L-bupivacaine Inhibition of Nociceptive Transmission in Rat Peripheral and Dorsal Horn Neurons
L-bupivacaine Inhibition of Nociceptive Transmission in Rat Peripheral and Dorsal Horn Neurons
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DOI：
10.1097/aln.0000000000003596
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发表时间：
2021-01-01
期刊：
影响因子：
8.8
通讯作者：
Yoshimura, Megumu
中科院分区：
文献类型：
--
作者：
Uta, Daisuke;Koga, Kohei;Yoshimura, Megumu
背景：虽然广泛使用的局部麻醉药的单一L-对映体对心血管和中枢神经系统的毒性较小，但其介导的抗伤害作用的机制尚不清楚。作者推测，显着差异的离子通道阻滞能力的对映体的布比卡因将被identified.Methods：作者进行电生理分析，大鼠背根神经节神经元在体外和脊髓transmissioninvivo.Results：在背根神经节，这些麻醉剂降低动作电位的幅度。D-对映体D-布比卡因的半最大抑制浓度几乎相等的A β（29.5 μ M），A δ（29.7 μ M），和C（29.8 μ M）神经元。然而，L-布比卡因的半最大抑制浓度为A δ（19.35 μ M）和C（19.5 μ M）神经元比A β（79.4 μ M）神经元低。此外，D-布比卡因几乎同等地抑制河豚毒素抗性钠电流（平均值+/- SD：对照组的15.8 +/- 10.9%，n = 14，P < 0.001）和河豚毒素敏感性钠电流（对照组的15.4 +/- 15.6%，n = 11，P = 0.004）。相比之下，L-布比卡因抑制河豚毒素抗性钠电流（对照组的26.1 ± 19.5%，n = 18，P < 0.001），但不抑制河豚毒素敏感性钠电流（对照组的74.5 ± 18.2%，n = 11，P = 0.477）。在脊髓背角，L-布比卡因减少了捏诱发的兴奋性突触后电流的面积（对照组的39.4 +/- 11.3%，n = 7，P < 0.001），但没有触摸诱发的反应（对照组的84.2 +/- 14.5%，n = 6，P = 0.826）。相比之下，D-布比卡因同样降低捏和触摸诱发的反应，（分别为对照组的38.8 ± 9.5%，n = 6，P = 0.001，对照组的42.9 ± 11.8%，n = 6，P = 0.013）。这些结果表明布比卡因的L-对映体（L-布比卡因）通过阻断通过C和A δ传入纤维的动作电位传导，有效地抑制伤害性传递到脊髓背角。
Background:Although the widely used single L-enantiomers of local anesthetics have less toxic effects on the cardiovascular and central nervous systems, the mechanisms mediating their antinociceptive actions are not well understood. The authors hypothesized that significant differences in the ion channel blocking abilities of the enantiomers of bupivacaine would be identified.Methods:The authors performed electrophysiologic analysis on rat dorsal root ganglion neurons in vitro and on spinal transmissions in vivo.Results:In the dorsal root ganglion, these anesthetics decreased the amplitudes of action potentials. The half-maximum inhibitory concentrations of D-enantiomer D-bupivacaine were almost equal for A beta (29.5 mu M), A delta (29.7 mu M), and C (29.8 mu M) neurons. However, the half-maximum inhibitory concentrations of L-bupivacaine was lower for A delta (19.35 mu M) and C (19.5 mu M) neurons than for A beta (79.4 mu M) neurons. Moreover, D-bupivacaine almost equally inhibited tetrodotoxin-resistant (mean +/- SD: 15.8 +/- 10.9% of the control, n = 14, P < 0.001) and tetrodotoxin-sensitive (15.4 +/- 15.6% of the control, n = 11, P = 0.004) sodium currents. In contrast, L-bupivacaine suppressed tetrodotoxin-resistant sodium currents (26.1 +/- 19.5% of the control, n = 18, P < 0.001) but not tetrodotoxin-sensitive sodium currents (74.5 +/- 18.2% of the control, n = 11, P = 0.477). In the spinal dorsal horn, L-bupivacaine decreased the area of pinch-evoked excitatory postsynaptic currents (39.4 +/- 11.3% of the control, n = 7, P < 0.001) but not touch-evoked responses (84.2 +/- 14.5% of the control, n = 6, P = 0.826). In contrast, D-bupivacaine equally decreased pinch- and touch-evoked responses (38.8 +/- 9.5% of the control, n = 6, P = 0.001, 42.9 +/- 11.8% of the control, n = 6, P = 0.013, respectively).Conclusions:These results suggest that the L-enantiomer of bupivacaine (L-bupivacaine) effectively inhibits noxious transmission to the spinal dorsal horn by blocking action potential conduction through C and A delta afferent fibers.