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)

The activation of intracerebral corticotropin releasing factor (CRF) system is involved in nitrous oxide analgesia. We evaluated the effect of general anesthetics on nitrous-oxide-induced CRF activation and antinociception. Male Sprague-Dawley rats inhaled isoflurane (0%, 0.6%, 1.0% and 1.5%) or were administered with intravenous propofol (0, 0.1 and 0.2 mg/kg/min), with or without 75% nitrous oxide inhalation, for 90 min. The brain was fixed with fixative, and brain sections, including the paraventricular nucleus of the hypothalamus, were double immunostained with c-Fos and CRF antibodies to assess the activation of CRF-containing neurons. In other groups of rats, the effect of propofol on nitrous oxide antinociception was evaluated with tail flick latency tests. Both inhaled isoflurane and intravenous propofol inhibited nitrous-oxide-induced activation of CRF neurons, suggesting that these general anesthetics may inhibit one of the analgesic mechanisms of nitrous oxide. Indeed, propofol inhibited the antinociceptive action of nitrous oxide, as evaluated with tail flick latencies (TFL).
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PMID:General anesthetics inhibit the nitrous-oxide-induced activation of corticotropin releasing factor containing neurons in rats. 1549 95

When tissue is destroyed or invaded by leukocytes in inflammation, numerous mediators are delivered by the circulation and/or liberated from resident and immigrated cells at the site. Proalgesic mediators include proinflammatory cytokines, chemokines, protons, nerve growth factor, and prostaglandins, which are produced by invading leukocytes or by resident cells. Less well known is that analgesic mediators, which counteract pain, are also produced in inflamed tissues. These include anti-inflammatory cytokines and opioid peptides. Interactions between leukocyte-derived opioid peptides and opioid receptors can lead to potent, clinically relevant inhibition of pain (analgesia). Opioid receptors are present on peripheral endings of sensory neurons. Opioid peptides are synthesized in circulating leukocytes, which migrate to inflamed tissues directed by chemokines and adhesion molecules. Under stressful conditions or in response to releasing agents (e.g., corticotropin-releasing factor, cytokines, noradrenaline), leukocytes can secrete opioids. They activate peripheral opioid receptors and produce analgesia by inhibiting the excitability of sensory nerves and/or the release of excitatory neuropeptides. This review presents discoveries that led to the concepts of pain generation by mediators secreted from leukocytes and of analgesia by immune-derived opioids.
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PMID:Leukocytes in the regulation of pain and analgesia. 1620 36

Corticotropin-releasing factor (CRF) and urocortin 1 (Ucn1) are involved in stress adaptation. CRF receptor 1 (CRF1) binds CRF and Ucn1 with similar high affinity, but CRF receptor 2 (CRF2) binds Ucn1 with higher affinity than CRF. We tested the hypothesis that in the spinal cord CRF and Ucn1 control peripheral components of the stress response, by assessing the distribution of CRF- and Ucn1-containing fibers, CRF1 and CRF2 mRNAs, and CRF receptor protein (CRFR) in the mouse spinal cord, by using immunofluorescence and in situ hybridization. CRF, Ucn1, and CRFR occurred throughout the spinal cord. CRF fibers predominated in laminae I, V-VII, and X of Rexed. Ucn1 fibers occurred mainly in laminae VII and X and occasionally in lamina IX. Both CRFR mRNAs occurred in all laminae except the superficial laminae of the dorsal horn, but they exhibited different distributions, CRF2 mRNA having a wider occurrence (laminae III-X) than CRF1 mRNA (laminae III-VIII). Double immunofluorescence indicated that CRF and Ucn1 fibers contacted CRFR-containing neurons, mainly in laminae VII and X. The strongest co-distribution of CRF1 and CRF2 mRNAs with CRF and Ucn1 fibers appeared in lamina VII. CRF2 mRNA predominated in lamina IX together with Ucn1, whereas CRF2 mRNA predominated in lamina X, where it had similar distributions with each ligand. In view of the lamina-specific and similar distributions of the two CRF receptor mRNAs with their ligands, we suggest that CRF1 and CRF2 are involved in peripheral stress adaptation processes, such as modulation of stress-induced analgesia and the mediation of visceral nociceptive information by CRF2.
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PMID:Corticotropin-releasing factor, urocortin 1, and their receptors in the mouse spinal cord. 1744 96

It is accepted that inflammatory mediators released from leukocytes contribute to the generation of pain. However, it is less well known that immune cells also produce mediators that can effectively counteract pain. These include anti-inflammatory cytokines and opioid peptides. This article concentrates on recent evidence that interactions between leukocyte-derived opioid peptides and their receptors on peripheral sensory neurons can result in potent, clinically relevant inhibition of pathological pain. Inflammation of peripheral tissues leads to increased synthesis and axonal transport of opioid receptors in dorsal root ganglion neurons. This results in opioid receptor upregulation and enhanced G-protein coupling at peripheral sensory nerve terminals. These events are dependent on neuronal electrical activity, production of proinflammatory cytokines and nerve growth factor within the inflamed tissue. Together with the disruption of the perineurial barrier, all these changes lead to an enhanced peripheral analgesic efficacy of opioids. The major source of local endogenous opioid ligands (beta-endorphin, enkephalins, endomorphins and dynorphin) are leukocytes. These cells contain and upregulate signal-sequence encoding mRNA of the beta-endorphin precursor proopiomelanocortin and the entire enzymatic machinery necessary for its processing into the functionally active peptide. Opioid-containing immune cells extravasate using adhesion molecules and chemokines to accumulate in inflamed tissues. Upon stressful stimuli or in response to releasing agents such as corticotropin-releasing factor, cytokines, chemokines and catecholamines, leukocytes secrete opioids. Depending on the cell type, this release is contingent on extracellular Ca(2+) or on inositol triphosphate receptor-triggered release of Ca(2+) from endoplasmic reticulum. Once secreted opioid peptides activate peripheral opioid receptors and produce analgesia by inhibiting the excitability of sensory nerves and/or the release of excitatory neuropeptides. These effects occur without central untoward side effects such as depression of breathing, clouding of consciousness or addiction. Future aims include the selective targeting of opioid-containing leukocytes to sites of painful injury and the augmentation of opioid peptide and receptor synthesis.
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PMID:Targeting of opioid-producing leukocytes for pain control. 1764 Jul 27

In peripheral inflamed tissue interactions between leukocyte-derived opioid peptides and opioid receptors on sensory neurons lead to potent, clinically relevant inhibition of pain. Opioid receptors are present on peripheral terminals of sensory neurons and are upregulated in inflammation. Their endogenous ligands, opioid peptides, are synthesized in circulating immune cells, which migrate to injured tissues directed by chemokines and adhesion molecules. Under stressful stimuli or in response to releasing agents (e.g., corticotropin-releasing factor, cytokines, catecholamines) leukocytes can secrete opioids. These peptides activate peripheral opioid receptors and produce analgesia by inhibiting the excitability of sensory nerves and/or the release of excitatory neuropeptides. These effects occur without central opioid side effects such as depression of breathing, clouding of consciousness, or addiction. Future research should elucidate the selective targeting of opioid peptide-containing immune cells to sites of painful tissue injury and the augmentation of opioid peptide and receptor synthesis.
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PMID:Leukocyte-derived opioid peptides and inhibition of pain. 1804 Jul 94

In inflammation, resident cells and infiltrating leukocytes produce proalgesic mediators. Although these mediators induce pain, the role of specific cell populations is still controversial. In addition, resident cells and leukocytes also generate analgesic mediators that counteract inflammatory pain, including anti-inflammatory cytokines, endocannabinoids, and opioid peptides. Chemokines and adhesion molecules orchestrate the migration of opioid peptide-containing leukocytes to inflamed tissue. Leukocytes secrete opioid peptides under stressful conditions or in response to releasing agents (eg, corticotropin-releasing factor and chemokines). Secretion requires intracellular calcium mobilization and activation of phosphinositol-3 kinase and p38 mitogen activated kinase. Following release, opioid peptides bind to receptors on peripheral sensory neurons and produce analgesia in animal models and humans. This review presents recent findings on the role of leukocytes in the generation and inhibition of inflammatory pain.
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PMID:Leukocytes as mediators of pain and analgesia. 1817 5

Stress-induced analgesia (SIA) is a key component of the defensive behavioral "fight-or-flight" response. Although the neural substrates of SIA are incompletely understood, previous studies have implicated the hypocretin/orexin (Hcrt) and nociceptin/orphanin FQ (N/OFQ) peptidergic systems in the regulation of SIA. Using immunohistochemistry in brain tissue from wild-type mice, we identified N/OFQ-containing fibers forming synaptic contacts with Hcrt neurons at both the light and electron microscopic levels. Patch clamp recordings in GFP-tagged mouse Hcrt neurons revealed that N/OFQ hyperpolarized, decreased input resistance, and blocked the firing of action potentials in Hcrt neurons. N/OFQ postsynaptic effects were consistent with opening of a G protein-regulated inwardly rectifying K+ (GIRK) channel. N/OFQ also modulated presynaptic release of GABA and glutamate onto Hcrt neurons in mouse hypothalamic slices. Orexin/ataxin-3 mice, in which the Hcrt neurons degenerate, did not exhibit SIA, although analgesia was induced by i.c.v. administration of Hcrt-1. N/OFQ blocked SIA in wild-type mice, while coadministration of Hcrt-1 overcame N/OFQ inhibition of SIA. These results establish what is, to our knowledge, a novel interaction between the N/OFQ and Hcrt systems in which the corticotropin-releasing factor and N/OFQ systems coordinately modulate the Hcrt neurons to regulate SIA.
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PMID:Hypocretin/orexin and nociceptin/orphanin FQ coordinately regulate analgesia in a mouse model of stress-induced analgesia. 1855 Nov 94

The aim of this study was to investigate the participation of glucocorticoid receptors and corticotropin releasing factor receptors of subtype 2 (CRF-2 receptors) in the analgesic effect of CRF on somatic pain sensitivity. The participation of glucocorticoid receptors and CRF-2 receptors in the CRF-induced analgesia was investigated by the receptors antagonists: RU38486 or astressin 2-B, respectively, in anaesthetized rats. For estimation of pain sensitivity the threshold of pain reaction induced by electrical stimulation of the rat' tail as tested before and during 30 min after the systemic injection of CRF. The CRF-induced analgesic effect was partly abolished by glucocorticoid receptor antagonist RU 38486 and completely abolished by CRF-2 receptor antagonist astressin 2-B. The data suggest that glucocorticoid receptors and CRF-2 receptors participate in the CRF-induced analgesic effect.
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PMID:[Analgesic effect of corticotropin releasing factor (CRF) on somatic pain sensitivity: participation of glucocorticoid and CRF-2 receptors]. 1906 25

This chapter reviews the expression and regulation of opioid receptors in sensory neurons and the interactions of these receptors with endogenous and exogenous opioid ligands. Inflammation of peripheral tissues leads to increased synthesis and axonal transport of opioid receptors in dorsal root ganglion neurons. This results in opioid receptor upregulation and enhanced G protein coupling at peripheral sensory nerve terminals. These events are dependent on neuronal electrical activity, and on production of proinflammatory cytokines and nerve growth factor within the inflamed tissue. Together with the disruption of the perineurial barrier, these factors lead to an enhanced analgesic efficacy of peripherally active opioids. The major local source of endogenous opioid ligands (e.g. beta-endorphin) is leukocytes. These cells contain and upregulate signal-sequence-encoding messenger RNA of the beta-endorphin precursor proopiomelanocortin and the entire enzymatic machinery necessary for its processing into the functionally active peptide. Opioid-containing immune cells extravasate using adhesion molecules and chemokines to accumulate in inflamed tissues. Upon stressful stimuli or in response to releasing agents such as corticotropin-releasing factor, cytokines, chemokines, and catecholamines, leukocytes secrete opioids. Depending on the cell type, this release is contingent on extracellular Ca(2+) or on inositol triphosphate receptor triggered release of Ca(2+) from endoplasmic reticulum. Once secreted, opioid peptides activate peripheral opioid receptors and produce analgesia by inhibiting the excitability of sensory nerves and/or the release of proinflammatory neuropeptides. These effects occur without central untoward side effects such as depression of breathing, clouding of consciousness, or addiction. Future aims include the development of peripherally restricted opioid agonists, selective targeting of opioid-containing leukocytes to sites of painful injury, and the augmentation of peripheral opioid peptide and receptor synthesis.
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PMID:Opioids and sensory nerves. 1965 16

The aim of the present work was to study the involvement of glucocorticoid receptors and corticotropin-releasing factor type 2 receptors (CRF-2 receptors) in mediating the analgesic effects of CRF on somatic pain sensitivity. The involvement of glucocorticoid and CRF-2 receptors in the development of analgesia evoked by systemic administration of CRF was studied by blockade of these receptors by their specific antagonists RU 38486 and astressin 2-B, respectively, in anesthetized rats. Pain sensitivity was tested before and 30 min after administration of CRF in terms of the threshold of the pain reaction induced by stimulation of the rat's tail with an electric current. Blockade of glucocorticoid receptors induced partial suppression of the analgesic action of CRF, while blockade of CRF-2 receptors produced complete suppression of the analgesic effect. These results provide evidence that glucocorticoid and CRF-2 receptors are involved in mediating the analgesic effects of CRF.
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PMID:Analgesic actions of corticotropin-releasing factor (CRF) on somatic pain sensitivity: involvement of glucocorticoid and CRF-2 receptors. 1983 May 68


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