Pharmacology
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The rewarding effects of drugs of abuse are often studied by means of the conditioned place preference (CPP) paradigm. CPP is one of the most widely used models in behavioral pharmacology, yet its theoretical underpinnings are not well understood, and there are very few studies on the methodological and theoretical aspects of this model. An important drawback of the classical CPP paradigm is that it often does not show dose-dependent results. ⋯ These findings suggest that the use of an extinction paradigm can extend the quantitative assessment of the rewarding effect of drugs - however, within certain limits only. The present paradigm appears to be less suited for comparing the rewarding efficacy of different drugs due to great test-retest variability. Finally, the additional potential gain of information using this paradigm has to be weighed against the considerably large amount of additional time and effort.
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Recently, paeoniflorin (PF) administered systemically was found to have analgesic effects against inflammatory pain and hypersensitivity in a naloxone-reversible manner. In the present study, we adopted intrathecal administration to evaluate whether PF has direct antinociceptive actions at the spinal level. Pain-related behaviors and spinal c-Fos expression were induced by subcutaneous injection of bee venom (BV) into one hind paw of a rat. ⋯ We further evaluated the intrathecal effects of the drug on the BV-induced c-Fos expression. The result showed that intrathecal PF preconditioning was effective to suppress spinal c-Fos expression in both superficial (lamina I-II) and deep (lamina IV-VI) layers of the L(4-5) dorsal spine. This result showed that PF has a direct pharmacological action in the spinal cord dorsal horn via activation of opioid receptors.
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Comparative Study
Analgesic and antiallodynic effects of antidepressants after infiltration into the rat.
Tricyclic antidepressants (TCA) have potent local anesthetic properties and may produce a long-lasting pain blockade that could be of interest in relieving chronic pain states such as neuropathic pain, but there are only few data comparing their dose-response curves of analgesic activity under the same experimental conditions. This study examines the time course of pain-relieving properties of 7 TCA in heat-induced paw withdrawal after subcutaneous administration. Mixed inhibitors of norepinephrine and serotonin uptake (amitriptyline, nortriptyline, imipramine, desipramine, doxepin) and selective inhibitors of serotonin uptake (fluoxetine and fluvoxamine) were assayed. ⋯ The antiallodynic effect always lasted less long than the analgesic effect. These observations provide support for the potential use of TCA as durable analgesics. Doxepin overall showed the most outstanding results in pain relief.
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This study aimed to elucidate the role of T-type calcium channels in the nociceptive signal transmission at the spinal level. The chronic compression of dorsal root ganglion (CCD) rat model was adopted. Three doses (50, 100 and 200 microg in groups Mib50, Mib100 and Mib200, respectively) of specific T-type Ca2+ channel inhibitors mibefradil (Mib) or normal saline (NS) were intrathecally administered on the 5th day after the CCD model had been established. ⋯ However, only Cav3.2 and Cav3.3 T-type calcium channel mRNA were detected in the lumbar spinal cord of rats, and there were no Cav3.1 calcium channels. Compared with native and sham groups, the Cav3.2 and Cav3.3 calcium channel mRNA expression increased significantly (p < 0.05). These data support the view that spinal T-type calcium (Cav3.2 and Cav3.3 but not Cav3.1) channels may play an important role in the pathogenesis of neuropathic pain.
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Comparative Study
Effects of hydroxyethyl starch, gelatin and dextran on endothelium-derived relaxation in porcine coronary arteries.
In a pilot study we could show that hydroxyethyl starch (HES) induced a significant reduction of endothelium-dependent relaxation (EDR) and the endothelium-derived hyperpolarizing factor (EDHF). In this follow-up study we investigated whether this effect of HES was dose-dependent and whether it could be replicated with other colloids like dextran (DX) and gelatin (GL). ⋯ For clinically relevant concentrations of HES, DX and GL a significant reduction in both NO-induced and NO-/prostacyclin-independent EDR can be found in epicardial coronary arteries of the pig.