右美托咪啶通过抑制超极化激活内向电流减轻机械性触诱发痛

Dexmedetomidine suppresses mechanical allodynia by inhibiting hyperpolarizationactivated inward current

本文旨在研究右美托咪啶(dexmedetomidine,DEX)对慢性压迫背根神经节(chronic compression of dorsal root ganglion,CCD)引起的机械性触诱发痛的作用及机制。制备Sprague Dawley(SD)大鼠CCD模型,用痛行为学方法检测机械性触诱发痛,用全细胞膜片钳技术检测背根神经节(dorsal root ganglion,DRG)C类和A_δ类神经元兴奋性和超极化激活内向电流(hyperpolarization-activated inward currents,I_h)的变化。结果显示:鞘内注射DEX显著减轻CCD大鼠机械性触诱发痛(P<0.05);在CCD大鼠DRG C类和A_δ类神经元上,DEX显著提高细胞基强度和后超极化电位,降低I_h电流密度。上述结果提示,DEX可能通过抑制C类和A_δ类DRG神经元I_h电流,降低神经元兴奋性,从而减轻神经病理性疼痛。

The purpose of the present study was to investigate the effects of dexmedetomidine（DEX） on neuropathic pain in the chronic compression of dorsal root ganglion（CCD） rat model and the underlying mechanism. Pain behavioral tests were applied to observe the effects of DEX on mechanical allodynia in Sprague Dawley（SD） rats. Whole cell patch clamp was used to observe the influence of DEX on excitability and hyperpolarization-activated inward current（I_h） of C-and A_δ-type dorsal root ganglion（DRG） neurons. The results showed that mechanical allodynia of CCD rats was significantly inhibited by DEX（P 〈 0.05）. In C-and A_δ-type DRG neurons from the CCD rats, DEX significantly increased rheobase and after hyperpolarizing potential, as well as decreased I_hcurrent density. These results suggest that DEX could attenuate the neuropathic pain in the CCD rats, and the mechanism might be related to the depressed I_h current density and excitability of C-and A_δ-type DRG neurons.