European journal of pharmacology
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The effects of the kappa-opioid receptor agonist, TRK-820, (-)-17-(cyclopropylmethyl)-3, 14beta-dihydroxy-4, 5alpha-epoxy-6beta-[N-methyl-trans-3-(3-furyl) acrylamido] morphinan hydrochloride, on the itch sensation were compared with those of histamine H1 receptor antagonists, using the mouse pruritogen-induced scratching model. Peroral administration of TRK-820 reduced the numbers of substance P- or histamine-induced scratches dose dependently. No obvious suppression of the spontaneous locomotor activity was observed at the doses used for the experiments, indicating that the inhibition of scratches was not due to the effect on general behavior. ⋯ Histamine H1 receptor antagonists, chlorpheniramine and ketotifen, did not inhibit substance P-induced scratches, or did so only partially. Both antihistamines inhibited the histamine-induced scratches completely. These results suggest that TRK-820 has antipruritic activity which is mediated by kappa-opioid receptors, and is effective in both antihistamine-sensitive and -resistant pruritus.
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Glucocorticoids are the most potent and widely used anti-inflammatory agents, but they are not particularly effective against early phase of acute respiratory distress syndrome. We investigated whether methylprednisolone, a synthetic glucocorticoid, could inhibit increase of phospholipase A(2) activity in the lung and lead to protection against a model of acute respiratory distress syndrome in rabbits. ⋯ Infusion of methylprednisolone (60 mg/kg/h, i.v. for 30 min before the oleic acid and then 0.5 mg/kg/h, i.v. for 6 h) did not improve the above described lung injury induced by oleic acid, nor did it suppress phospholipase A(2) activity and degradation of surfactant in bronchoalveolar lavage fluid, while it strongly reduced interleukin-8 levels in both plasma and bronchoalveolar lavage fluid. We conclude that methylprednisolone did not attenuate oleic acid-induced acute lung injury and this can be explained partly by its failure to reduce the increase of phospholipase A(2) activity and the surfactant degradation in the lung, which might also account for its clinical ineffectiveness against early acute respiratory distress syndrome.
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The effect of noradrenaline in the bed nucleus of the stria terminalis and locus coeruleus on maintenance and reactivation of morphine-conditioned place preference induced by footshock stress was investigated in rats. After receiving alternate injection of morphine (10 mg/kg) and saline for 6 consecutive days, the rats spent more time in the drug-paired compartment (morphine-conditioned place preference) on day 7. These animals did not show morphine-conditioned place preference on day 37 following sham-footshock once every 3 days from days 8 to 36 (28 days drug-free). ⋯ In contrast, chemical lesions of the dorsal noradrenergic bundle that arises from the locus coeruleus had no such effects. These findings suggest that noradrenergic neurons in locus coeruleus are not involved in stress-induced reinstatement of drug-seeking and further clearly demonstrate that noradrenaline in the bed nucleus of the stria terminalis plays a critical role in mediating this effect. Comprehension of the neurochemical events underlying the stress-induced and the bed nucleus of the stria terminalis-mediated reinstatement of drug-seeking may, therefore, throw more light on the biological bases of drug dependence and addictive behavior
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Comparative Study
Hyperbaric oxygen treatment reduces carrageenan-induced acute inflammation in rats.
The present study was designed to assess the anti-inflammatory activity of hyperbaric oxygen treatment by comparing it with that of diclofenac, a nonsteroidal anti-inflammatory drug, and also to investigate whether hyperbaric oxygen treatment enhances the anti-inflammatory effect of diclofenac in carrageenan-induced paw edema which is commonly employed as an acute inflammation model in rats. Hyperbaric oxygen treatment and diclofenac (20 mg/kg) markedly reduced the carrageenan-induced paw edema in rats. In other words, they displayed anti-inflammatory activity. On the other hand, hyperbaric oxygen treatment did not consistently modify the anti-inflammatory effect of diclofenac in this model.
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This study was designed to determine (1) whether chronic amitriptyline administration was effective in alleviating symptoms of neuropathic pain in a rat model of spinal nerve injury, and (2) whether the effect of amitriptyline involved manipulation of endogenous adenosine, by determining the effect of caffeine, a non-selective adenosine A(1) and A(2) receptor antagonist, on its actions. Nerve injury was produced by unilateral spinal nerve ligation of the fifth and sixth lumbar nerves distal to the dorsal root ganglion, and this resulted in stimulus-evoked thermal hyperalgesia and static tactile mechanical allodynia. Animals received pre- and post-surgical intraperitoneal doses of amitriptyline (10 mg/kg) and caffeine (7.5 mg/kg), alone or in combination, and following surgery, were administered amitriptyline (15-18 mg/kg/day) and caffeine (6-8 mg/kg/day), alone or in combination, in the drinking water. ⋯ The results of this study indicate that chronic administration of amitriptyline is effective in alleviating thermal hyperalgesia, but not static tactile allodynia, in the hindpaw ipsilateral to nerve injury, and the block of this effect by caffeine suggests that this effect is partially achieved through manipulation of endogenous adenosine systems. Additionally, chronic amitriptyline administration induces contralateral hyperaesthetic responses that are augmented by caffeine. Both the symptom-specific effect, and adenosine involvement in amitriptyline action may be important considerations governing its use in neuropathic pain.