The effects of QO-58 on Na~+ currents in DRG neurons and pain behavior of adult rats
【摘要】：Objective QO-58 is a potent opener of Kv7 channels.Previous study found that QO-58 shows anticon-vulsant and analgesic effects.Both epilepsy and pain are closely related to abnormal activity of sodium channel in sensory system.This 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 QO-58.Methods Sodium current was measured by whole cell patch clamp technique.CCL2/CFA-induced inflammatory pain model of rats was established.Mechanical allodynia and thermal hyperalgesia were assessed using the von Frey filaments and radiate heat tests,respectively.Results(1) QO-58 caused a concentration-dependent inhibition of sodium current in DRG neurons.Within 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~+ currents.Compared 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 XE991.Conclusion QO-58 significantly increased the threshold for the pain behavior induced by thermal stimulation of CCL2/CFA rats pain model.This 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.