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)

Administration of cholecystokinin was recently found to attenuate opiate analgesia. In the present study, the role of endogenous cholecystokinin in opiate analgesia was examined. Endogenously released cholecystokinin was sequestered by antibodies to cholecystokinin developed in response to an active immunization procedure. Morphine analgesia was potentiated and prolonged in rats immunized against cholecystokinin. The rate of development of morphine tolerance, however, was not affected by the antibodies. Endogenous cholecystokinin appears to function as a short-term modulator of opiate action.
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PMID:Morphine analgesia potentiated but tolerance not affected by active immunization against cholecystokinin. 650 89

Exogenous cholecystokinin selectively antagonizes opiate analgesia, which suggests that endogenous cholecystokinin may act physiologically as an opiate antagonist and may play a role in opiate tolerance. The use of the selective cholecystokinin antagonist proglumide provided a test of these hypotheses in rats that were either inexperienced with or tolerant to opiates. Proglumide potentiated analgesia produced by morphine and endogenous opiates and seemed to reverse tolerance. These results suggest that endogenous cholecystokinin systems oppose the action of opiates.
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PMID:Potentiation of opiate analgesia and apparent reversal of morphine tolerance by proglumide. 654 9

The cholecystokinin (CCK) and gastrin families of peptides act as hormones and neuropeptides on central and peripheral CCK receptors to mediate secretion and motility in the gastrointestinal (GI) tract in the physiological response to a normal meal. CCK and its receptors are also widely distributed in the central nervous system (CNS) and contribute to the regulation of satiety, anxiety, analgesia, and dopamine-mediated behavior. Although the wide distribution, myriad number of functions, and reported pharmacological heterogeneity of CCK receptors would suggest a large number of receptor subtypes, the application of modern molecular biological techniques has identified two CCK receptors, CCK-A receptor (CCK-AR) and CCK-B receptor (CCK-BR), that mediate the actions of CCK and gastrin; gastrin receptors have been found to be identical to CCK-BR. CCK-AR, found predominantly in the GI system and select areas of the CNS, have high affinity for CCK and the nonpeptide antagonist L-364,718, whereas CCK-BR, found predominantly in the CNS and select areas of the GI system, have high affinity for CCK and gastrin and the nonpeptide antagonist L-365,260. Both CCK-AR and CCK-BR are highly conserved between species, although there is some tissue-specific variation in expression. Recombinant receptor expression faithfully reproduces the native receptor pharmacology and signal transduction pathways, allowing direct comparisons of receptor function between species as well as serving as a convenient source of receptor. Our present knowledge of the chromosomal localization, receptor gene structure, and primary sequence will allow further studies in disease association, receptor regulation, and structure-function analysis.
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PMID:Cholecystokinin receptors. 749 53

Male Wistar rats were treated with pethidine (PT) or fentanyl (FN) subcutaneously (sc) followed by intrathecal (ith) non analgesic doses of methionine- (MENK) or leucine-enkephalin (LENK), neurotensin, (NT), substance P (SP) or cholecystokinin octapeptide 26-33 (CCK-8). Then the antinociceptive effect was measured during 1 h using tail-immersion test. LENK potentiated strongly PT and FN analgesia. MENK antagonized PT analgesia only transiently 30 min after administration and transiently potentiated FN analgesia. SP and CCK-8 potentiated significantly PT analgesia, whereas NT acted biphasically: increasing and then decreasing PT analgesia. SP, CCK-8 and NT augmented FN analgesia. Naloxone inhibited analgesia elicited by the studied opioids and neuropeptides. These data show that LENK affects similarly the analgesic effects of both studied opioids, whereas MENK acted differently on PT and FN analgesia. This may suggest that individual enkephalins have different pharmacological features when interacting with different analgesics. Also NT interacted differently with pethidine and fentanyl.
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PMID:Pharmacological interaction between neuropeptides and pethidine or fentanyl in rat spinal cord. 751 84

Until recently, basic science studies, both behavioural and electrophysiological, have concentrated on the antinociceptive actions of opioids primarily gauged against acute nociceptive responses. However, of more relevance to clinical situations are the actions of opioids in more persistent/prolonged pain states. This review sets out to examine the central actions of opioids against nociception of inflammatory origins. The first section deals with the response of the endogenous opioid system to the development of an inflammatory state and the second examines the ability of exogenous opioids to modulate inflammatory nociception. There are complex changes in the roles of endogenous opioids, in particular dynorphin, at the spinal level after inflammation although the physiological consequences remain unclear. With regard to exogenous opioids, the effectiveness of spinal morphine is rapidly enhanced after inflammation, likely to be due to changes in the interaction between the peptide cholecystokinin and the mu opioid receptor. The ability of inflammatory processes to alter both endogenous opioids and morphine analgesia at the spinal level illustrates the considerable degree of plasticity observed in opioid function.
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PMID:Spinal opioid systems in inflammation. 758 17

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

Previous studies have established that the antinociceptive effect of morphine was subjected to peptidergic modulation at spinal level. Intrathecal (i.t.) galanin (GAL) potentiated morphine-induced analgesia, whereas i.t. cholecystokinin (CCK) antagonized morphine's hypoalgesic effect. In the present study, we examined the possible interaction between GAL, CCK and clonidine, an alpha 2 adrenoceptor agonist and potent spinal antinociceptive agent, in the spinal nociceptive flexor reflex. I.t. clonidine dose-dependently depressed the flexor reflex similarly to i.t. morphine. However, unlike morphine, the reflex depressive effect of i.t. clonidine was neither potentiated by i.t. GAL nor blocked by i.t. CCK. The present results suggested that the analgesia elicited by activation of spinal alpha 2 adrenoceptors is not subjected to the modulatory effect of CCK and GAL and therefore may be mediated through different mechanisms than opioids.
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PMID:Neither cholecystokinin nor galanin modulate intrathecal clonidine-induced depression of the nociceptive flexor reflex in the rat. 769 63

The endogenous peptides enkephalins and cholecystokinin appear to play an opposite role in the control of pain. In this work, the effect of the selective CCKB receptor antagonist PD-134,308 on antinociceptive effects induced by morphine or by a complete inhibitor of enkephalin-metabolizing enzymes, RB 101, was studied using the formalin test. In mice, s.c. injection of formalin into the dorsal surface of the hindpaw had a biphasic effect: an early nociceptive response followed by a late response. Morphine (2 mg/kg i.p.) caused naloxone (0.5 mg/kg s.c.) but not naltrindole (0.5 mg/kg s.c.) reversible antinociceptive responses in the early and late phases of the assay, suggesting a preferential involvement of mu-opioid receptors in these responses. In contrast, RB 101 (50 mg/kg i.p.) produced antinociceptive effects in the early and late phases which were both antagonized by the delta-selective opioid receptor antagonist naltrindole (0.5 mg/kg s.c.). The antinociceptive response elicited by morphine on the late but not the early phase of the formalin test was potentiated by the CCKB antagonist PD-134,308 (1 mg/kg i.p.). This compound was unable to facilitate the analgesic effects produced by RB 101 on both phases, in contrast to what was observed in the hot plate test with mice and the tail flick test with rats. Therefore, in the formalin test with mice, the facilitating effects of opiate-induced analgesia by CCKB receptor antagonists seem to be restricted to mu-opioid receptor-mediated responses.
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PMID:A selective CCKB receptor antagonist potentiates, mu-, but not delta-opioid receptor-mediated antinociception in the formalin test. 773 8

The analgesic effect of systemic morphine (4 mg/kg, s.c.) was antagonized in a dose-dependent manner by cholecystokinin octapeptide (CCK-8) (0.1-0.5 ng) administered bilaterally to the nucleus accumbens of the rat. This effect of CCK-8 could be reversed by devazepide, a CCK-A receptor antagonist, at 50 ng and 200 ng and by L-365,260, a CCK-B receptor antagonist, at 5 ng administered bilaterally to the nucleus accumbens. A marked potentiation of morphine analgesia was achieved by intra-nucleus accumbens injection of 200 ng devazepide or 5 ng L-365,260. Since the effect of L-365,260 in antagonizing the anti-opioid effect of CCK-8 in the nucleus accumbens is 40 times more potent than devazepide, it is suggested that the anti-opioid effect of CCK-8 is mediated by CCK-B receptors. In conclusion, nucleus accumbens is a strategic site where CCK-8 exerts an anti-opioid activity, most probably via the CCK-B receptors.
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PMID:Cholecystokinin octapeptide (CCK-8) antagonizes morphine analgesia in nucleus accumbens of the rat via the CCK-B receptor. 782 Jun 14

Cholecystokinin (CCK) has been shown to reduce the spinal antinociceptive effects of opioid agonists such as morphine. The present study examined the effect of CCK and CCKB antagonists on the spinal antinociception mediated by the selective alpha 2-adrenergic agonist dexmedetomidine. Extracellular recordings of noxious-evoked C fibre responses of dorsal horn convergent neurones were made in the halothane-anaesthetized rat. Alone, intrathecal dexmedetomidine (5 micrograms) profoundly inhibited C fibre-evoked responses (92 +/- 7%). In the presence of 1 microgram intrathecal CCK the antinociceptive effect of dexmedetomidine was reduced to 27 +/- 11%. Inhibitions of C fibre-evoked responses mediated by submaximal doses (0.5 and 2.5 micrograms) dexmedetomidine were not altered by CCKB antagonists L365,260 (0.2 mg/kg subcutaneous) or PD135158 (10 micrograms intrathecal). Both CCKB antagonists did increase the inhibition of C fibre-evoked responses by the mu opioid agonists DAGOL and morphine. The results suggest CCK is able to inhibit spinal antinociception mediated via the activation of alpha 2-adrenergic receptors in addition to its well-documented interaction with spinal opioid analgesia. However the antagonist studies indicate an endogenous CCK control of spinal mu opioid mediated antinociception which does not extend to alpha 2-adrenergic antinociception.
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PMID:Differential modulation of alpha 2-adrenergic and opioid spinal antinociception by cholecystokinin and cholecystokinin antagonists in the rat dorsal horn: an electrophysiological study. 785 67


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