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)

We have previously shown that norepinephrine can produce hyperalgesia via an alpha 2-adrenergic receptor mechanism. The alpha 2-adrenergic receptor agonist clonidine has, however, also been shown to produce peripheral analgesia. In view of the multiple alpha 2-subtypes currently known (i.e. alpha 2A, alpha 2B and alpha 2C), we evaluate the alpha 2-receptor subtypes mediating norepinephrine-induced peripheral hyperalgesia and clonidine analgesia. Norepinephrine and the alpha 2-adrenergic agonists clonidine and UK 14,304 (1-1000 ng), when co-injected with the calcium ionophore A23187 (1000 ng) produced dose-dependent hyperalgesia in the Randall-Selitto paw withdrawal test. Norepinephrine (100 ng) hyperalgesia was dose-dependently antagonized by alpha 2-adrenergic receptor antagonists. From the estimated ID50, the rank order of potency was: SK&F 104856 (alpha 2B) approximately imiloxan (alpha 2B) > rauwolscine (alpha 2C) >> BRL 44408 (alpha 2A). Norepinephrine hyperalgesia was not significantly affected by pertussis-toxin treatment. Prostaglandin E2 (100 ng) hyperalgesia was inhibited dose-dependently, by clonidine and UK 14,304. Rauwolscine was more potent in reversing the inhibitory effect of clonidine on prostaglandin E2 than imiloxan while BRL 44408 was ineffective. The inhibitory effect of clonidine on prostaglandin E2 hyperalgesia was reversed by pertussis toxin. These data suggest that alpha 2B-subtype receptors mediate (norepinephrine hyperalgesia while the antinociceptive effect of alpha 2-agonist is mediated by the alpha 2C-subtype receptor. Differential coupling of these receptor subtypes to second messenger systems and location on different cell types in the rat paw may explain, at least in part, their differential responses to alpha 2-agonist stimulation, leading to hyperalgesia and analgesia.
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PMID:Peripheral nociceptive effects of alpha 2-adrenergic receptor agonists in the rat. 747 83

Opioid analgesia, the selective suppression of pain without effects on other sensations, also distinguishes between different types of pain: severe, persistent pain is potently inhibited by opioids, but they fail to cohceal the sensation of a pinprick. The cellular basis for this specificity was analyzed by means of patch-clamp experiments performed on fluorescently labeled nociceptive neurons (nociceptors) that innervate rat tooth pulp. Activation of the mu opioid receptor inhibited calcium channels on almost all small nociceptors but had minimal effect on large nociceptors. Somatostatin had the opposite specificity, preferentially inhibiting calcium channels on the large cells. Because persistent pain is mediated by slow-conducting, small nociceptors, opioids are thus likely to inhibit neurotransmitter release only at those primary synapses specialized for persistent pain.
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PMID:Selective opioid inhibition of small nociceptive neurons. 748 26

We investigate the modulatory effects of subcutaneous administration of different doses of KB-2796 (1, 5 and 15 mg/kg), a new calcium channel blocker, and BAY K 8644 (0.25, 0.5 and 1 mg/kg), a calcium agonist, on fentanyl-induced analgesia (20 micrograms/kg) in rats. The drugs were tested individually as well as in combination with fentanyl. Dimethyl sulfoxide (DMSO) was used as a control. Nociceptive sensitivity was assessed by the tail-flick technique. When KB-2796 and BAY K 8644 were used alone, only KB-2796 at the dose of 15 mg/kg produced an effect that was significantly different from that of DMSO (p < 0.01). The effect was antinociceptive. When administered with fentanyl, KB-2796 at 5 and 15 mg/kg potentiated the analgesic effect of fentanyl (p < 0.05), but suppression of fentanyl analgesia by BAY K 8644 was not significant at any of the doses tested. Our data supports the hypothesis that the calcium ion is partially involved in fentanyl-induced analgesia.
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PMID:The effects of KB-2796 and BAY K 8644 on fentanyl-induced analgesia in rats. 751 14

The aim of the present work was to clarify the role of calcium influx through L-type calcium channels in the rewarding and analgesic effects of morphine. Therefore the effects of Bay K-8644 and nimodipine, dihydropyridine calcium agonist and antagonist, respectively, on the analgesic and rewarding effects of morphine in mice were studied. Morphine-induced analgesia was measured with the aid of writhing test, hot plate test and tail clip test. The rewarding properties of morphine were studied using i.v. self-administration in drug-naive mice. Bay K-8644 potentiated morphine-induced analgesia in all the tests. The influence of nimodipine on morphine analgesia was more complicated and depended on the dose of morphine and test used. In self-administration experiments morphine exhibited the bell-shaped concentration-response curve. Bay K-8644 produced a shift of the curve to the left, while nimodipine had the opposite action indicating, respectively, facilitating and inhibitory influence on morphine rewarding effect. It is concluded that nimodipine exhibits partial antagonistic properties towards the rewarding action of morphine and slightly potentiates morphine-induced analgesia while Bay K-8644 increases either the rewarding or the analgesic effects of morphine.
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PMID:Analgesic and reinforcing effects of morphine in mice. Influence of Bay K-8644 and nimodipine. 752 18

The purpose of this investigation was to determine if analogous to (-)-nicotine's analgesic effect, the analgesic effect of the recently characterized potent nicotinic acetylcholine receptor (nAChR) agonist (+/-)-epibatidine was altered in response to treatment with the calcium channel agonist (+/-)-Bay K 8644. In addition, the effects of the enantiomers, (+)-Bay K 8644, reported to be a calcium channel antagonist, and (-)-Bay K 8644, reported to be a calcium channel agonist were examined. (+/-)-Bay K 8644 (2.8 mumol/kg; i.p.) produced a large analgesic response in mice in the hot-plate paradigm that rapidly dissipated by 30 min after treatment. This analgesic effect of (+/-)-Bay K 8644 was not prevented by pre-treatment with the nicotinic antagonist mecamylamine (5 mumol/kg; i.p.). Treatment with non-analgesic doses of the calcium channel agonists (+/-)- and (-)-Bay K 8644 (1.4 mumol/kg; i.p.) significantly potentiated the analgesic effect of (+/-)-epibatidine (0.05 mumol/kg; i.p.). Potentiation of (+/-)-epibatidine's analgesic effect occurred when the agonists were administered prior to (+/-)-epibatidine or after (+/-)-epibatidine as long as analgesia testing was conducted 15 to 30 min after Bay K 8644 treatment. Pre-treatment with the calcium channel antagonist (+)-Bay K 8644 was found to attenuate (+/-)-epibatidine-induced analgesia. When given after (+/-)-epibatidine, (+)-Bay K 8644 had no effect on (+/-)-epibatidine's analgesic effect. These data provide additional in vivo evidence that altering calcium dynamics can modulate neuronal nAChR function.
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PMID:The influence of Bay K 8644 treatment on (+/-)-epibatidine-induced analgesia. 754 42

Two subtypes of cannabinoid receptors, CB1 and CB2, have been described to date, although future investigations may elucidate other receptors. The actions of cannabimimetic agents via CB1 receptors in brain are mediated by GI/O to inhibit adenylate cyclase and Ca2+ channels. Little is known about signal transduction mechanisms utilized by CB2 receptors. Three classes of agonist ligands regulate cannabinoid receptors: cannabinoid, aminoalkyl-indole, and eicosanoid derivatives. Cannabinoid receptors produce analgesia and modify cognition, memory, locomotor activity, and endocrine functions in mammals.
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PMID:Pharmacology of cannabinoid receptors. 759 9

Using the behavioral pharmacological approach, we have studied the influence of ACTH on the analgesia mediated by three types of opioid receptors (mu, delta, kappa). The mechanisms by which ACTH antagonizes opioid analgesia were explored at receptor level and post-receptor second messenger level. The expression of Fos protein induced by ACTH was also observed in rat brain. The main results show that ACTH selectively antagonizes spinal opioid analgesia mediated by mu and delta, but not kappa receptors. The proposed mechanisms of the anti-opioid effect of ACTH are that ACTH can modulate opioid-induced decrease of intracellular cAMP content and the suppression of calcium influx. ACTH has been shown to induce Fos protein expression in selected brain areas including the nuclei involved in pain modulation. These brain areas may serve as sites of action for ACTH to exert its anti-opioid effect.
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PMID:[Adrenocorticotropic hormone (ACTH): antagonistic effect on opioid analgesia in central nervous system of the rat and its possible mechanisms of action]. 765 13

Activation of the endogenous opioid system can suppress pain without affecting other sensations, but the cellular mechanism of this selectivity is unclear. The analgesia might be due to inhibitory synapses arranged only on neurons whose activity leads to pain sensations. Alternatively, opioids might be released broadly, with neurons involved in pain sensation being especially sensitive. Therefore, we asked whether different subsets of rat dorsal root ganglion (DRG) sensory neurons vary in their sensitivity to opioids. Dissociated neurons were subdivided according to the spinal laminae to which they likely had projected, and whether they had innervated muscle. Using the patch-clamp method, we measured the inhibition of Ca2+ current by DAGO (Tyr-D-Ala-Gly-MePhe-Gly-ol), a peptide that selectively activates the mu (morphine) receptor. We also investigated the presence of different types of Ca2+ channels. In DRG neurons chosen at random, Ca2+ currents were inhibited by DAGO to widely varying degrees, with an average inhibition of 38%. Ca2+ currents in neurons in a subset that projects to laminae I and II had a lower average inhibition, and unlike the randomly selected cells, the responses were predictable and tightly distributed about the mean. This indicates that the variability of opioid sensitivity among DRG neurons reflects the presence of different subsets of cells. Since neurons projecting to laminae I and II, the projection site of nociceptive neurons, did not show high opioid sensitivity, there is no evidence that nociceptive neurons have stronger responses to opioids. But a firm conclusion is impossible because projection site does not strictly define sensory modality.
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PMID:Inhibition of Ca2+ currents by a mu-opioid in a defined subset of rat sensory neurons. 767 62

The predominant brain cholecystokinin receptor (CCK-B/gastrin) has been implicated in mediating many of the central effects of cholecystokinin, including anxiety, panic attacks, satiety, and analgesia, suggesting it is an important pharmacologic target. We now report the cloning and characterization of the cDNA encoding the human brain CCK-B/gastrin receptor. The cDNA was isolated from a human brain library by low stringency screening using the canine "gastrin" receptor cDNA as a hybridization probe. Nucleotide sequence analysis revealed an open reading frame encoding a 447-amino-acid protein with seven putative hydrophobic transmembrane domains and significant homology with other known members of the gastrin/cholecystokinin receptor family. Agonist and antagonist affinities of the recombinant human brain receptor expressed in COS-7 cells are consistent with a classical "CCK-B" receptor as defined by the literature. In COS-7 cells expressing the cloned receptor, CCK-8-stimulated phosphatidylinositol hydrolysis and intracellular Ca2+ mobilization suggesting second messenger signaling through phospholipase C. CCK-B/gastrin receptor transcripts were identified in human brain, stomach, and pancreas using high stringency Northern blot analysis. Southern blot hybridization analysis of human genomic DNA indicates that a single gene encodes both the brain and the stomach CCK-B/gastrin receptors. Our data suggest that the CCK-B and gastrin receptors are identical and that the long standing distinction between them may no longer apply.
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PMID:The human brain cholecystokinin-B/gastrin receptor. Cloning and characterization. 768 36

1. The effects of acute and chronic lithium (Li+) treatments on the antinociception caused by morphine were studied in mice using the tail-flick test. 2. Subcutaneous injection of morphine (10 mg/kg) caused significant antinociception. 3. Acute Li+ administration (0.05, 0.1, 0.3, 1, 5 and 10 mg/kg, i.p.) alone had no significant antinociceptive effect but changed morphine analgesia; low doses of Li+ (0.1, 0.3 and 1 mg/kg) were found to decrease the antinociception induced by morphine whereas higher doses of the drug (10 mg/kg) potentiated this effect. 4. The 6 day administration of Li+ with a serum level of 0.528 mM decreased the antinociceptive effect of morphine. 5. The effect of Li+ on morphine-induced analgesia persisted for 96 hr in spite of the fact that Li+ drinking was discontinued (the serum Li+ level decreased from 0.528 to 0.022 mM). 6. It has been reported that Li+ might change both the binding of opioids to their receptors and biosynthesis or release of endogenous opioids. There is also a considerable body of evidence which indicates that both Li+ and morphine affect phosphoinositide turnover, intracellular calcium content and cyclic AMP level. The interaction of two drugs may conceivably take place through these systems. 7. These data suggest that the biological effects of Li+ may exist at very much lower serum Li+ levels than the commonly accepted therapeutic range.
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PMID:The effect of lithium on morphine-induced analgesia in mice. 772 Oct 39


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