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)

Cholecystokinin octapeptide (CCK-8) and angiotensin I (AI) have been shown in behavioral studies being endogenous antiopioid substrates (AOS). To assess their antiopioid mechanism at postreceptor level, we observed the effects of the three opioids and the two AOS on 45Ca uptake of the rat spinal synaptosomal preparations. Morphine, Dyn A and DPDPE at concentrations of 10 nmol/L to 1 mumol/L, produced a mild suppression of 45Ca uptake of synaptosomal preparations from ventral spinal cord. CCK-8 showed a mild suppression only at a concentration of 1 mumol/L. In synaptosomes prepared from dorsal spinal cord, Dyn A but not morphine or DPDPE, produced a strong inhibition of 45Ca uptake which was blocked by nor-BNI, a kappa receptor antagonist, at 1 mumol/L. While CCK-8 (10 nmol/L to 1 mumol/L) also suppressed 45Ca uptake, it could antagonize the suppressive effect induced by Dyn A. In contrast to CCK-8, AI (10 nmol/L to 1 mumol/L) influenced neither on synaptosomal 45Ca uptake, nor on Dyn A suppression of 45Ca uptake. The results presented above fit very well with our behavioral studies, i.e., CCK-8 antagonized opioid analgesia in both the brain and the spinal cord, whereas AI antagonized opioid analgesia in the brain but not in the spinal cord. It is therefore concluded that antagonism of the opioid suppression of synaptosomal 45Ca uptake might be one of the mechanisms for the antiopioid activity of CCK-8 and AI.
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PMID:[Effects of dynorphin A and CCK-8 on synaptosomal 45Ca uptake of the rat spinal cord]. 198 24

Extracellular single unit recordings were made from dorsal horn nociceptive neurons of intact, urethane-anesthetized rats during controlled electrical stimulation of the hind paw. Neither local superfusion of cholecystokinin octapeptide (CCK; 6.4 pmol to 20 nmol) nor the CCK antagonist lorglumide (LGM; 145 fmol to 145 pmol) significantly altered A- or C-fiber evoked firing or spontaneous activity. Pretreatment with CCK, however, significantly attenuated, whereas LGM enhanced, morphine-induced inhibition of C-evoked firing. These findings provide further evidence that CCK functions as a selective antagonist of opioid-induced analgesia.
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PMID:Cholecystokinin and its antagonist lorglumide respectively attenuate and facilitate morphine-induced inhibition of C-fiber evoked discharges of dorsal horn nociceptive neurons. 205 23

Cholecystokinin-octapeptide (CCK-8) has been shown to antagonize the analgesia produced by opioid peptides. The present study was performed to evaluate its effect on cardiovascular regulatory functions of opioids. Both CCK-8 and opioid peptides were injected intrathecally (ith) in pentobarbital anaesthetized rats. The depressive effects induced by the mu agonist PL017 (5 micrograms), delta agonist DADLE (25 micrograms) and kappa agonist 66A-078 (1 microgram) were antagonized by CCK-8 within a dosage of 10 micrograms in a dose dependent manner. CCK-8 can also partly antagonize the bradycardiac effects induced by PL017, DADLE and 66A-078. The antagonistic effect of CCK-8 on DADLE in MAP could be reversed by pretreatment with CCK receptor antagonist proglumide (100 micrograms). No significant changes in MAP were found following ith administration of CCK-8 0.5-10 micrograms and proglumide 100 micrograms, but a large dose (50 micrograms) of CCK-8 lowered MAP dramatically. The results suggest that within a certain range of dose CCK-8 in spinal cord may play an antagonistic role against opioid effects in the regulation of cardiovascular function and this effect of CCK-8 seems to be mediated by CCK receptor. These results support the hypothesis that CCK-8 may act as an anti-opioid substance in the CNS of the rat.
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PMID:[Cholecystokinin-octapeptide antagonizes the central depressive effect of opioid peptides in rats]. 206 85

The potential antinociceptive effects of the selective cholecystokinin-B (CCK-B) antagonist L-365,260 were examined in the squirrel monkey tail withdrawal test. Pain threshold was measured in 6 male monkeys by recording the latency to remove the tail from a warm (55 degrees C) water bath. L-365,260 at doses of 100 ng/kg to 100 micrograms/kg significantly elevated tail withdrawal latencies throughout a 2 h test period. These data provide the first evidence that blockade of CCK-B receptors induces analgesia in primates.
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PMID:Blockade of CCK-B receptors by L-365,260 induces analgesia in the squirrel monkey. 207 89

The cholecystokinin antagonist proglumide potentiates morphine analgesia. To understand more fully the opiate receptor subtypes involved with this effect, we investigated the effect of proglumide on spinal and supraspinal mu and spinal delta analgesia in mice. Proglumide alone had no effect on tailflick latencies, but increased, in a dose-dependent manner, tailflick latencies in morphine-tolerant mice. Proglumide also potentiated morphine analgesia in naive mice in a dose-dependent manner, with a maximal effect at 5-10 mg/kg. Proglumide both shifted the dose-response curve for morphine analgesia to the left and prolonged morphine's duration of action. Proglumide increased the sensitivity of supraspinal mu 1 receptor mechanisms of analgesia without influencing spinal mechanisms. Proglumide administered subcutaneously potentiated the analgesic actions of intracerebroventricular [D-Ala2,MePhe4,Gly(ol)5]enkephalin (DAGO; (mu 1), but not intrathecal DAGO (mu 2) or [D-Pen2,D-Pen5]enkephalin (DPDPE; delta). The selective mu 1 receptor antagonist naloxonazine blocked proglumide-enhanced morphine analgesia.
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PMID:Proglumide selectively potentiates supraspinal mu 1 opioid analgesia in mice. 216 97

The effects of the cholecystokinin antagonist devazepide on analgesia and respiratory depression induced by morphine in squirrel monkeys were examined. Pain thresholds were determined using the tail withdrawal procedure, in which monkeys restrained in chairs kept their tails in cool (35 degrees C) water for at least 20 sec, but withdrew them from warm (55 degrees C) water in less than 4 sec. Morphine produced a dose-related increase in tail withdrawal latencies from warm water. Devazepide (injected i.p. or p.o.) had no effect on tail withdrawal latencies when given alone but enhanced the analgesic effects of morphine. The devazepide dose-response curve for morphine enhancement was bell-shaped with doses of 3, 10, 30 and 100 micrograms/kg injected i.p. increasing morphine analgesia whereas higher and lower dose did not. In a separate group of monkeys, morphine produced dose-dependent decreases in respiratory rate and oxygen tension and increases in carbon dioxide tension. In contrast to its effects on morphine analgesia, devazepide had no effect on the various indices of morphine-induced respiratory depression. These data suggest that devazepide may have therapeutic utility as an adjuvant to morphine analgesia allowing lower dose of the opiate to be used to relieve pain and reducing the risk of opiate-induced respiratory depression.
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PMID:The cholecystokinin receptor antagonist devazepide enhances morphine-induced analgesia but not morphine-induced respiratory depression in the squirrel monkey. 226 99

Release of cholecystokinin-like immunoreactivity (CCK-LI) in the medial thalamus of conscious rats was measured by brain dialysis and enzyme immunoassay. Analgesia caused by low-frequency electric stimulation of the tibial muscle, the tsusanli acupuncture point, was judged by change of pain threshold due to the stimulation. Medical thalamic CCK-LI released was increased by peripheral electric stimulations of both the acupuncture point and the non-acupuncture point. Results suggest that CCK acts as a neurotransmitter in the medial thalamus, a part of the analgesia inhibitory system.
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PMID:Effect of low-frequency electric stimulation on in vivo release of cholecystokinin-like immunoreactivity in medial thalamus of conscious rat. 227 71

The effects of acute and chronic (22 days) treatment with the cholecystokinin (CCK) antagonists proglumide and lorglumide on antinociception induced by intrathecal (i.t.) morphine were determined at weekly intervals with the rat tail-flick assay. On day 1, acute pretreatment with either proglumide (20 ng, i.t.) or lorglumide (7 ng, i.t.) enhanced morphine (1 microgram, i.t.) analgesia compared to saline (1 microliter, i.t.) pretreatment, but this facilitation was absent on days 8 and 15 of CCK antagonist treatment and was replaced by attenuation of opioid antinociception on day 22. Following termination of daily proglumide or lorglumide injections, normal (control) morphine response was observed after pretreatment with either CCK antagonist on days 29 and 36. Weekly co-administration of either drug with morphine had similar effects: opioid antinociception was initially enhanced on day 1, but this amplification was lost by day 8 and remained absent for the duration of the study (i.e., up to day 36). Inhibition of morphine analgesia, however, was not observed with this treatment paradigm. Chronic daily administration of either CCK antagonist alone did not lower nociceptive thresholds; further, normal opioid response was retained throughout the study in saline treated controls receiving morphine weekly. This study demonstrates that whereas acute i.t. administration of CCK antagonists enhances i.t. morphine antinociception, chronic treatment causes loss of facilitation or attenuation of opioid antinociception, suggesting that (1) compensatory alterations in CCK-opioid interactions develop during chronic CCK blockade and (2) CCK antagonists may not be useful adjuncts to opioid analgesics in the management of chronic pain in man.
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PMID:Chronic administration of cholecystokinin antagonists reverses the enhancement of spinal morphine analgesia induced by acute pretreatment. 236 92

The effects of tifluadom, a benzodiazepine-kappa-opioid-receptor agonist, on cholecystokinin-octapeptide (CCK-8)-induced antinociception were investigated in the mouse writhing test. When given alone, tifluadom produced pronounced, dose-dependent analgesia. The antinociceptive effect of intracerebroventricularly injected CCK-8 was potentiated by high doses of tifluadom. In contrast, when tifluadom was applied at low doses which did not induce antinociception, the antinociceptive effect of CCK-8 was completely antagonized. It is concluded that tifluadom acts both as kappa-opioid receptor agonist and as an antagonist at CCK receptors mediating CCK-induced antinociception.
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PMID:The influence of tifluadom on cholecystokinin-induced antinociception. 236 2

The change in the nociceptive reactions of rats was characterized after stressful acoustic (115 dB) stimulation. Acoustic loading for five minutes resulted in considerable analgesia in the hot-plate test, whereas a significant analgesic response was not observed in the tail-flick test. The analgesic reaction after acoustic stimulation was resistant to naloxone pretreatment and was also found in morphine-tolerant rats, but the acute thermoregulatory and analgesic effects of morphine were greatly potentiated by simultaneous acoustic loading. Substance P or cholecystokinin treatment likewise failed to prevent the analgesic effect of auditory stimulation. No tolerance developed to the analgesic effect on repeated stressing. Diltiazem, a slow calcium channel blocker, facilitated the analgesia. The data suggest a stress-induced analgesia with obviously non-opiate properties, although an indirect involvement of opiate effects could not be excluded.
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PMID:Non-opiate analgesia following stressful acoustic stimulation. 241 94


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