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)

1. The interactions of three GABAergic compounds, gamma-acetylenic GABA, gamma-vinyl GABA and ethylenediamine with the analgesic effects of morphine and pentazocine were examined in mice using the hot plate and tail immersion tests. 2. A significant increase in reaction time induced by morphine was noted in the tail immersion test after pretreatment with the drugs acting through GABA functions. 3. The inhibitors of GABA transaminase, gamma-acetylenic GABA and gamma-vinyl GABA, and the GABAmimetic ethylenediamine did not significantly change the analgesic action induced by pentazocine. 4. In the hot plate test the three GABAergic compounds antagonized the analgesic effects of pentazocine in contraposition with previous results indicating that morphine-induced analgesia is increased by pretreatment with those agents. 5. These findings suggest that GABAergic and opiopeptidergic systems are interconnected through mu receptors, whereas the kappa opiate systems seem to be unrelated to GABA functions.
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PMID:A comparison of GABAergic influences on the analgesic responses to morphine and pentazocine. 271 13

Ethylenediamine, a GABA receptor agonist induced a small hyperalgesic state in mice, but increased morphine analgesia. The interaction with this morphine effect was not dose-dependent. Ethylenediamine significantly antagonized tolerance development at relatively low doses (5-10 mg/kg). The GABA mimetic agent increased the frequency of abstinence signs in the naloxone-precipitated morphine withdrawal in mice. The effect of ethylenediamine on morphine withdrawal was suppressed by the irreversible GABA transaminase inhibitor, gamma-vinyl GABA.
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PMID:Effects of ethylenediamine on morphine analgesia and tolerance-dependence in mice. 405 78

Effects of valproic acid administration on morphine analgesia and on morphine tolerance and dependence were investigated in mice. Valproate increased the reaction time to thermal stimulation in naive animals. This effect was additive with morphine when valproate was administered shortly before the analgesic. However, an antagonism was observed if a 4-hour period elapsed between valproate and morphine administration. When administered to mice receiving a sustained release preparation of morphine, valproate antagonized the development of tolerance to morphine. Valproate elicited a dual action on the abstinence signs observed after naloxone administration in morphine-treated mice. The effect consisted in a reduction of abstinence behavior if the anticonvulsant was administered a few minutes before naloxone; the same treatment increased the severity of the abstinence behavior when valproate was injected 1 h before the precipitating dose of naloxone. In this latter schedule, concomitant administration of gamma-vinyl-GABA failed to reduce the severity of the convulsions observed during the abstinence syndrome. These results suggest that valproate is metabolized to a compound responsible for decreased analgesia and intensified withdrawal signs.
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PMID:A dual action of valproic acid upon morphine analgesia and morphine withdrawal. 641 Apr 18

In the mouse hot-plate test (50 degrees C), muscimol produced analgesia which was blocked by bicuculline but not by picrotoxin. Analgesia produced by baclofen was dose-dependent and stereoselective, but was not blocked by bicuculline, picrotoxin or naloxone. Morphine-induced analgesia was not altered by bicuculline. The inhibitors of GABA-transaminase, amino-oxyacetic acid, gamma-acetylenic GABA and gamma-vinyl GABA, produced analgesia which was much more prolonged than that observed with muscimol, baclofen or morphine. The analgesic action of these agents was not significantly altered by bicuculline. At a higher plate temperature (55 degrees C), GABA-transaminase inhibitors produced minimal analgesia but significantly enhanced the analgesic action of baclofen. gamma-Vinyl GABA markedly increased both the peak effect and the duration of analgesia but gamma-acetylenic GABA and amino-oxyacetic acid caused smaller increases. In the mouse hot-plate test, bicuculline-sensitive GABA receptors appear to mediate the analgesic action fo muscimol. Analgesia produced by baclofen, morphine and inhibitors of GABA-transaminase may involve another class of GABA receptors which are insensitive to bicuculline.
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PMID:On the involvement of GABA in the analgesia produced by baclofen, muscimol and morphine. 711 May 28

The aim of the present study was to investigate persistent neurobehavioural effects of repeated low-level exposure to chlorphenvinphos ((2-chloro-1-(2,4-dichlorophenyl) vinyl diethyl phosphate-CVP) in rats. The rats received 10 i.p. injections of CVP at daily doses of 0.5 mg/kg or 1.0 mg/kg (one injection/day, five days/week) which corresponded to 1/20 and 1/10 of LD50, respectively, for this species. In a part of the rats, cholinesterase (ChE) activity in blood (plasma and erythrocytes), and in the selected brain regions was determined at arbitrarily chosen time after the last exposure. The determinations showed that the level of ChE inhibition was dose-related, but the compartments studied differed in the magnitude of this effect. The differences in the level of ChE inhibition between the compartments were particularly evident in rats which had received CVP at the 1.0 mg/kg dose; in these animals 3 h after exposure the ChE activity in erythrocytes, plasma and the brain corresponded to 78%, 48% and 67-70%, respectively, of the control value. Enzyme activity returned to the control level after 14 days in plasma and after 35 days in erythrocytes. In rats receiving CVP at daily doses of 0.5 mg/kg, ChE activity in plasma was decreased by 40.8% and that in erythrocytes by 21.4% 3 h after the last exposure. The activity of ChE in plasma returned to the control level within four days and that in erythrocytes within 14 days. In these rats, in all the brain regions studied except brainstem, ChE activity was not reduced significantly. In rats selected for behavioural tests, the following behavioural aspects were investigated: response to novelty in an open field, acquisition and extinction of a one-way active avoidance response, and the magnitude and persistence of the footshock-induced analgesia (hot-plate test). Testing in the open field was performed before the exposure and then 1, 3 and 6 weeks after the last exposure. The remaining tests were performed after the exposure. The interval between testing and the last CVP injection was sufficient for recovery of ChE activity. It has been found that in rats of both exposure groups the response to novelty in the open field, i.e. the increase in locomotor and exploratory activity in the presence of a new object, was reduced, albeit nonsignificantly, compared to the unexposed animals. In rats which received CVP at the dose of 1.0 mg/kg, acquisition of the one-way active avoidance response was facilitated. No differences between groups were found during extinction of this response. In the hot-plate test, in rats exposed repeatedly to 1.0 mg/kg CVP, the footshock-induced increase in the latency of the paw-lick response to heat (54.5 degrees C) was stronger and more persistent than in the unexposed animals. The above results show that some neurobehavioural effects of exposure to organophosphorous (OP) compounds may be detected after a time sufficient for recovery of ChE activity.
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PMID:Long-term behavioural effects of a repeated exposure to chlorphenvinphos in rats. 1046

Appropriate management of post-operative pain is an ongoing challenge in surgical practice. At present, systemic opioid administration is routinely used for analgesia in the post-operative setting. However, due to significant adverse effects and potential for misuse, there is a perceived need for the development of alternative, opioid-sparing treatment modalities. Continuous infusion of local anesthetic into the peritoneum after major abdominal surgery reduces pain and opioid consumption, and enhances recovery from surgery. Here we describe a non-opioid, poly(ethylene-co-vinyl-acetate) intraperitoneal implant for the sustained delivery of local anesthetic following major abdominal surgery. A radio-opaque core had the required mechanical strength to facilitate placement and removal procedures. This core was enclosed by an outer shell containing an evenly dispersed local anesthetic, lidocaine. Sustained release of lidocaine was observed in an ovine model over days and the movement modelled between peritoneal fluid and circulating plasma. While desirably high levels of lidocaine were achieved in the peritoneal space these were several orders of magnitude higher than blood levels, which remained well below toxic levels. A pharmacokinetic model is presented that incorporates in vitro release data to describe lidocaine concentrations in both peritoneal and plasma compartments, predicting similar release to that suggested by lidocaine concentrations remaining in the device after 3 and 7 days in situ. Histological analysis revealed similar inflammatory responses following implantation of the co-extruded implant and a commercially used silicone drain after three days. This non-opioid analgesic implant provides sustained release of lidocaine in an ovine model and is suitable for moving onto first in human trials.
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PMID:A non-opioid analgesic implant for sustained post-operative intraperitoneal delivery of lidocaine, characterized using an ovine model. 3297 58