Clinical and experimental pharmacology & physiology
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Clin. Exp. Pharmacol. Physiol. · May 2007
CB1 receptor activation in the basolateral amygdala produces antinociception in animal models of acute and tonic nociception.
1. Recent studies have suggested that the basolateral nucleus of the amygdala (BLA) participates in the processing of pain information, especially noxious somatic information. Cannabinoid receptors or CB1 mRNA are expressed more in the BLA than in other nuclei of the amygdala. ⋯ Administration of the CB1 receptor antagonist AM251 (0.55, 5.5, or 55.5 ng/side) alone did not alter the nociceptive thresholds in either test. Bilateral microinjection of the selective CB2 receptor antagonist N-[(1S)-endo-1,3,3-trimethyl bicyclo [2.2.1] heptan-2-yl]-5-(4-chloro-3-methylphenyl)-1-(4-methylbenzyl)-pyrazole-3-carboxamide (SR144528; 1 microg/side) had no effect on the antinociception produced by WIN 55,212-2, suggesting that the antinociceptive actions of WIN 55,212-2 are mediated by CB1 receptors. 4. The findings suggest the existence of a CB1-mediated inhibitory system in the BLA that, when activated, can diminish responsivity to acute and tonic noxious stimuli, but that normally has no tonic effect on the response threshold of these stimuli.
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Clin. Exp. Pharmacol. Physiol. · May 2007
Studies with ketamine and alfentanil following Freund's complete adjuvant-induced inflammation in rats.
1. N-Methyl-D-aspartate (NMDA) receptor antagonists suppress inflammatory hyperalgesia and the development of acute opioid tolerance. They may also enhance opioid-induced antinociception, while suppressing postopioid-induced hyperalgesia and opioid-enhanced inflammatory hyperalgesia. 2. ⋯ These findings complement previous studies in which non-competitive NMDA receptor antagonists suppressed behavioural hyperalgesia. 7. However, racemic and (S)-ketamine did not further enhance alfentanil's antinociceptive effects, although they appeared to prolong alfentanil's antinociceptive effects in the non-inflamed hind paw. These findings suggest that factors such as time-course, frequency and the mode of administration of NMDA receptor antagonists, in addition to the type of antinociceptive model (i.e. inflammatory compared with acute) and the nociceptive testing procedure (i.e. noxious mechanical compared with low threshold stimuli) may influence their effects on opioid-induced antinociception.
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Clin. Exp. Pharmacol. Physiol. · Jan 2007
Effects of hyperbaric oxygen on glucose, lactate, glycerol and anti-oxidant enzymes in the skeletal muscle of rats during ischaemia and reperfusion.
1. Hyperbaric (HBO(2)) and topical oxygen represent two accepted options to oxygenate tissues. The aim of the present study was to investigate the effect of HBO(2) on energy metabolism and anti-oxidant enzymes in a rat model of ischaemia-reperfusion (IR) skeletal muscle injury. 2. ⋯ Catalase activity and MDA increased significantly after 1 h of reperfusion. The HBO(2) attenuated the reperfusion-induced increase in CAT activity and MDA. 6. The results of the study suggest that HBO(2) may have some beneficial effect by decreasing lactate and glycerol levels and modulating anti-oxidant enzyme activity in postischaemic skeletal muscle in our rat model of tourniquet-induced IR skeletal muscle injury.
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Clin. Exp. Pharmacol. Physiol. · Jan 2007
The specific free radical scavenger edaravone suppresses bleomycin-induced acute pulmonary injury in rabbits.
1. Intratracheal instillation of bleomycin induces a condition in rabbits that serves as a useful model of human pulmonary fibrosis. Bleomycin-induced production of reactive oxygen species leads to acute lung inflammation and induction of apoptosis, which is followed by pulmonary fibrosis at a later chronic stage. ⋯ In addition, significantly increased numbers of TUNEL-positive (apoptotic) and transforming growth factor-beta-positive cells were seen. All these effects were significantly attenuated by treatment with edaravone. 4. The findings of the present study suggest that edaravone may be useful in the prevention of acute lung injury resulting from the production of reactive oxygen species.
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Clin. Exp. Pharmacol. Physiol. · Jan 2007
Interactions between metoclopramide and morphine: enhanced antinociception and motor dysfunction in rats.
1. Opioid analgesics and anti-emetics are often used concomitantly to treat pain and nausea and vomiting in people with malignant disease. We investigated interactions between the opioid analgesic morphine and the anti-emetic metoclopramide, a dopamine D2 receptor antagonist, on nociception and gross motor function. 2. ⋯ Only the high dose of metoclopramide compromised running performance when administered with saline. However, coadministering morphine with metoclopramide (both doses) decreased motor performance. 5. Therefore, metoclopramide, possibly through its actions on D2 receptors and not 5-HT(3) receptors, enhances the analgesic and antihyperalgesic effects of morphine, but morphine exacerbates metoclopramide-induced motor dysfunction in rats.