ラットのホルマリン誘発炎症性疼痛における末梢 5-HT_<2A> 受容体活性の関与

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概要

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• Serotoninergic (5-HT) neuron is well known as a potent inflammatory mediator which leads to pain behaviour. However, which 5-HT receptor subtypes are involved in peripheral sensitization has not been understood. Sarpogrelate HC1 (MCI) is a newly produced compound and that affects 5-HTergic neurons. No data examined the effect of MCI on inflammatory pain response in relation to activation of selective subtype of 5-HT receptors. The present study was designed to evaluate the modulating effect of systemic or local administration of MCI on the instances of flinching behavior after formalin injection into the rat paw. The effects were compared with those of ketanserine, 5-HT_<2A> antagonist. Male Sprague-Dawley rats were subjected to formalin testing. During 60 min period after injection pain behaviour expressed as flinches of the injected hind paw was counted in 5 min intervals. Rats were divided into two series of study ; 1) i.p. or 2) s.c. drug administration. 1) MCI in a dose of 1, 3, 10mg/kg, given i.p. 30 min prior to formalin injection significantly and dose-dependently attenuated biphasic increases in flinching behavior ; phase 1 (max. 10 flinches/min at 1 min) and phase 2 (max. 17 flinches/min at 35-50 min). The ED50 calculated is 3.5mg/kg for the phase 1 and 3.5mg/kg for the phase 2, respectively. This attenuating effect was reversed by the coadministration of α-methyl-5-HT, 5mg/kg, i.p., 5-HT_<2A> agonist. Ketanserine 10mg/kg, i.p., 5-HT_<2A> antagonist similary attenuated flinches during both phase 1 and 2 periods. 2) MCI in a dose of 5μg given s.c. attenuated biphasic increases in flinching behavior and this effect was attenuated by giving α-methyl-5-HT, 5μg while it did not affect by giving 8-OH-DPAT 5μg, s.c., 5-HT_<1A> agonist. Ketanserine 5μg given s.c., attenuated flinches during both phase 1 and 2 periods. Although the formalin test reflects, as does any acute injury state, a surprisingly complex series of events, the initial afferent barrage generates an augmented state of spinal processing, as well as a subsequent phase in which the ongoing afferent input evokes peripheral tissue inflammation. The present results demonstrate that systemic or local MCI administration provokes antinociceptive effect on formalin-produced inflammatory pain behaiour and this effect was reversed by 5-HT_<2A> receptor agonist. The results confirm that Ketanserin, 5-HT_<2A> receptor antagonist, also attenuated formalin-evoked pain behaviour. It is suggested that MCI has a beneficial effect on developing inflammatory pain behaviour via inhibiting selective 5-HT_<2A> receptor.

• 1999-02-25

著者

• 木庭 浩高

  九州歯科大学歯科麻酔学講座

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