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)

Acute swim stress of mice produces increases in the density of high and low affinity binding sites in the brain for the inhibitory neurotransmitter gamma-aminobutyric acid (GABA), together with analgesia as measured by an increase in tail flick latency. Apparent tolerance develops in repeated swimming with analgesia and GABA binding returning towards control levels. The time course of analgesia and increases GABA binding following a single swim are also similar. Acute swim stress does not alter diazepam binding. GABA systems may be important in analgesia and in responses to environmental stress.
 ...
PMID:Increased GABA binding in mouse brain following acute swim stress. 626 80

The current study was conducted in order to explore the effects of repeated naloxone administration as a function of food intake. Rats were trained to press a bar to avoid foot-shock. They were allowed either free or restricted access to food. Free-feeding rats developed a strong sensitivity to naloxone, as manifested by an increased shock rate after naloxone injection. When animals were food-deprived, the sensitivity was greatly reduced. A different species (mouse) and two different tests were used to examine further the effects of food intake and pretreatment with naloxone. The mice were given either free access to food or a restricted diet and were pretreated with either naloxone or saline. The effects of food intake and pretreatment with naloxone were examined in terms of motor activity, morphine analgesia and naloxone hyperalgesia. The results showed that prior exposure to naloxone in free-feeding animals enhanced the suppressant effect of naloxone on motor activity and the analgesic effects of morphine (as measured by paw-lick, but not as measured by jump in the hot-plate test), but had no effect on the hyperalgesic effect of naloxone. When mice were food-deprived during naloxone administration, sensitization did not occur. The hypothesis that naloxone sensitivity is due to changes in the number of brain opiate receptors was tested by measuring the number and affinity of [3H]naloxone binding sites on brain membranes from mice chronically treated with naloxone. Neither naloxone pretreatment nor food deprivation affected the number or affinity of binding sites. The gamma-aminobutyric acid antagonist effect of naloxone (as measured by gamma-[3H]aminobutyric acid binding) was also unchanged by naloxone pretreatment. Thus, the basis of the interactions between naloxone and the feeding state remains unclear.
 ...
PMID:Sensitization produced by repeated administration of naloxone is blocked by food deprivation. 628 15

It has been shown in experiments on an isolated spinal cord of rats that morphine, serotonin and gamma-aminobutyric acid (GABA) induce the depolarization of the central terminals of primary afferents. The depolarizing effect of morphine is mediated via interneurons, while the similar effect of serotonin and GABA is the result of a direct action on primary afferents. Subarachnoidal injection of morphine (0.1-0.6 mg), serotonin (0.1-0.3 mg) and GABA (0.3-0.6 mg) provokes analgesia upon electric stimulation of the tail root in rats.
 ...
PMID:[Subarachnoid analgesia induced by serotonin and gamma-aminobutyric acid]. 668 92

The analgesic effect of morphine was antagonized in mice by intracerebroventricular pretreatment with taurine, gamma-aminobutyric acid (GABA) or glycine and was potentiated by ethylene glycol tetra-acetic acid (EGTA) but not altered by L-glutamate or L-aspartate. The potentiation of morphine analgesia by EGTA was reversed by a concentration of taurine that did not alter the tail-flick response. The selective depletion of 45Ca2+ from synaptic vesicles observed with morphine administration was significantly inhibited by taurine injection (1.2 mumol/brain, i.vt.) but was not altered by the same dose of GABA. Inhibition of ATP-dependent 45Ca2+ uptake in synaptosomes by morphine was also completely reversed by taurine (10(-2)M which by itself did not alter 45Ca2+ uptake. These results suggest that antagonism of morphine analgesia by taurine may be caused by blockade of the morphine-induced inhibition of both ATP-dependent synaptosomal 45Ca2+ uptake and changes in synaptic vesicular 45Ca2+ localization, while the antagonism by GABA was not associated with synaptosomal Ca2+.
 ...
PMID:Effects of amino acids, especially taurine and gamma-aminobutyric acid (GABA), on analgesia and calcium depletion induced by morphine in mice. 678 72

Both the gamma-aminobutyric acid (GABA) mimetic, THIP (4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol and the serotonergic agonist, MK 212 (6-chloro-2[ 1-piperazinyl ]pyrazine) are effective analgesic agents in the mouse hot plate assay. Naltrexone, however, fails to reverse the analgesia elicited by either compound. Acute injection of THIP potentiates the morphine analgesia and chronic administration of THIP produces a functional tolerance to its analgesic effects. MK 212 antagonizes the analgesia induced by either morphine or THIP. These results support the postulate that GABAergic and serotonergic synapses represent two synaptic mechanisms which participate in the modulation of pain threshold in a manner that is independent from opioid receptors. Moreover, GABA and serotonin appear to be able to modulate opioid-mediated analgesia in an opposing manner with GABAergic mechanisms facilitating and serotonergic mechanisms inhibiting morphine-induced antinociception.
 ...
PMID:A comparison of the analgesic activities of 4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol (THIP) and 6-chloro-2[1-piperazinyl]pyrazine (MK 212). 687 80

Agonists and antagonists of gamma-aminobutyric acid, i.e. GABAergic drugs, such as muscimol, baclofen or bicuculline, alone or in combination, exhibited analgesic effects per se and enhanced the analgesia induced by morphine. The analgesic effects of GABAergic drugs were unaffected by administration of naloxone in a dose which antagonized the analgesia induced by morphine. The ED50 for the antinociceptive effect of muscimol, bicuculline, picrotoxin, gabaculline or aminooxyacetic acid (AOAA) was not affected in the morphine-tolerant group as compared to the control group, in contrast to the increase in the ED50 for morphine under similar conditions; this indicated that there was no development of cross-tolerance between morphine and GABAergic drugs. Muscimol suppressed the abrupt withdrawal-jumping induced by morphine and enhanced the suppression of this phenomenon by morphine. The GABAergic drugs also shared with morphine the property of inhibiting gastrointestinal (GIT) motility. Naloxone reversed the inhibition of motility induced by morphine but failed to influence that induced by GABAergic drugs. In the morphine-tolerant state, the sensitivity of gastrointestinal motility to morphine decreased, whereas, the sensitivity to GABAergic drugs remained unaltered. The results indicate that GABAergic drugs share some of the classical properties of morphine, such as analgesia and inhibition of gastrointestinal motility, but they probably do so by different mechanisms.
 ...
PMID:GABAergic drugs, morphine and morphine tolerance: a study in relation to nociception and gastrointestinal transit in mice. 688 70

Effects of taurine or gamma-aminobutyric acid (GABA) on akinesia and analgesia induced by D-Ala2-Met-enkephalinamide were investigated in rats. Administration of taurine (dose range: 2.375 X 10(-2) M-9.5 X 10(-2)-Met-enkephalinamide were investigated in rats. Administration of taurine (dose range: 2.375 X 10(-2) M-9.5 X 10(-2) M/10 microliters) into the left lateral ventricle 10 min prior to the injection of D-Ala2-Met enkephalinamide (50 microgram/10 microliter) produced a dose-dependent reduction in the duration of akinesia and to some extent of analgesia, as estimated at 30 min and 60 min following the enkephalinamide injection; at the first estimation-time (10 min), taurine did not alter the duration of akinesia or that of analgesia. The median effective dose (ED50) for akinesia determined at 60 min after D-Ala2-Met-enkephalinamide was 5 times greater and that for analgesia assessed at the same time was 1.7 times greater in taurine-treated rats than the respective doses in control animals. Administration of GABA under similar experimental conditions produced a dose-dependent reduction in the duration of analgesia from the initial estimation time (10 min) following the injection of D-Ala2-Met-enkephalinamide. The ED50 for analgesia determined at 30 min after D-Ala2-Met-enkephalinamide was 3 times greater in GABA-treated rats than in control animals. Unlike the effects of taurine, GABA did not alter the duration of akinesia. Neither the duration of akinesia nor that of analgesia was modified by taurine or GABA alone in rats tested 9 min after the injection of each amino acid. These findings suggest that taurine may promote a recovery from both akinesia and analgesia, while GABA decreases only the analgesia induced by D-Ala2-Met-enkephalinamide.
 ...
PMID:Effects of taurine and gamma-aminobutyric acid on akinesia and analgesia induced by D-Ala2-Met-enkephalinamide in rats. 724 12

Injection of formalin into the hindpaw of a rat induces a biphasic response in pain-related behaviours, such that C-fibre activation during phase 1 triggers a state of central sensitization characterized by a longer lasting phase 2. As the inhibitory neurotransmitter gamma-aminobutyric acid (GABA) may participate in processing of nociceptive inputs, we hypothesized that pentobarbitone and propofol, i.v. anaesthetics with known GABAA agonist properties, would interfere with development of central sensitization and thereby modify the phase 2 hyperalgesic response. Pentobarbitone administered i.v. before injection of formalin produced dose-dependent suppression of phase 2, even though animals had recovered from anaesthesia, whereas it had substantially less effect when given after phase 1 had resolved. Picrotoxin, a GABAA antagonist, reversed the effect of pentobarbitone on phase 2 pain behaviour but was itself a mild analgesic. In contrast, propofol had no effect on phase 2 formalin-induced pain behaviour. Thus we conclude that pentobarbitone, but not propofol, produced pre-emptive analgesia in this model, presumably by suppressing noxious stimulation-induced central sensitization via activation of GABAA receptors.
 ...
PMID:Pentobarbitone, but not propofol, produces pre-emptive analgesia in the rat formalin model. 802 13

We examined the interactions of D,L-laudanosine, a potentially epileptogenic metabolite of the neuromuscular relaxant atracurium besylate, with gamma-aminobutyric acid (GABA) and opioid binding sites, all of which have been implicated in seizure activity. Laudanosine was almost ineffective at [3H]muscimol binding to high-affinity GABA receptors (IC50 = 100 microM). However, laudanosine displayed an inhibitory effect at the low-affinity GABA receptors labeled by [3H]bicuculline methochloride, with an IC50 value of 10 microM. At the opioid receptor subtype, laudanosine lowered radiolabeled opioid binding at the mu 1, mu 2, delta, kappa 1, and kappa 3 receptors with Ki values of 2.7, 13, 5.5, 21, and 24 microM, respectively, concentrations seen clinically in blood and approaching those measured in cerebrospinal fluid. Saturation studies of mu 1, mu 2, delta, and kappa 3 sites in the presence of laudanosine revealed competitive interactions, with increases in the apparent Kd values but without significant changes in the maximal numbers of binding sites. In addition, we investigated whether the in vitro laudanosine-opioid receptor interaction would also be expressed by analgesic physiologic effects. We found that laudanosine elicited a dose-dependent analgesia in mouse tail-flick assay that was attenuated by coadministration of beta-funaltrexamine (mu 1- and mu 2-selective antagonist) and of naloxonazine (mu 1 antagonist), but not by nor-binaltorphimine (kappa 1-selective antagonist) or naltrindole (delta-selective antagonist), indicating a mu 1 mechanism for analgesia-mediated property of laudanosine. There is evidence suggesting mu 2 activity as well, but this is due to the ability of laudanosine to elicit analgesia when given intrathecally. We also observed cross-tolerance between laudanosine and morphine, as well as a partial effect of laudanosine on gastrointestinal transit. These results suggest an interaction between laudanosine and the low-affinity GABA receptor, as well as opioid mu 1 and mu 2 receptors.
 ...
PMID:Interactions between laudanosine, GABA, and opioid subtype receptors: implication for laudanosine seizure activity. 806 69

Pregnancy is associated with an increased sensitivity to both general and local anesthetics. The exact reason is uncertain, but increased concentrations of progesterone and endogenous opiates have been implicated. Therefore, we tested the ability of intrathecally administered progesterone to produce analgesia and to potentiate the effects of spinal sufentanil. Female rats had intrathecal catheters implanted for drug administration, and analgesia was measured using the tail flick assay or hemostat clamp test. Animals were pretreated first with 10 micrograms, 20 micrograms, or 40 micrograms of intrathecal progesterone (n = 5, for each dose) and then given a minimally analgesic dose of sufentanil. Pretreatment with progesterone potentiated sufentanil's effect and resulted in almost complete analgesia. In contrast, in animals not pretreated with progesterone, the same dose of sufentanil resulted in minimal analgesia (n = 15). Intrathecal progesterone alone had no analgesic effects. No behavioral or motor effects were noted after progesterone treatment. Cerebral spinal fluid progesterone levels were within physiologic range. Furthermore, 100 micrograms of progesterone administered intramuscularly did not potentiate sufentanil analgesia. A major progesterone metabolite, 5 alpha-pregnane-3 alpha-ol-20-one, 5 micrograms, 10 micrograms, or 20 micrograms (n = 5, for each dose), also potentiated sufentanil analgesia when administered intrathecally. In contrast, a stereoisomer, 5 beta-pregnane-3 beta-ol-20-one failed to show potentiation. Finally, two drugs that block gamma-aminobutyric acid-mediated increases in chloride ion conductance, picrotoxin and bicuculline, each blocked progesterone-mediated potentiation of sufentanil analgesia.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Progesterone-mediated potentiation of spinal sufentanil in rats. 846 10


<< Previous 1 2 3 4 5 6 7 Next >>