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Pain is an unpleasant sensation that causes mild or severe physical discomfort, by which induces the use of analgesics which are basically of two types: opioids or NSAIDs. The objectives of the present study was to evaluate the antinociception activity induced by NSAIDs and opioids in a thermal model of animal pain, the tail flick assay, and to determine the effect of the MOR antagonist, naltrexone. Antinociception was assessed by the tail flick test using an digital algesiometer. The rank orden of potency was fentanyl > morphine > ibuprofen > tramadol > codeine > meloxicam > paracetamol and the antinociceptive ratio, compared with paracetamol, was between 460 for fentanyl and 1 for meloxicam.Pretreatment with the opioid receptor antagonist, naltrexone, 1 mg/kg i.p., significant reversed the antinociceptive effect of NSAIDs and opioids. The results obtained with naltrexone in this assay confirm the antagonism of this agent on opioids. However, the antagonism over NSAIDs is a new finding since that has not been previously reported. This study test that NSAIDs and opioids induce antinociceptive activity in a thermal murine phasic pain with the following rank orden of potency fentanyl > morphine > ibuprofen > tramadol > codeine > meloxicam > paracetamol. Although the mechanisms of action of these drugs are different, naltrexone, a MOR antagonist, blocked the effects of both agents, suggesting that inhibition of pain seem partially mediated by MOR with association to central mechanisms.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are often used in the treatment of pain. In this study was evaluated, by isobolographic analysis, in a radiant heat model of mice, the tail flick, the potential antinociceptive pharmacological interaction of the combination between ketorolac and meloxicam and the modulation by tropisetron, risperidone, prazosin, yohimbine, naltrindole or 7-Nitroindazole. In the assay, the combination of ketorolac with meloxicam induces an additive interaction with an interaction index of 12.20 ± 0.92. Neither tropisetron nor risperidone nor prazosin nor yohimbine modify the nature of interaction, however naltrindole and 7-Nitroindazol change the nature of interaction from additive a subadditive with an interaction index of 16.85 ± 2.52 and 18.00 ± 2.57, respectively. The current results suggests that the interaction antinociceptive of the combination between ketorolac with meloxicam does not seem to be influenced by adrenergic, dopaminergic, histaminergic or serotonegic mechanisms. Nonetheless, the pretreatment of the mice with naltrindole or con 7-Nitroindazole induced a significant decrease in the antinociceptive power of the combination with a significant reduction in DE. It is suggested that DOR and NO may be involved, in the tail flick model, regulating the antinociceptive bioactivity of these NSAIDs.

The analgesic activity of tramadol has been recognized both in man and in several animal models of pain. However an extensive characterization of the opioid mechanism of action of tramadol of pain has not been reported. The objective of the present study was to evaluate the antinociceptive and anti-inflammatory activity of tramadol in different animal pain models and to determine the effect of the selective opioid antagonist: naltrexone, naltrindole and nor-binaltorphimine. The i.p. administration of tramadol induced a dose-dependent with the following order of potency: formalin hind paw, phase II > formalin hind paw, phase I> acetic acid writhing > tail flick > hot plate. Pretreatment of the mice with naltrexone (1 mg/kg i.p.) antagonized tramadol activity in the acetic acid writhing test, in the hot plate and the tail flick assays, however lack of effect in the formalin hind paw assays. Naltrindole (1 mg/kg i.p.) did not induce a significant change in all the murine assays. However, the mice pretreated with nor-binaltorphimine (1 mg/kg, i.p.) did not modified the tramadol antinociception in the acetic acid writhing and in the hot plate assays. Besides, nor-binaltorphimine pretreatment reversed significantly the tramadol effect in the tail flick and in the formalin hind paw assays. This findings suggests that tramadol effect is mediated by MOR and KOR rather DOR receptors.

Background: Endothelial dysfunction is associated to a lower production of nitric oxide and a reduction of endothelium mediated vasodilation. Aim: To study the effects of pharmacological agents that modify nitric oxide synthetase (NOS) activity on tension changes induced by phenylephrine in rings of internal mammary and radial arteries and saphenous vein. Material and methods: Vessel rings of 7 to 10 mm length were obtained from 32 patients subjected to coronary vascular surgery Fourteen samples of radial artery, 12 samples of internal mammary artery and 15 samples of saphenous vein were obtained. A maximal contraction was induced with KC1 and dose response curves for phenylephrine (FE) in the absence or presence of L-arginine and L-arginine methyl ester (L-NAME), were constructed. Results: The tension induced by FE in internal mammary artery and saphenous vein reached a maximum, near 90% of 80 mM KCl-induced contraction, but in the radial artery, it reached a maximum of 63% (p