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)

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.
 ...
PMID:Reversal of electroacupuncture tolerance by CCK-8 antiserum: an electrophysiological study on pain-related neurons in nucleus parafascicularis of the rat. 822 97

It has been reported that intrathecal (i.t.) injection of CCK-8 showed a marked antagonism to analgesic effects mediated by mu-opioid receptors in rat. The present study was performed to ascertain whether the blockade of endogenously released CCK-8 by potent and selective CCK-A antagonist devazepide and CCK-B antagonist L-365260 would affect opioid analgesia at the spinal cord level. A marked potentiation of the analgesic effect induced by morphine (4 mg/kg, sc) was produced by i.t. injection of 100 ng devazepide or 2.5 ng L-365260. Dose-response curves for the enhancement of the two drugs on morphine analgesia were bell-shaped. Intrathecal injection of 66 ng devazepide or 1.25 ng L-365260 was also shown to potentiate the analgesic effect induced by the selective mu-opioid agonist ohmefentanyl (OMF) (32 ng, i.t.). The dose-response curves were also bell-shaped. Devazepide or L-365260 per se produced no significant changes in rat tail flick latency (TFL). The above results are interpreted to mean that endogenously released CCK-8 in the spinal cord plays an antagonistic role to opioid analgesia, and it is the CCK-B receptors that mediate the anti-opioid effect since the dose of devazepide is 40-50 times higher than that of L-365260.
 ...
PMID:[Potentiation of morphine- and ohmefentanyl-induced analgesia by cholecystokinin receptor antagonists in rat]. 823 25

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.
 ...
PMID:Non-opioid peptides for analgesia. 831 62

This is the first report showing, in an in vivo study, that systemic morphine produced a marked (89%, P < 0.01) increase of the cholecystokinin octapeptide (CCK-8) immunoreactivity in the perfusate of the rat spinal cord, an effect completely reversed by naloxone. Since CCK-8 has been shown to possess potent anti-opioid activity at a spinal level, a blockade of the spinal cholecystokinin effect would be expected to potentiate opiate analgesia. With tail flick latency as a nociceptive index, it was found that intrathecal (i.t.) injection of a novel CCKB antagonist L-365,260 produced a marked potentiation of the analgesic effect induced by the mu-opioid agonists morphine (4 mg/kg s.c.) or ohmefentanyl (32 ng i.t.). Similar effects were obtained with the CCKA antagonist devazepide at a dose 40-50 times higher than that of L-365,260. Both devazepide and L-365,260 showed a bell-shaped dose-response curve. The results confirm the notion that an increased release of CCK-8 may constitute a self-limiting process for opioid effects at the spinal level, and that it is the CCKB receptor which mediates the anti-opioid effect of CCK-8 in the rat spinal cord.
 ...
PMID:Increased release of immunoreactive cholecystokinin octapeptide by morphine and potentiation of mu-opioid analgesia by CCKB receptor antagonist L-365,260 in rat spinal cord. 838 8

Cholecystokinin octapeptide (CCK-8) in CNS has been shown to function as a neuropeptide with potent anti-opioid activity. It hinders opioid analgesia and facilitates opioid tolerance. The present study showed that electroacupuncture (EA) stimulation produced a marked increase of the CCK-8 immunoreactivity (ir) in the perfusate of the rat spinal cord. The increase of CCK-8-ir was most marked in response to EA of 100 Hz and 15 Hz, and less marked in response to EA of 2 Hz. Since CCK-8 has been shown to possess potent anti-opioid activity at the spinal level, blockade of the spinal CCK effect would be expected to potentiate EA-induced analgesia which is known to be opioid-mediated. Intrathecal (i.t.) administration of CCK-B antagonist L-365,260 per se did not affect tail flick latency (TFL) to any significant extent, yet it potentiated EA induced analgesia in a dose- and frequency-dependent manner. The potentiation was most marked at a dose range of 2.5-5.0 ng (i.t.) and at a frequency rank order of 100 Hz > 15 Hz > 2 Hz. The results suggest that an increased release of CCK-8 following EA may limit the effect of opioid peptides, and that the CCK-B receptor mediates the anti-opioid effect of CCK-8 in rat spinal cord.
 ...
PMID:Increased release of immunoreactive CCK-8 by electroacupuncture and enhancement of electroacupuncture analgesia by CCK-B antagonist in rat spinal cord. 847 32

Extracellular single unit recordings were made from spinal dorsal horn wide dynamic range neurons in spinal transected, urethane-anesthetized rats. The unit discharges elicited by noxious electrical stimulation of the hind paw were suppressed by electroacupuncture (15 Hz, 0.3 ms, 3 mA, 30 min) placed at the hind leg points (S-36 and SP-6). Local spinal superfusion with naloxone (20 micrograms/15 microliters) or CCK-8 (10 ng/15 microliters) attenuated, whereas CCK-B receptor antagonist L365,260 (2.5 micrograms/15 microliters) enhanced the electroacupuncture effect. These findings provide further evidence for the notion that CCK-8, in the spinal cord, functions as an antiopioid substrate that antagonizes opioid- or electroacupuncture-induced analgesia.
 ...
PMID:Cholecystokinin octapeptide reverses the inhibitory effect induced by electroacupuncture on C-fiber evoked discharges. 888 94

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.
 ...
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

Several analogs of Boc-protected C-terminal heptapeptide of cholecystokinin (Boc-CCK-7) with modified C-end Phe were pharmacologically characterized. The influence of the number of methyl groups on aromatic side chain of Phe was investigated in following tests: binding to pancreatic and brain membrane receptors, gall bladder contraction, amylase secretion, anorexia, sedation and analgesia. Two analogs seem to be promising selective anorectic agents with strongly protracted effect: Boc-[Phe(triMe)7]CCK-7 and Boc-[Phe(pentaMe)7]CCK-7. The first analog exhibits the same spectrum of activities as CCK-8, however partially decreased central effects, the second one shows partially decreased peripheral activities and totally suppressed central ones. Our study supports the idea that C-terminal residue of CCK is more important for biological potency than for binding to CCK receptors.
 ...
PMID:Cholecystokinin analogs with suppressed central activities. 949 62

The aim of this paper is to study the synergistic anti-analgesic effect of angiotensin II (Ang II) plus cholecystokinin octapeptide (CCK-8). Our previous studies have shown that both CCK-8 and Ang II are potent anti-opioid substances. Intracerebroventricular (i.c.v.) injection of CCK-8 or Ang II dose-dependently antagonizes morphine-induced analgesia (MIA). In the present study, we observed the combined effect of CCK-8 and Ang II in antagonizing MIA. CCK-8 and Ang II were injected intracerebroventricularly to rats in various proportions and doses. The results were analyzed with isobolographic analysis. Combined injection of CCK-8 and Ang II in a ratio of 1 ng: 2.5 microg or 1 ng: 5 microg produced significantly greater effect in antagonizing MIA. The ED(50) of the two ratios are only 18.5% and 27.5%, respectively, of the theoretical dose of simple addition. We conclude that CCK-8 and Ang II used in such dose ratios may antagonize MIA synergistically.
 ...
PMID:Synergistic effect of cholecystokinin octapeptide and angiotensin II in reversal of morphine induced analgesia in rats. 1078 20

The discovery that the endogenous morphine-like peptides named enkephalins are inactivated by two metallopeptidases, neutral endopeptidase and aminopeptidase N, which can be blocked by dual inhibitors, represents a promising way to develop 'physiological' analgesics devoid of the side effects of morphine. A new series of dual aminophosphinic inhibitors of the two enkephalin-catabolizing enzymes has been recently designed. In this study, one of these inhibitors, RB3007, was tested in various assays commonly used to select analgesics (mouse hot-plate test, rat tail-flick test, writhing and formalin tests in mice, and paw pressure test in rats), and the extracellular levels of the endogenous enkephalins in the ventrolateral periaqueductal grey have been measured by microdialysis after systemic administration of RB3007. In the mouse hot-plate test, the dual inhibitor induced long-lasting (2 h) antinociceptive effects with a maximum of 35% analgesia 60 min after i.v. or i.p. administration. These antinociceptive responses were antagonized by prior injection of naloxone (0.1 mg/kg, s.c.). Similar long lasting effects were observed in the other animal models used. Very interestingly, injection of RB3007 (50 mg/kg, i.p.) significantly increased (82%) the extracellular levels of Met-enkephalin with a peak 60 min after i.p. injection. This increase parallels the antinociceptive responses observed. In addition, strong facilitatory effects of subanalgesic doses of the CCK(2) receptor antagonist, PD-134,308 or the synthetic opioid agonist, methadone on RB3007-induced antinociceptive responses were observed. These findings may constitute promising data for future development of a new class of analgesics that could be of major interest in a number of severe and persistent pain syndromes.
 ...
PMID:Pain management by a new series of dual inhibitors of enkephalin degrading enzymes: long lasting antinociceptive properties and potentiation by CCK2 antagonist or methadone. 1285 23


<< Previous 1 2 3 4 5 6 Next >>