Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0030193 (pain)
 261,466 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Two varieties of neurons were found in nucleus parafascicularis (pf) of the rat: one responds to noxious stimuli with an increase in firing (pain-excited neuron, PEN), the other with a decrease in firing (pain-inhibited neuron, PIN). Electroacupuncture (EA) has been shown to suppress PEN and excite PIN, which can be taken as an electrophysiological index for EA analgesia. This effect of EA subsided after prolonged (6 h) EA stimulation, suggesting the development of tolerance to EA. Intracerebroventricular (icv) injection of CCK-8 antiserum aiming at neutralizing endogenously released CCK-8 resulted in a complete restoration of the EA effect. Normal rabbit serum was not effective. CCK-8 antiserum per se did not affect the firing pattern of the PEN or PIN in nontolerant rat. The results obtained from single neuron recording in anesthetized animals thus confirmed those obtained in intact animals using the tail flick as the end point, implying that an excess of endogenously released CCK-8 may constitute one of the mechanisms for the development of EA tolerance.
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PMID:Reversal of electroacupuncture tolerance by CCK-8 antiserum: an electrophysiological study on pain-related neurons in nucleus parafascicularis of the rat. 822 97

Amongst the spinal peptide candidates believed to be involved in the mediation of analgesia, only somatostatin fulfills the criterium of a real analgesia substance. Spinal somatostatin specifically blocks the transmission of painful stimuli. Spinal calcitonin may lower the opioid dose requirement in patients with bone metastases but it fails to relieve acute pain. The usefulness of ACTH and CRF for treatment of pain remains to be established. The role of CCK-8, vasopressin and neurotensin is unclear. The contradictory findings on antinociception using simple rodent withdrawal reflex tests (e.g. the tail flick test), or more complex behavioral tests in which supraspinal sensory processing is involved, (e.g. the hot plate test), indicate that these tests are inappropriate when neuropeptides are employed. Furthermore, due to their inability to predict analgesia in humans, they do not fulfill the guidelines proposed by the IASP that animal test procedures have to be for the benefit of humans.
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PMID:Non-opioid peptides for analgesia. 831 62

A study was carried out on Met- and Leu-enkephalin, Gastrin/CCK-, SP-, CGRP-, NPY-immunoreactive fibers using paraffin sections of dental pulp taken from 8 apparently normal teeth (wisdom teeth or teeth extracted for orthodontic reasons). Within the limitations of the samples studied, dental pulp is characterized by the presence of sensory (Enkephalin-, Gastrin/CCK-immunoreactive) and pain fibers (SP-immunoreactive) and of fibers with a potent vasodilatory action (CGRP-immunoreactive) and by the absence of fibers with a vasoconstrictor action (NPY-immunoreactive).
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PMID:Pulpal neuropeptidergic fibers. 839 52

This review has covered the five potential causes for opioid poorly responsive pain, namely (a) a loss of opioid receptors on the spinal terminals of C-fibres as a result of peripheral nerve damage, (b) an accumulation of morphine-3-glucuronide, (c) changes in the non-opioid peptides, F8Fa or CCK, either spinally or supraspinally, (d) actions of the opioid peptide dynorphin and (e) spinally generated hypersensitive states via activation of the NMDA receptor. The loss of opioid receptors is likely to be important where peripheral nerve pathology or compression occurs, but the evidence suggests that increasing the dose will overcome the reduced opioid response. Morphine-3-glucuronide is unlikely to be a factor, nor is dynorphin, but the endogenous peptides CCK and F8Fa may be important. Finally, there is an association between the NMDA receptor and hyperalgesia/allodynia and reduced opioid sensitivity. Dextrorphan and ketamine reduce NMDA mediated events and so are available to test this hypothesis.
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PMID:Neurophysiology of opioid poorly responsive pain. 856 99

Pharmacological intervention with either cholecystokinin-8 (CCK-8) or morphine during 99mTc- hepatoiminodiacetic acid (HIDA) cholescintigraphy is required primarily for the assessment of the diseases affecting the gallbladder, the common bile duct, or the sphincter of Oddi. For imaging, the patient should be prepared by an overnight fast, or with 4 hours of minimum fast. Pre-emptying with CCK-8 is probably undesirable and should either be avoided or one should wait for at least 4 hours after CCK-8 to begin the 99mTc-HIDA study to achieve higher specificity of the test for acute cholecystitis. When he gallbladder is not observed by 60 mins in a clinical setting of acute cholecystitis, a dose of 0.04 mg/kg of morphine is administered intravenously and imaging continued for an additional 30 mins. Nonvisualization of the gallbladder by 90 mins with morphine in an appropriate clinical setting is diagnostic for acute cholecystitis. When the gallbladder is not observed by 60 min but is seen with morphine administered after 60 mins, a positive diagnosis of abnormal gallbladder function can be made. When the gallbladder is observed in a clinical setting of biliary pain or chronic calculous or acalculous cholecystitis, CCK-8 at a dose rate of 3.3 ng/kg/min is infused intravenously for 3 mins (10 ng/kg/3 min) for the measurement of the ejection fraction. An ejection fraction value of less than 35% is indicative of calculous or acalculous chronic cholecystitis. The gallbladder emptying is directly related to the total number of cholecystokinin receptors in the smooth muscle. The ejection fraction can be controlled to any desired level simply by controlling the dose rate or the duration of infusion of CCK-8. Morphine and other opiate metabolites circulate for many hours in blood and act on the sphincter of Oddi and decrease the gallbladder ejection fraction. Careful drug history, especially that of opiates, is very critical in all subjects with a low ejection fraction before assigning an abnormality to the gallbladder motor function.
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PMID:Cholecystokinin and morphine pharmacological intervention during 99mTc-HIDA cholescintigraphy: a rational approach. 862 48

We studied the effect of cholecystokinin (CCK-8) and yohimbine-alpha-2-adrenoreceptor antagonist administered locally into lateral reticular formation (LRF) on the bioelectrical response to the pain stimulation. The experiments were carried out on 8 conscious rabbits with bilaterally implanted electrodes into: motor-sensory cortex, ventro-postero-lateral thalamic nuclei, hippocampus and LRF. Nociceptive stimulation was performed by means of electrical pulses applied to the front paw. Bioelectrical activity (BA) of the chosen brain structures was analysed by means of spectral analysis (FFT) and directed transfer function (DTF). The results of our study may suggest that supraspinal administration of CCK-8 together with yohimbine have inhibitory effect on nociceptive transmission.
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PMID:Influence of CCK-8 and yohimbine on supraspinal modulation of nociceptive process. 878 81

The ability of the selective cholecystokinin(B) (CCK(B)) receptor antagonist L-365,260 (0.2 mg/kg s.c.) to modulate the antinociceptive action of relatively low doses of systemic morphine (0.1, 0.3 and 1.0 mg/kg i.v.) was evaluated using a well established rat model of peripheral unilateral mononeuropathy. Behavioural tests based on both mechanical (vocalization threshold to paw pressure) and thermal (struggle latency after immersion of the paw into a cold (10 degrees C), warm (44 degrees C) or hot (46 degrees C) water bath) stimuli were used. Experiments were performed 2 weeks after the surgery when the pain-related behaviour has fully developed. We demonstrated a differential effect of L-365,260 depending both on the dose of morphine and the test used. Pretreatment with the CCK(B) receptor antagonist (0.2 mg/kg) inverted the ineffectiveness of the lowest dose (0.1 mg/kg i.v.) of morphine against the noxious (46 degrees C) thermal stimulus, and the effect of the combination was equal to that seen after the dose 0.3 mg/kg of morphine alone. Likewise, in the mechanical test, the already enhanced effect of this dose (0.1 mg/kg) of morphine on the nerve-injured paw was further increased (by 4-fold) after L-365,260 pretreatment. These effects were abolished by naloxone (0.01 mg/kg i.v.). However, the effects of the higher doses (0.3 and 1.0 mg/kg i.v.) of morphine against the mechanical or noxious thermal stimuli were not significantly enhanced by pretreatment with the CCK(B) receptor antagonist. Further, L-365,260 was found to be completely ineffective in modulating the responses to morphine at 10 degrees C and at 44 degrees C.
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PMID:In mononeuropathic rats, the enhancement of morphine antinociception by L-365,260, a selective CCK(B) receptor antagonist, depends on the dose of systemic morphine and stimulus characteristics. 916 62

The analgesic effects of the rat in response to electroacupuncture (EA) or low-dose morphine (3 mg/kg) show marked individual variations. In the midbrain periaqueductal gray (PAG) of the rat, the content of the neuropeptide cholecystokinin octapeptide (CCK-8) was found to be significantly higher in the low responder (LR) rats as compared to that in the high responders (HR). Since PAG has been shown to be a strategic site for CCK-8 to exert an anti-opioid action, a high CCK content in PAG may account for the low analgesic responsiveness to EA and morphine. In order to block the expression of the gene encoding preproCCK in the brain, antisense CCK expression vector pSV2-CCKAS was microinjected into the lateral cerebral ventricle of the rat, leading to a decrease of the CCK-mRNA as well as the CCK-8 content in rat brain. This effect started 4 days after the intracerebroventricular (i.c.v.) injection of the antisense expression vector, and lasted no more than 1 week. This procedure was shown to be very effective in converting LR rats into HR for EA analgesia and morphine analgesia, and also delayed the development of tolerance elicited by prolonged EA stimulation or repeated morphine administration. The time course of the augmentation of opioid analgesia (4-6 days after the i.c.v. injection of the expression vector) paralleled the decrease of the brain CCK-8 content. The results argue that blocking the CCK gene expression in the brain may tilt the balance between opioid and anti-opioid peptides in favor of the former, thus strengthening the EA analgesia and morphine analgesia, and delaying the development of opioid tolerance.
Pain 1997 May
PMID:Cholecystokinin antisense RNA increases the analgesic effect induced by electroacupuncture or low dose morphine: conversion of low responder rats into high responders. 920 Jan 76

The ability of pretreatment by the selective cholecystokinin-B (CCK(B)) receptor antagonist L-365,260 (0.2 mg/kg s.c.) to prevent the development of tolerance to the antinociceptive action of morphine was evaluated by a well-established rat model of unilateral peripheral mononeuropathy. The 4-day pretreatment regimens (saline, L-365,260 or morphine alone, or with the combination of L-365,260 and morphine) were begun on postoperative day 12. The experiments were performed on day 16, when the pain-related behavior reached a stable maximum. Behavioral test based on a mechanical stimulus (vocalization threshold to paw pressure) and relatively low acute doses of systemic morphine (0.1, 0.3 and 1.0 mg/kg i.v.) were used. On day 16, the base-line vocalization threshold to paw pressure values of the groups pretreated with one of the four regimens were similar, which suggests that the pretreatments had no effect on the development of mechanical allodynia. Pretreatment with morphine alone (10 mg/kg s.c., two times a day during 4 days) induced a complete tolerance to the antinociceptive effect of acute morphine (0.1-1.0 mg/kg i.v.). However, pretreatment with the combination of L-365,260 with morphine completely prevented the development of tolerance to the antinociceptive effect of acute i.v. morphine. The effect of acute morphine in this latter pretreatment group was dose dependent, naloxone reversible and similar to the effect of acute morphine seen in the saline-pretreated group. Our results suggest that in this well-characterized model of neuropathic pain, the development of tolerance to the antinociceptive effect of systemic morphine can be prevented by systemic coadministration of the CCK(B) antagonist L-365,260. We further show, that in contrast to a tonic activity of the endogenous opioidergic system, a tonic activity of the endogenous CCK system cannot be revealed in this rat model of neuropathic pain.
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PMID:Prevention of tolerance to the antinociceptive effects of systemic morphine by a selective cholecystokinin-B receptor antagonist in a rat model of peripheral neuropathy. 931 48

Patients with typical symptoms of biliary tract disease but no gallstones on ultrasonography may benefit from cholecystectomy for presumed chronic acalculous cholecystitis. We retrospectively analyzed the outcome of 50 patients with a preoperative diagnosis of chronic acalculous cholecystitis based upon history (chronic or recurrent, postprandial right upper quadrant abdominal pain), the absence of acid-peptic disease, and normal biliary sonography treated with laparoscopic cholecystectomy (LC) and transcholecystic cholangiography from 1991 to 1996. All patients had preoperative cholecystokinin-stimulated hepatobiliary scintigraphy (CCK-HBS). There were 42 women and 8 men with a mean age of 43 years. CCK-HBS was abnormal in 45 patients (< or = 35 per cent gallbladder ejection fraction or nonfilling of the gallbladder). There was no postoperative mortality and one morbidity (urinary retention). All patients had microscopic evidence of chronic cholecystitis. At mean follow-up of 30 months, (range, 7-62 months) 39 patients (78%) were free of abdominal pain. Thirty-five of 45 patients with abnormal CCK-HBS were pain free (positive predictive value, 0.78). Four of five patients with normal CCK-HBS were pain free (negative predictive value, 0.20). The positive and negative likelihood ratios for CCK-HBS were 0.99 and 1.13, respectively, confirming that this test was not useful for predicting benefit from LC. Seven patients with persistent right upper quadrant pain had abnormal postoperative sphincter of Oddi manometry; they improved after endoscopic sphincterotomy. Patients with symptoms typical of biliary colic with normal gallbladder sonography and absence of acid-peptic disease benefit from LC in the majority of cases. Those who remain symptomatic after LC may benefit from endoscopic retrograde cholangiopancreatography with sphincter of Oddi manometry and endoscopic sphincterotomy when manometry is abnormal.
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PMID:Outcome after laparoscopic cholecystectomy for chronic acalculous cholecystitis. 945 29


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