炎症性疼痛時における 5-HT_<2A> 受容体阻害薬の脊髄グルタメートへの影響
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概要
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Serotoninergic neuron located at peripheral sites is thought to be concerned as an one of the pivotal factor of the tissue inflammation which leads to pain behavior. However, which serotonin (5-HT) receptor subtypes is involved in peripheral sensitization is not understood. Sarpogrelate HCl (MCI) is a novel compound which may modulate inflammatory reaction through 5-HT_<2A> receptor antagonism. No data have still been examined the effect of MCI on inflammatory pain response in relation to spinal glutamate (CSF-Glu) release and that whether this effect is affected to 5-HT_<2A> receptor or not. The present study was designed to evaluate the modulating effect of local administration of MCI on the instances of flinching behavior and CSF-Glu after 5-HT injection into the rat paw. Three days after intrathecal implantation of loop-type microdialysis probe in male Sprague-Dawley rats, 100μl of 0.12% 5-HT was subcutaneously injected into left hind paw. Thereafter, simultaneous determinations of microdialysis at 10min. -intervals for glutamate by HPLC-ECD and observation of flinches were performed for 30 min after subcutaneous administration of either drugs (saline for control, MCI, MCI+α-methyl-5-HT) Flinching behavior after injection of 5-HT in saline groupe were observed (max. 22 flinches/min. at 1-2 min). CSF-glu in saline groupe increased by 124% during the first 10 min. MCI in a dose of 5μg given s. c. attenuated both flinching / min and CSF-glu. But those effects were antagonized by giving a-methyl-5-HT, 5μg. Based on the present study, MCI admistration provokes antinociceptive effect on 5-HT-produced inflammatory pain behaviour in relation to CSF-Glu. These effects were reversed by 5-HT_<2A> receptor agonist, suggesting MCI has a beneficial effect on hyperalgesia via inhibiting selective 5-HT_<2A> receptor and CSF-Glu release.
- 九州歯科学会の論文
- 2000-04-25