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)

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 the selective CCK-A antagonist L-365,031 and the selective CCK-B antagonist L-365,260 on morphine analgesia and opiate tolerance and dependence in rats were examined. L-365,031 and L-365,260 had no effect on baseline pain thresholds in the radiant heat tail flick test but enhanced analgesia induced by a submaximal dose of morphine (4 mg/kg). Similarly, L-365,260 did not effect pain thresholds in the paw pressure test but enhanced morphine analgesia in this model. Rats injected twice daily for 6 days with incremental doses of morphine became tolerant to the analgesic effects of the drug. Twice daily injections of either 8 mg/kg L-365,031 or 0.2 mg/kg L-365,260 prevented the development of tolerance to morphine analgesia. In contrast, L-365,260 had no influence on the development of opiate dependence in these animals, as assessed by naloxone-precipitated withdrawal. The results of the present study, when considered together with previous data, indicate that the rank order of potency of non-peptide CCK antagonists for enhancing morphine analgesia is L-365,260 greater than MK-329 greater than L-365,031. This rank order correlates well with the potency of the antagonists in blocking CCK-B receptors in rodents and suggests that CCK/opiate interactions in this species are mediated by CCK-B receptors.
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PMID:The selective CCK-B receptor antagonist L-365,260 enhances morphine analgesia and prevents morphine tolerance in the rat. 231 58

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

This article has centered on the hormonal actions of CCK on a variety of different target tissues. Until the development of specific assays for measuring plasma levels of the hormone, it was not possible to distinguish physiologic from pharmacologic effects. However, by the methods described earlier it now has become clear that CCK, in physiologic concentrations, stimulates gallbladder contraction, delays gastric emptying, potentiates insulin secretion, and may affect satiety. Actions of CCK that have been studied by radioimmunoassay methods and determined also to be physiologic include stimulation of pancreatic exocrine secretion. Other actions of CCK that may be physiologic but have not been thoroughly investigated include effects on bowel motility, relaxation of lower esophageal sphincter pressure, regulation of sphincter of Oddi pressure, effects on analgesia, and modification of behavior. Some of these actions may be attributable to endogenous, but neurally released CCK and, therefore, would not be hormonal actions. However, continued investigations with specific CCK receptor antagonists together with accurate measurements of circulating levels of CCK should make it possible to define the physiologic importance of CCK on these other potential sites of action. The variety of CCK's physiologic effects emphasizes its integrative function on both digestive and metabolic processes. After a meal, in a highly coordinated fashion, CCK (1) regulates the movement of nutrients through the gastrointestinal tract, (2) contracts the gallbladder and stimulates pancreatic exocrine secretion to facilitate digestion, and (3) potentiates amino acid-induced insulin secretion and delays gastric emptying to maintain euglycemia. An effect to reduce food intake following food ingestion would be a logical extension of these integrated actions. Thus, CCK appears to have an essential role in regulating the intake, processing, and distribution of essential nutrients.
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PMID:Integrated actions of cholecystokinin on the gastrointestinal tract: use of the cholecystokinin bioassay. 248 53

Sulfated cholecystokinin octapeptide (CCK-8; Asp-Tyr-SO3H-Met-Gly-Trp-Met-Asp-Phe-NH2) produced analgesia in mice when administered i.c.v. and tested in the acetic acid-induced writhing assay. The ED50 was found to be 0.03 nmol/mouse which was about 3, 24 and 714 times more potent than morphine. [D-Pen2,D-Pen5]enkephalin and U50,488H [trans-(+/-)-3,4-dichloro-N-methyl-N-[2-(1-pyrolidinyl)cyclohexyl] benzeneacetamidel], respectively. When administered i.t., CCK-8 produced partial analgesia of up to 22 to 23% at low doses ranging from 15 to 60 ng/mouse and hyperalgesia at doses over 120 ng/mouse. Naloxone, an opioid antagonist, inhibited the analgesia induced by CCK-8 (i.c.v. and i.t.) but potentiated hyperalgesia induced by CCK-8 (i.t.). Apparent pA2 value for CCK-8 (i.c.v.) against naloxone (s.c.) was 5.88 which was significantly different from those for morphine-naloxone and U50,488H-naloxone but was not significantly different from that for [D-Pen2,D-Pen5]enkephalin-naloxone. Studies using highly selective opioid antagonists showed that CCK-8-induced analgesia was significantly antagonized by the delta receptor antagonist, ICI154,129 [(Allyl)2-Tyr-gly-gly-psi-(CH2S)-Phe-Leu] but not by beta-funaltrexamine, a highly selective mu receptor antagonist or nor-binaltorphimine, a highly selective kappa receptor antagonist. Opioid receptor binding study using [3H]-[D-Ala2,D-Leu5]enkephalin (+unlabeled [D-Ala2,MePhe4,Gly-ol5]enkephalin) in mouse brain membrane preparations revealed that there were no changes in the maximum binding or Kd of delta opioid binding sites in the presence of CCK-8 (1 microM) in vitro.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Indirect involvement of delta opioid receptors in cholecystokinin octapeptide-induced analgesia in mice. 255 28

We have reported that intracerebroventricular (i. c. v.) injection of 1-4 ng of CCK-8 to the rat produced a remarkable antagonistic effect on morphine analgesia. In order to study the species specificity and the site of action, CCK-8 was microinjected into the PAG of the rabbit, and its influence on morphine analgesia and electroacupuncture analgesia was observed. The latency of the escape response (ERL) to radiant heat focused on the snout was measured as an index of the pain threshold. Microinjections were made via cannulae chronically implanted into the PAG. The drug solutions were delivered in a volume of 1 microliter, at a speed of 0.125 microliter/min. The ERL was measured for a period of 60 or 70 minutes at 10 min intervals. 1. CCK-8 administered unilaterally to the PAG of the rabbit at a dose of 3 ng antagonized the analgesia induced by morphine (4 mg/kg, i. v.) by 73% (P less than 0.001), and reduced the analgesic effect of electroacupuncture by 67% (P less than 0.001). These effects were dose-dependent within the range from 1.5 ng to 6.0 ng. The effect of CCK-8 was reversed by CCK receptor blocker proglumide (4 microliters, intra-PAG injection). Unsulfated CCK-8 (CCK-us) had no effect in this regard. These results indicate that in the PAG of the rabbit, exogenously administered CCK-8 was capable of antagonizing opioid analgesia by the activation of CCK receptors. 2. Two groups of rabbits were given with morphine (2 mg/kg, i. v.) and simultaneous injection of CCK-8 antiserum (CCK-AS, 1 microliter) or normal rabbit serum (NRS) into the PAG.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Antagonism of morphine analgesia and electroacupuncture analgesia by cholecystokinin octapeptide (CCK-8) administered in periaqueductal gray (PAG) of the rabbits]. 260 48

The octapeptide form of CCK predominates in the central nervous system (CNS) of mammalian species, including man. Many of the physiological roles of CCK in the CNS are unknown, but it is believed to be involved in nociception. CCK is distributed throughout cortical grey matter, periaqueductal grey matter, ventromedial thalamus and spinal dorsal horn, all of which are areas known to be associated with pain modulation. CCK receptor subtypes have been identified and may be classified according to their affinity for the sulphated and desulphated forms of CCK-8 and the recently described selective antagonist. MK-329. CCK-A receptors have high affinity for sulphated CCK-8 and for MK-329 but low affinity for desulphated CCK-8 and CCK-4 whilst CCK-B sites bind MK-329 with low affinity and discriminate poorly between sulphated and desulphated CCK-8. CCK-A receptors are found predominantly in peripheral tissues but they also exist in discrete regions of the primate CNS, including the spinal cord. CCK-B receptors are found ubiquitously throughout other regions of the neuraxis. The results of studies on the effects of CCK-8 and the decapeptide analogue caerulein on pain thresholds are conflicting. Some workers suggest that large doses of CCK-8 and caerulein induce naloxone-reversible analgesia in certain pain models. However, it appears likely that analgesia induced by large doses of CCK and caerulein in animals may be a pharmacological rather than a physiological phenomenon. Accordingly, others have found that small (and most probably, physiological) doses of CCK-8 attenuate the analgesic effects of morphine, and of endogenous opioids. Thus, it has been proposed that CCK may act as an endogenous opiate antagonist. Studies in rats with the selective CCK antagonist MK-329 have helped clarify the interaction between CCK and morphine-induced analgesia. Treatment with MK-329 enhances morphine analgesia and chronic treatment with MK-329 prevents the development of tolerance to morphine analgesia. However, the antagonist does not prevent naloxone-precipitated withdrawal symptoms in morphine-dependent rats. In man, caerulein prevents pain associated with gall-bladder contraction, probably by relaxation of the sphincter of Oddi. Caerulein has also been shown to reduce renal colic and the pain of intermittent claudication. Preliminary clinical studies with the weak, non-selective, CCK antagonist proglumide, indicate an enhancement of morphine analgesia. As yet, no studies have demonstrated analgesic effects of CCK antagonists in man when administered alone.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:The role of CCK caerulein, and CCK antagonists in nociception. 269 75

The analgesic effect of systemic morphine (5 mg/kg, s.c.) was dose-dependently antagonized by CCK-8 administered to the periaqueductal gray (PAG) of the rat. This effect could be reversed by proglumide, a CCK-receptor antagonist. The effect of morphine analgesia was potentiated by proglumide administered to PAG. These results are compatible with the notion that PAG is a strategic site where CCK-8 exerts an antiopioid activity.
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PMID:Cholecystokinin-octapeptide antagonizes morphine analgesia in periaqueductal gray of the rat. 271 44

The effects of the potent and selective CCK antagonist, MK-329, on morphine- and environmentally-induced analgesia were examined in male mice. The results show that MK-329 (0.005-0.1 mg/kg) was devoid of intrinsic analgetic activity on the mouse tail-flick assay and, over the dose range 0.01-0.5 mg/kg, was without significant effect upon non-opioid analgesia, induced by defeat experience. However, opposite effects of MK-329 on analgesia induced by morphine and opioid-mediated social conflict analgesia were observed. That is, 0.05-0.01 mg/kg MK-329 (but not smaller doses) enhanced, and modestly prolonged, the duration of analgesia induced by 5 mg/kg morphine. In direct contrast, 0.0001-0.5 mg/kg of the CCK antagonist very potently inhibited opioid-typical analgesia in mice exposed to intense conspecific attack. In the latter studies, a residual short-lasting analgesia in mice, treated with MK-329, was found to be resistant to naloxone (5 mg/kg), indicating its non-opioid nature and confirming the lack of effect of the CCK antagonist on opioid-independent analgesia. It is suggested that the variable effects of MK-329 on morphine-induced and opioid-mediated social conflict analgesia may reflect differential, dose-dependent effects at CCK-B and CCK-A sites respectively, a proposal consistent with the 500-fold potency difference observed between the two models.
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PMID:Differential effects of the CCK antagonist, MK-329, on analgesia induced by morphine, social conflict (opioid) and defeat experience (non-opioid) in male mice. 281 81

The conditions under which CCK-8-S may block opiate-induced analgesia were examined in detail. A U-shaped dose-response relationship was observed for the ability of CCK-8-S to attenuate (by approximately 50%, at most) morphine-induced tail flick analgesia. The analgesic effects of morphine in the hot plate or acetic acid-induced stretching tests were not altered by CCK-8-S at doses that antagonized morphine in the tail flick test. Tail flick latency elevations induced by meptazinol, a putative mu-1 receptor agonist, were also attenuated by CCK-8-S according to a U-shaped dose-response relationship, but those induced by U-50,488, a kappa agonist, were not antagonized by CCK-8-S doses that attenuated morphine analgesia. Thus, the ability of CCK-8-S to antagonize opiate analgesia does not follow a conventional dose-response relationship, does not extend to all tests of analgesia and may not extend to all opioid drugs. Analgesia mediated by the mu-1 opioid receptor subtype may be more amenable to antagonism by CCK-8-S than that mediated by the kappa receptor subtype.
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PMID:Antagonism of morphine analgesia by CCK-8-S does not extend to all assays nor all opiate analgesics. 324 51


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