Pharmacological research : the official journal of the Italian Pharmacological Society
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The present study was designed to investigate the ameliorative potential of rosiglitazone, a peroxisome proliferator-activated receptor gamma (PPAR gamma) agonist, in tibial and sural nerve transection-induced neuropathic pain in rats. The pinprick, cold immersion, hot plate and hot immersion tests were performed to assess the degree of mechanical and cold hyperalgesia; heat hyperalgesia and allodynia, respectively. The tissue thio-barbituric acid reactive species and reduced glutathione were measured as the markers of oxidative stress. ⋯ Administration of rosiglitazone (5 and 10 mg/kg p.o.) attenuated tibial and sural nerve transection-induced mechanical and cold hyperalgesia without modulating heat hyperalgesia. Rosiglitazone also attenuated tibial and sural nerve transection-induced increase in oxidative stress, myeloperoxidase activity and calcium levels. It may be concluded that rosiglitazone has ameliorative potential in attenuating the painful state associated with tibial and sural nerve transection, which may further be attributed to anti-inflammatory actions with subsequent decrease in oxidative stress and calcium levels.
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We determined the role of the dopamine D2 receptor in or adjacent to the dopaminergic A11 cell group in descending modulation of neuropathic hypersensitivity. Moreover, we determined the spinal neurotransmitter receptors mediating the modulatory effect. Neuropathy was produced by spinal nerve ligation in the rat that had a chronic cannula for drug delivery into A11 or a control site in the locus coeruleus, and a catheter for spinal drug delivery. ⋯ Spinal administration of atipamezole (an alpha(2)-adrenoceptor antagonist) or marginally also WAY-100635 (a 5-HT(1A) receptor antagonist), but not raclopride or bicuculline, reduced the antihypersensitivity effect induced by quinpirole in A11. Electrical stimulation of A11 produced thermal antinociception following intrathecal administration of saline but not raclopride. The results indicate that activation of the dopamine D2 receptor in A11 may selectively suppress neuropathic hypersensitivity, due to mechanisms that involve GABA(A) receptors in the hypothalamus and descending noradrenergic pathways acting on spinal alpha(2)-adrenoceptors, possibly together with a slight contribution of descending serotoninergic pathways acting on spinal 5-HT(1A) receptors.
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Irritable bowel syndrome (IBS) is characterized by dysfunction of the afferent pathways that may lead to visceral hypersensitivity. Trimebutine is a weak opioid receptor agonist used in the treatment of IBS. We report on the effects of a novel derivative in which trimebutine has been salified with nitro-arginine(NO2-Arg-Trim), in modulating nociception to colorectal distension (CRD) in intact and post-colitis rats,an animal model that mimics some features of IBS. ⋯ In summary, these data suggest that NO2-Arg-Trim inhibits nociception induced by CRD in both healthy and post-colitis, allodynic rats. The NO2-arginine moiety interacts with the opioid agonist trimebutine to potentiate its analgesic activity. This study provides evidence that NO2-arginine derivative of trimebutine might have beneficial effect in the treatment of painful intestinal disorders.
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Glycyrrhizin is a triterpene glycoside, a major active constituent of licorice (Glycyrrhiza glabra) root and numerous pharmacological effects like anti-inflammatory, anti-viral, anti-tumour and hepatoprotective activities has been attributed to it. In this study we evaluated the anti-inflammatory activities of glycyrrhizin in mice model of acute inflammation, carrageenan-induced pleurisy. We report here that glycyrrhizin (given at 10 mg/kg i.p. 5 min prior to carrageenan) exerts potent anti-inflammatory effects in this model. ⋯ Additionally, we demonstrate that these inflammatory events were associated with the activation of nuclear factor-kappaB (NF-kappaB) and signal transducer and activator transcription-3 (STAT-3) activation in the lung. NF-kappaB and STAT-3 activation were significantly reduced by glycyrrhizin treatment. Taken together, our results indicate that prevention of the activation of NF-kappaB and STAT-3 by glycyrrhizin reduces the development of acute inflammation.
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Randomized Controlled Trial
Ketamine spares morphine consumption after transthoracic lung and heart surgery without adverse hemodynamic effects.
Thoracotomy is associated with severe pain. Large doses of morphine can depress respiratory drive and compromise hemodynamic stability. Ketamine reduces hyperalgesia, prevents opioid tolerance and resistance and lowers morphine consumption. At sub-anesthetic (< or = 500 microg/kg) doses, ketamine rarely produces undesirable hemodynamic alterations. We hypothesized that by combining a sub-anesthetic dose of ketamine with morphine, we could effectively control pain with less morphine and minimize drowsiness, while maintaining safe hemodynamic and respiratory parameters. ⋯ The concomitant use of sub-anesthetic ketamine plus two-thirds the standard MO dose following thoracotomy, MIDCAB or OPCAB resulted in lower pain scores, reduced MO consumption and shorter postoperative IV-PCA dependence. These advantages were associated with cardiovascular stability and even better respiratory parameters.