The mechanism of the analgesic action of acetaminophen involves the serotonergic system. This study explores how acetaminophen interferes with serotonergic descending pain pathways. Eighteen rapid metabolizers of tropisetron were included in this double-blind cross-over study. After ethical approval, the healthy volunteers took 1 g oral acetaminophen (A) or placebo (p) combined with either the 5-HT3 antagonist tropisetron (T) (5 mg) or saline, intravenously, at weekly intervals. Mechanical pain thresholds, determined before and after a cold pressor test (CPT), were repeated seven times during the three post-dosing hours, and area under the concentration-time curves (AUCs) of the three treatments were compared. After CPT, AUC (%*min) of Ap (1,561+/-429) was larger than before CPT (393+/-382, P<0.05); these effects were totally inhibited by tropisetron. Acetaminophen reinforces descending inhibitory pain pathways; it suggests a supraspinal target for acetaminophen's antinociceptive action. This study also confirmed that there is a central serotonergic mechanism of action for acetaminophen that is not stimulus-dependent.
Price determination theory typically focuses on the role of monetary policy, while the role of fiscal policy is usually neglected. From a different point of view, the Fiscal Theory of the Price Level takes into account monetary and fiscal policy interactions and assumes that fiscal policy may determine the price level, even if monetary authorities pursue an inflation targeting strategy. In this paper we try to test empirically whether the time path of the government budget in EMU countries would have affected price level determination. Our results point to the sustainability of fiscal policy in all the EMU countries but Finland, although no firm conclusions can be drawn about the prevalence of either monetary or fiscal dominance.
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