Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0344307 (analgesia)
 28,200 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The potent and selective non-peptide cholecystokinin (CCK) antagonist L-364,718 (0.5-2.0 mg/kg s.c.) enhanced the analgesia induced by acute morphine treatment in the rat tail flick test. Chronic treatment with L-364,718 (1.0 mg/kg) prevented the development of tolerance to morphine analgesia (after a 6 day period of morphine treatment) but did not influence the onset of opioid dependence. Since L-364,718 is considerably more potent in inhibiting CCK binding to peripheral tissues than to brain membranes its interaction with morphine is surprising. The exact locus of this interaction, or whether it involves 'peripheral-type' (CCK-A) or 'central-type' (CCK-B) receptors is not known.
 ...
PMID:Enhancement of morphine analgesia and prevention of morphine tolerance in the rat by the cholecystokinin antagonist L-364,718. 337 66

Tolerance to morphine analgesia was induced in rats by chronic treatment with morphine (5-30 mg/kg, t.i.d. for 6 days). Intracerebroventricular (i.c.v.) injection of antiserum against cholecystokinin octapeptide (CCK-8) reversed tolerance to morphine by 50% (P less than 0.001). Intrathecal (ith) injection of the CCK-8 antiserum produced a similar, although less marked, reversal of tolerance to morphine. Rats made tolerant to analgesia induced by morphine developed a cross tolerance to electroacupuncture-induced analgesia. This cross tolerance was also reversed by the CCK-8 antiserum by more than 50% (P less than 0.001). Intracerebroventricular or intrathecal injection of the CCK-8 antiserum per se produced no significant changes in the basal level of the latency of the tail flick response, nor did it affect the analgesia induced by morphine in naive rats. The results suggest that prolonged activation of opioid receptors may trigger the CCK-8 system in the central nervous system to exert a negative feedback control, which may constitute one of the mechanisms for the development of tolerance to opioids.
 ...
PMID:Reversal of tolerance to morphine but no potentiation of morphine-induced analgesia by antiserum against cholecystokinin octapeptide. 349 37

The analgesic effect produced by electroacupuncture (EA) stimulation in the rat was dose-dependently antagonized by cholecystokinin octapeptide (CCK-8) administered intracerebroventricularly (i.c.v.) or intrathecally (i.th) at a dose range of 0.25-4 ng. This effect had an immediate onset and lasted for at least 4 h. CCK-8 per se, however, did not affect baseline tail flick latency. Rats subjected to prolonged EA stimulation developed EA tolerance as well as cross-tolerance to morphine. These tolerances could be postponed or reversed by i.c.v. or i.th injection of antiserum against CCK-8. While CCK-8 antagonized opioid analgesia, it did not affect analgesia induced by 5-hydroxytryptamine (5-HT) or norepinephrine (NE). Moreover, CCK-8 antiserum did not alter the basic level of nociception, nor did it potentiate EA analgesia in naive rats. It is concluded that prolonged EA stimulation results in a profound release of opioids which may trigger the release of CCK-8 in the central nervous system to counteract the opioid component of EA analgesia. This mechanism may account, at least in part, for the development of EA tolerance.
 ...
PMID:Cholecystokinin octapeptide (CCK-8): antagonism to electroacupuncture analgesia and a possible role in electroacupuncture tolerance. 349 55

The observation that the narcotic antagonist naloxone could inhibit analgesia produced by electrical stimulation of the brain indicated the involvement of an endogenous chemical in the relief of pain. Multiple endogenous opioid peptides have been identified that have similar pharmacological properties to known narcotic analgesics. The biosynthesis, release, and degradation of opioid peptides have been studied in order to better understand how the manipulation of endogenous opioid systems can be used to produce or augment analgesia. The results of our studies reveal that various conditions and manipulations, such as electrical brain stimulation, acupuncture, stress, and the administration of opioid analgesics, can cause the release of endogenous opioid peptides and possibly endogenous nonpeptide substances. It has also been discovered that nonopioid peptides, such as cholecystokinin, calcitonin, and angiotensin II, can alter the action of opioid analgesics by antagonizing or potentiating their effects. An understanding of the role of endogenous peptides in endogenous opioid mechanisms is necessary for the development of new ways to treat pain and such other disorders as sleep apnea in children (sudden infant death syndrome), head injury, and opioid addiction that involve the activation or alteration of endogenous opioid systems.
 ...
PMID:The role of endogenous peptides in the action of opioid analgesics. 352 91

A double-label immunofluorescence technique was used to demonstrate that immunoreactivities for the functionally antagonistic neuropeptides enkephalin and cholecystokinin octapeptide (CCK) are co-localized within individual neurons and processes in discrete areas of rat midbrain and forebrain. Coexistence was most prominent within varicose pericellular axons extending from the periaqueductal gray matter to a field overlying the medial lemniscus, axons and terminal-like puncta in the central medial, paracentral, interanterodorsal and ventral anterior thalamic nuclei, and perikarya and proximal axonal fragments in layers II and III of neo- and allocortex, and in the anterior olfactory nucleus. The former two systems of axons lie in areas of spinothalamic tract termination. These data suggest that some of the antagonism of opioid analgesia by CCK occurs at the synaptic level in nociceptive areas of brain-stem and thalamus where CCK and enkephalin are co-localized and presumably co-released.
 ...
PMID:Co-localization of enkephalin and cholecystokinin in discrete areas of rat brain. 354 90

Since cholecystokinin (CCK) has been suggested to be an endogenous opiate antagonist, we tried to evaluate if this peptide could be involved in the development of tolerance to morphine. Naive rats were chronically administered morphine, either alone or concomitantly with proglumide or benzotript, two putative CCK receptor antagonists. Chronic treatments with both CCK antagonists alone were also established. Drugs were administered by the oral route, dissolved in the drinking water. At the end of the chronic treatments, the development of tolerance to morphine was assessed by an evaluation of the analgesic responses evoked by graded doses of acutely injected morphine in the tail-flick and hot plate tests. Proglumide and benzotript were able to inhibit the shift to the right of the dose-response curve for morphine, i.e. they prevented the development of tolerance to morphine-induced analgesia. Chronically given alone, the two CCK antagonists never modified the responses to the acute challenge with morphine. We also determined the development of physical dependence by looking at the withdrawal syndrome precipitated by graded doses of acutely injected naloxone. In these experiments the concomitant treatment with morphine and proglumide or benzotript did not modify the occurrence of dependence. These observations are consistent with the hypothesis of CCK being an endogenous opiate antagonist, involved in the development of tolerance to morphine-induced analgesia but not of dependence. Moreover, tolerance to and dependence on morphine can be pharmacologically dissociated.
 ...
PMID:Dissociation of tolerance and dependence to morphine: a possible role for cholecystokinin. 358 Aug 99

The C-terminal octapeptide of cholecystokinin (CCK 8) was administered intrathecally to rats. Doses in the nanogram range produced weak but significant antinociception in the paw pressure test five minutes after injection whereas microgram doses of CCK 8 produced hyperalgesia. The CCK 8-induced analgesia or hyperalgesia was not seen in the tail flick test and was not associated with motor incapacitation or any other noticeable side effects. The C-terminal tetrapeptide of CCK (CCK 4) and pentagastrin were found to be ineffective in all tests but caerulein and molluscan cardioexcitatory neuropeptide (FMRF-amide), like CCK 8, produced antinociception in the paw pressure test.
 ...
PMID:CCK 8 analgesia and hyperalgesia after intrathecal administration in the rat: comparison with CCK-related peptides. 367 May 69

Cholecystokinin (CCK) has potent antinociceptive properties when given either peripherally or centrally. An interaction between opiate and CCK-induced antinociception is indicated as CCK-induced analgesia is potentiated by naloxone. Since CCK cells in Periaqueductal grey (PAG) are known to be sensitive to both noxious stimuli and i.v. morphine, the possibility that the PAG was the site of such an interaction was investigated by an in vitro study of the effects of morphine and naloxone on CCK release in PAG. The K+-evoked release of CCK from tissue slices of PAG was unaffected by a wide range of concentrations of morphine. However, after pretreatment with naloxone (10(-9) M), morphine (10(-7)-10(-6) M) caused a significant, dose dependent attenuation of CCK release (70% inhibition at 10(-6) M). These results suggest that the release of CCK in PAG is modulated by opioid systems.
 ...
PMID:Morphine action on cholecystokinin octapeptide release from rat periaqueductal grey slices: sensitisation by naloxone. 368 73

Recent evidence has suggested that cholecystokinin (CCK) may act as a physiological opiate antagonist. Both the overlap of CCK and opiate systems within the central nervous system and the fact that exogenous CCK can antagonize opiate analgesia suggest that endogenous CCK systems interact with opiate-mediated pain inhibitory systems. In the present series of experiments, we examined the effect of the CCK receptor antagonist proglumide on various forms of morphine analgesia. We have observed that proglumide can potentiate morphine analgesia following systemic, intrathecal or intracerebral administration of these drugs. Endogenous CCK systems do not appear to be tonically active since neither systemic, intrathecal nor intracerebral proglumide typically produced measurable analgesia in the absence of morphine. These data suggest that CCK may be released in response to opiate administration and acts to return the organism toward its basal level of pain sensitivity. If such a hypothesis is in fact true, then CCK blockade may be of clinical value in the treatment of pain.
 ...
PMID:Potentiation of morphine analgesia by the cholecystokinin antagonist proglumide. 383 90

We have recently observed that exogenous sulfated cholecystokinin octapeptide (CCK) can antagonize various forms of opiate analgesia and that the CCK receptor blocker proglumide potentiates morphine analgesia. These observations, plus the similarity in the distribution of CCK and opiate systems, suggest that endogenous CCK may act as a physiological opiate antagonist. We have extended these initial studies by examining the effect of CCK antagonists on opiate analgesia produced by release of endogenous opiates (front paw footshock induced analgesia) and by intrathecal administration of D-Ala-methionine enkephalinamide, a stable analogue of an endogenous opiate. Additionally, the specificity of proglumide's effect was examined by testing the effect of this drug on various forms of non-opiate analgesia. This series of experiments demonstrate that CCK antagonists can markedly potentiate analgesia induced by endogenous opiates and provide strong support for the hypothesis that endogenous CCK systems can oppose the analgesic effects of opiates. Potentiation of analgesia by CCK receptor blockers appears to be selective for opiate systems since proglumide typically attenuated or had no effect on various forms of non-opiate analgesia. These data suggest that CCK blockers may be clinically useful for enhancing the analgesic effects of procedures such as acupuncture, which may be mediated by release of endogenous opiates.
 ...
PMID:Cholecystokinin antagonists selectively potentiate analgesia induced by endogenous opiates. 383 91


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>