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)

Because several effects of cholecystokinin (CCK) are opposite to those reported for opioids, it seemed likely that CCK may function as an endogenous antagonist of opiate action. This hypothesis was tested initially by assessing the effect of CCK on opiate analgesias. Systemic administration of CCK attenuated opiate analgesias produced by morphine and footshock, but did not reduce nonopiate footshock analgesia. When delivered directly to the lumbosacral spinal cord, a critical site of opiate action, 3.6 ng of CCK-8 significantly inhibited opiate-mediated footshock analgesia; however, 3.6 ng of desulfated CCK-8 did not have an effect. Sequestering of endogenously circulating CCK by antibodies raised against CCK through an active immunization procedure resulted in a potentiation of morphine analgesia. If CCK functions to inhibit opiate involvement in behaviors other than pain responsitivity, CCK-induced satiety may result from an inhibition of opiate-stimulated feeding. In immunohistochemical studies, we have found a dense CCK fiber plexus in the dorsal PVN, a critical site for opiate-induced feeding. Direct microinjections of CCK to this region reduced short-term food intake by 28%. The findings presented here support the hypothesis that an opiate antagonistic function of CCK may account for several previously reported effects of this peptide.
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PMID:Opiate antagonistic function of cholecystokinin in analgesia and energy balance systems. 386 Nov 27

The decapeptide from the frog Hyla caerulea, caerulein (caerulein diethylammonium hydrate, ceruletide, CER) is chemically closely related to the C-terminal octapeptide of cholecystokinin (CCK-8). Like CCK-8, CER and some of its analogues produce many behavioural effects in mammals: inhibition of intake of food and water; antinociception; sedation; catalepsy; ptosis, antistereotypic, anticonvulsive and tremorolytic effects; inhibition of self-stimulation. Effects of CER in man comprise sedation, satiety, changes in mood, analgesia and antipsychotic effects. A modulation of central dopaminergic functions appears to be one possible mechanism of CER and its analogues. A common denominator for all effects of CER is, at present, not evident.
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PMID:Caerulein and its analogues: neuropharmacological properties. 391 10

Cholecystokinin octapeptide (CCK-8), given intracerebroventricularly (icv) or intrathecally (ith) at the dose range of 0.25-4.0 ng, dose-dependently antagonised the effect of morphine analgesia and electroacupuncture analgesia (EAA) in the rat. That CCK-8 antiserum was capable of reversing the tolerance to EAA and changing the non-responders of EAA into responders suggest CCK-8 to be the endogenous anti-opioid substrate and that blocking the effect of CCK-8 may prove to be a powerful way of augmenting the effect of morphine analgesia and EA analgesia.
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PMID:Is cholecystokinin octapeptide (CCK-8) a candidate for endogenous anti-opioid substrates? 400 Apr 12

Proglumide, a cholecystokinin antagonist, potentiates analgesia produced in rats by morphine and endogenous opiates, and appears to reverse tolerance in rats to opiate analgesia. Therefore, proglumide and other cholecystokinin antagonists may be clinically valuable. We have tested proglumide's possible opiate analgesic potentiating effects by examining, in volunteers, the effects of morphine and proglumide on human pain visual analogue scale responses to 45-51 degrees C skin temperature stimuli. Proglumide (50-100 micrograms intravenously) potentiated both the magnitude and duration of analgesia produced by small doses of morphine. This study provides indirect evidence for a cholecystokinin-opiate interaction in humans. Therefore, cholecystokinin antagonists such as proglumide may serve to potentiate exogenous or endogenous opiate action.
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PMID:Potentiation of systemic morphine analgesia in humans by proglumide, a cholecystokinin antagonist. 401 44

Intraperitoneal administration of cholecystokinin (CCK) potently attenuated opiate analgesia produced by footshock. CCK also inhibited opiate footshock analgesia when delivered intrathecally to the lumbosacral spinal cord, a critical site of opiate action in mediating this form of analgesia. However, opiate-independent footshock analgesia was not attenuated by CCK. Morphine analgesia was attenuated by CCK and potentiated by sequestration of peripheral CCK through an active immunization procedure. CCK also was found to suppress food intake in rats when microinjected into the hypothalamic paraventricular nucleus, a site known to mediate opiate-induced feeding. Collectively, the findings reviewed here suggest that an opiate antagonistic action may underlie several of the effects of CCK.
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PMID:Role of cholecystokinin in the control of nociception and food intake. 408 Jul 9

The effect of cholecystokinin octapeptide (CCK-8) and its analogue, ceruletide on release of acetylcholine (ACh) from the cerebral cortex was investigated in urethane-anaesthetized and in unanaesthetized rats. Cholecystokinin octapeptide and ceruletide markedly stimulated output of ACh at doses of 1.5 and 5.0 micrograms/kg (i.p.), respectively. This effect was prevented by proglumide (160 mg/kg i.p.), a specific cholecystokinin receptor antagonist. At doses of 10 micrograms/kg (i.p.) and more, both CCK-8 and ceruletide decreased output of ACh from the cerebral cortex. The decrease was prevented by naloxone (1 mg/kg, s.c.), and replaced by a short-lasting increase. Cholecystokinin octapeptide and ceruletide appear therefore to affect the activity of cortical cholinergic fibres by acting upon both specific and opiate receptors. The interaction between CCK-8 and ceruletide, and opiate receptors either direct or through the release of endogenous opiates, was also demonstrated by the antagonism between ceruletide (1, 5 and 10 micrograms/kg, i.p.) and analgesia induced by morphine (5 mg/kg, s.c.), evaluated by the tail-flick test in the rat.
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PMID:Effect of cholecystokinin octapeptide and ceruletide on release of acetylcholine from cerebral cortex of the rat in vivo. 609 46

The intrathecal administration of capsaicin, a homovanillylamide derivative, has been demonstrated to cause analgesia in response to thermal stimuli. This analgesia has been correlated with a profound depletion of spinal substance P, a putative primary afferent transmitter. We studied the effects of capsaicin, a series of capsaicin analogues, piperine and kainic acid on the immunohistochemical staining of substance P, cholecystokinin, somatostatin, methionine-enkephalin and serotonin. Capsaicin and an analogue 1-nonenoyl-vanillylamide significantly elevated the tail flick latency and when the spinal cords of the rats were analyzed immunohistochemically, a profound depletion of substance P and cholecystokinin was observed. The spinal somatostatin-immunoreactivity of these rats was slightly reduced. Piperine also depleted substance P and reduced somatostatin staining but did not alter the staining intensity or density of cholecystokinin, methionine-enkephalin or serotonin. Kainate-depleted methionine-enkephalin but did not alter any other neuropeptides studied or serotonin. These results may indicate a link between capsaicin-induced analgesia and the concomitant depletion of cholecystokinin and substance P.
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PMID:Effect of intrathecal capsaicin analogues on the immunofluorescence of peptides and serotonin in the dorsal horn in rats. 618 75

The effect of intrathecal injections of morphine and the two peptides, caerulein and cholecystokinin octapeptide (CCK-8), on the activity in ascending axons of the spinal cord evoked by electrical stimulation of primary nociceptive afferents was studied in spinal rats with decerebration. Morphine (20 microgram) depressed the spontaneous activity and the activity evoked from either A delta-or C-fibres. The co-activation by A delta-fibre stimulation of ascending axons activated by stimulation of C-fibres and the activity in ascending axons activated by stimulation of afferent A beta-fibres were not influenced by morphine. C-Fibre-evoked ascending activity was also depressed by morphine (10 microgram and 5 microgram). Ascending nociceptive activity was not changed by caerulein (30 ng) and CCK-8 300 ng, but it was depressed by a subsequent injection of morphine (20 microgram). The depressant effects of morphine were abolished by an intravenous injection of concluded that: (i) an intrathecal injection of morphine selectively depressed the ascending nociceptive activity; (ii) the depression produced by morphine is an equivalent for spinal analgesia following intrathecal injection of morphine to man; and (iii) the two components of the spinal nociceptive system, the motor and the sensory path, can independently be influenced by drugs.
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PMID:Analgesic effect of intrathecal morphine demonstrated in ascending nociceptive activity in the rat spinal cord an in effectiveness of caerulein and cholecystokinin octapeptide. 627 33

The analgesic action of beta-endorphin, as observed in the hot plate test with rats, was effectively suppressed by intracerebroventricular (i.c.v.) injection of caerulein and cholecystokinin octapeptide (CCK-8). The effect of caerulein was particularly striking; this peptide in doses of more than 0.09 nM lessened or abolished the analgesic effect of beta-endorphin in a dose of 0.7 nM. On the other hand, non sulfated CCK-8 had no significant effect on beta-endorphin-induced analgesia.
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PMID:Caerulein and cholecystokinin suppress beta-endorphin-induced analgesia in the rat. 628 27

The endogenous neuropeptide cholecystokinin, when administered systemically or perispinally, potently antagonizes opiate analgesia produced by foot shock and morphine. Nonopiate foot-shock analgesia is not reduced by this neuropeptide. The spinal cord appears to be a critical site of cholecystokinin action. These experiments suggest a physiological role for cholecystokinin as a specific opiate antagonist in analgesia-mediating systems. A similar mode of action may explain other behavioral effects of cholecystokinin, such as suppression of food intake.
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PMID:Evidence for the neuropeptide cholecystokinin as an antagonist of opiate analgesia. 629 31


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