The effects of QO-58 on Na+ currents in DRG neurons and pain behavior of adult rats
作者单位：Department of PharmacologyHebei Medical University
会议名称：《中国神经科学学会第十届全国学术会议》
会议日期：2013年
学科分类：0710[理学-生物学] 07[理学] 071006[理学-神经生物学]
关 键 词：QO-58 sodium channel patch clamp CCL2 CFA pain model dorsal root ganglion rat
摘 要：Objective QO-58 is a potent opener of Kv7 *** study found that QO-58 shows anticon-vulsant and analgesic *** epilepsy and pain are closely related to abnormal activity of sodium channel in sensory *** study is intended to investigate whether QO-58 could also affect Na currents besides its activation of K currents,and whether the pain behavior produced by CCL2(Monocyte chemoattractant protein-1) and CFA(Freund’s complete adjuvant)could be prevented by *** Sodium current was measured by whole cell patch clamp ***2/CFA-induced inflammatory pain model of rats was *** allodynia and thermal hyperalgesia were assessed using the von Frey filaments and radiate heat tests,***(1) QO-58 caused a concentration-dependent inhibition of sodium current in DRG *** the concentration of 10 μM to 30 μ,QO-58 was more effective in reducing TTX-sensitive(TTX-S) than TTX-resistant(TTX-R) Na currents.(2) QO-58 induced a right shift of the voltage-dependent activation curve of total and TTX-S channels,and also produced a leftward shift of the voltage-dependent inactivation curve of total,TTX-R,NaV1.8 and TTX-S Na *** with the fast inactivation,QO-58 shifted the slow-inactivation channel curve to more hyperpolarized direction.(3) Application of QO-58(30 mg/kg,i.p.) increased the withdrawal latency to thermal stimulus of CCL2/CFA-induced rats,which was not affected by Kv7 specific inhibitor *** QO-58 significantly increased the threshold for the pain behavior induced by thermal stimulation of CCL2/CFA rats pain *** analgesic effect of QO-58 mentioned above is possibly not related to the opening of Kv7 K channels but rather related to the blockade of voltage-gated sodium channels.