagonist, ICI 174,864, and nonsignificantly affected by the mu and kappa opioid receptor antagonists, beta-funaltrexamine and nor-binaltorphimine, respectively. These results show that there are sex differences in the effects of the enkephalinase inhibitor, SCH 34826, on opioid-mediated antinociception and that these sex differences are associated with delta opioid mechanisms.
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PMID:Sex differences in the antinociceptive effects of the enkephalinase inhibitor, SCH 34826. 830 54

Morphine produces analgesia at opiate receptors expressed in nociceptive circuits. mu, delta, and kappa opiate receptor subtypes are expressed in circuits that can modulate nociception and receive inputs from endogenous opioid neuropeptide ligands. The roles played by each receptor subtype in nociceptive processing in drug-free and morphine-treated states have not been clear, however. We produced homologous, recombinant mu, opiate receptor, heterozygous and homozygous knockout animals that displayed approximately 54% and 0% of wild-type levels of mu receptor expression, respectively. These mice expressed kappa receptors and delta receptors at near wild-type levels. Untreated knockout mice displayed shorter latencies on tail flick and hot plate tests for spinal and supraspinal nociceptive responses than wild-type mice. These findings support a significant role for endogenous opioid-peptide interactions with mu opiate receptors in normal nociceptive processing. Morphine failed to significantly reduce nociceptive responses in hot plate or tail flick tests of homozygous mu receptor knockout mice, and heterozygote mice displayed right and downward shifts in morphine analgesia dose-effect relationships. These results implicate endogenous opioid-peptide actions at mu opiate receptors in several tests of nociceptive responsiveness and support mu receptor mediation of morphine-induced analgesia in tests of spinal and supraspinal analgesia.
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PMID:Opiate receptor knockout mice define mu receptor roles in endogenous nociceptive responses and morphine-induced analgesia. 903 90

Opioids administered by i.c.v. injection produce body temperature (Tb) changes and analgesic responses in rats. The present study was undertaken to investigate the effects on Tb and analgesia of highly selective mu and kappa opioid receptor agonists and antagonists delivered directly into the preoptic anterior hypothalamus (POAH) and periaqueductal gray (PAG) by the intracerebral microdialysis method. Microdialyzed into the POAH, the mu receptor agonist Tyr-Pro-N-MePhe-D-Pro-NH2 induced dose-related hyperthermia that could be prevented or antagonized by the mu receptor antagonist cyclic D-Phe-Cys-Tyr-D-Trp-Arg-Thr-Pen-Thr-NH2 or by naloxone, but not by the kappa receptor antagonist nor-binaltorphimine. The kappa receptor agonist dynorphin A(1-17), microdialyzed into the POAH, induced dose-related hypothermia that was prevented or antagonized by nor-binaltorphimine but not cyclic D-Phe-Cys-Tyr-D-Trp-Arg-Thr-Pen-Thr-NH2. Neither Tyr-Pro-N-MePhe-D-Pro-NH2 nor dynorphin A(1-17) microdialyzed into the PAG produced significant changes in Tb. However, these agonists microdialyzed into the PAG produced analgesic responses that did not occur after administration into the POAH. These results support the hypothesis that the hyperthermic response to opioids is mediated by the mu receptor and the hypothermic response is mediated by the kappa receptor in rats. The POAH is a primary functional area in Tb, but not in analgesic, responses to opioids, whereas the PAG is a sensitive area for analgesic, but not for Tb, responses to opioids.
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PMID:Body temperature and analgesic effects of selective mu and kappa opioid receptor agonists microdialyzed into rat brain. 910 37

Intracerebral microdialysis was used to measure changes in the extracellular level of substance P (SP) released from the periaqueductal gray (PAG) and the preoptic anterior hypothalamus (POAH) of freely moving Sprague-Dawley rats after noxious cold stimulation. Artificial cerebrospinal fluid was perfused into the dialysis probe in the PAG or POAH and samples were collected every 30 min for 4 hr. SP-like immunoreactivity in the samples was measured by radioimmunoassay. In the PAG, SP base-line release was 0.43 +/- 0.08 fmol/fraction. SP release was increased to 1.3 +/- 0.4 fmol/fraction during the first collection period after noxious cold. Pretreatment with the selective mu opioid receptor agonist PL017 (0.8-3.4 nmol) or the kappa opioid receptor agonist dynorphin A1-17 (4.6-9.2 nmol), administered into the PAG by microinjection, produced dose-related inhibition of the cold-evoked SP release. Naloxone (10 mg/kg s.c.) administration 10 min before these opioid agonists reduced the inhibition of SP release. In the POAH, SP base-line release was 0.45 +/- 0.06 fmol/fraction and noxious cold did not cause any significant change in SP release. Microdialysis of SP (271 fmol-271 pmol/microl/min, for 30 min) into the PAG, but not the POAH, induced dose-related analgesia (35-68% MPA) in the cold-water tail-flick test. However, microdialysis of SP into the POAH or PAG failed to induce any significant change in body temperature. These data suggest that 1) SP released from the PAG acts as a neuromodulator to transmit nociceptive information; 2) opioid receptor agonists can suppress this information by inhibiting SP release; 3) SP evoked by noxious cold may have a role in triggering the antinociceptive function of the PAG; and 4) SP does not appear to act as a neuromodulator for thermoregulatory responses in the POAH.
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PMID:Substance P release in the rat periaqueductal gray and preoptic anterior hypothalamus after noxious cold stimulation: effect of selective mu and kappa opioid agonists. 926 75

Research has demonstrated that intake of palatable carbohydrates and fats enhanced morphine-induced analgesia (MIA) in Sprague-Dawley rats. To determine if the effects of palatable foods on nociceptive responses would generalize to other strains of animals and other opioid agonists, the present experiments investigated whether intake of palatable foods would: a) alter MIA in Long-Evans rats, and b) alter analgesia produced by drugs acting at kappa opioid receptors. In experiment 1, adult male Long-Evans rats were fed Purina chow alone or chow and either a 32% sucrose solution, a 0.15% saccharin solution, or hydrogenated vegetable fat. Using a tail-flick apparatus, nociceptive responses, measured as percent maximal possible effect (%MPE), were examined after morphine administration [0.0, 1.0, 3.0, and 6.0 mg/kg subcutaneously (SC)]. %MPEs varied directly as a function of dose and were significantly greater for rats fed chow and either sucrose or fat than for rats fed chow alone or chow and saccharin. Experiment 2 compared the analgesic effect of the kappa opioid receptor agonist U50,488H (0, 5.0, 10.0, and 20.0 mg/kg SC) in rats fed chow alone or chow and a 32% sucrose solution. Administration of U50,488H led to analgesia. However, %MPEs did not vary directly as a function of dose. %MPEs of rats fed chow and sucrose were significantly greater than those of rats fed chow alone after injections of 10.0 and 20.0 mg/kg U50,488H. Experiment 3 compared the analgesic effect of U50,488H (5.0, 10.0, 15.0, and 20.0 mg/kg SC) in rats fed chow alone or chow and either a 0.15% saccharin solution or hydrogenated vegetable fat. Administration of U50,488H led to analgesia. However, %MPEs did not vary directly as a function of dose or as a function of diet. %MPEs of rats fed chow and fat were significantly greater than those of rats fed chow alone after injection of 5.0 mg/kg U50,488H.
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PMID:Dietary modulation of mu and kappa opioid receptor-mediated analgesia. 926 68

Fedotozine is a kappa opioid receptor agonist having antinociceptive properties but devoid of diuretic effects. The aim of the study was to evaluate the discriminative stimulus effects of fedotozine at doses previously reported to produce maximal effects in in vivo assays measuring kappa-mediated analgesia. By using a two-lever drug discrimination task, two groups of rats were trained to discriminate either a 3 mg/kg i.p. dose of the kappa opioid agonist, U50,488, or a 5 mg/kg i.p. dose of the mu opioid agonist, morphine, from saline. Once trained, rats were used to conduct tests of stimulus generalization with morphine, U50,488 and fedotozine along with another kappa agonist, CI-977, and another mu agonist, fentanyl. The stimulus effect of U50,488 was shared by CI-977 but not by morphine. Conversely, the stimulus effect of morphine was shared by fentanyl but not by U50,488. Fedotozine (1-10 mg/kg) failed to substitute to either U50,488 or morphine. These results indicate that, when administered at doses fully effective in producing antinociception, the interoceptive stimulus effects of fedotozine, if any, can be distinguished from those produced by U50,488 and morphine.
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PMID:The discriminative stimulus properties of U50,488 and morphine are not shared by fedotozine. 992 14

With the development of cDNA cloning technique in molecular biology, the research of opioids and opioid receptor as well as the mechanism of peripheral analgesia have made a great progress in the fields of receptor researches including molecular structure, morphology, molecular pharmacology, ion channel and intercellular signal transduction systems. The functional properties of mu, delta and kappa opioid receptor were determined by their structures. Depending on different proportional distribution in the primary sensory neurons, opioid receptor activation increases or decreases the potassium current and inhibits the calcium channel. There are different second message systems which are involved in the signal transduction between opioid receptors and ion channels. In addition, pharmacological evidence has also proved the existence of sub-types of opioid receptor, and the activation of these receptors can inhibit transmitters release from primary sensory neuron directly, which may be an important mechanism that opioid receptor has an analgesic effect in the peripheral nervous system.
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PMID:[Advances in the research of opioid receptor and ion channels of dorsal root ganglion neurons]. 1103 80


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