Subanesthetic concentrations of lidocaine selectively inhibit a nociceptive response in the isolated rat spinal cord
Subanesthetic concentrations of lidocaine selectively inhibit a nociceptive response in the isolated rat spinal cord
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DOI：
10.1016/0304-3959(94)00117-w
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发表时间：
1995-02
期刊：
影响因子：
7.4
通讯作者：
R. Jaffe;M. A. Rowe
中科院分区：
文献类型：
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作者：
R. Jaffe;M. A. Rowe
已知全身给药的局部麻醉剂可在多种疼痛状态下提供镇痛;然而，作用部位和产生这些作用的机制仍存在疑问。在本研究中，研究了低浓度（神经传导亚阻断）利多卡因对脊髓伤害性电位的影响。从新生大鼠中取出脊髓并保持在体外。将腰后根和同侧前根分别连接到抽吸电极上进行刺激和记录。在对照测量的稳定期（60-120 min）后，将每种制剂暴露于单一浓度的利多卡因（30-60 min），然后返回对照灌注液进行恢复（60-120 min）。将数据数字化，并计算单突触和慢腹根电位（VRP）的积分。低浓度的利多卡因产生了选择性降低的幅度慢-VRP。当利多卡因浓度为1-10 μg/ml（3.6-36 μM）时，慢VRP从对照组的79%降至36%。在无药物灌注液中，恢复至暴露前对照水平缓慢，有时在60-120分钟后无法完全恢复。VRP的单突触成分不受任何浓度的利多卡因的影响，这表明慢VRP的抑制不能归因于简单的传导阻滞。在灌流液中加入0.1 μM纳洛酮对利多卡因诱导的抑郁的影响极小。虽然类似于吗啡的选择性作用，利多卡因的镇痛作用似乎并不主要通过阿片受体介导。河豚毒素（一种选择性钠通道阻滞剂）的亚阻滞浓度不能模拟利多卡因的作用。然而，亚阻断浓度的苯佐那酯（一种口服有效的局部麻醉剂）确实对慢VRP产生了利多卡因样的选择性作用。本研究表明，临床相关浓度的利多卡因可以选择性地抑制离体大鼠脊髓中的伤害性反应。我们认为利多卡因全身镇痛的作用部位至少部分在脊髓水平。
Systemically administered local anesthetics are known to provide analgesia in a variety of pain states; however, the site of action and the mechanism by which these effects are produced remain in question. In the present study, the effects of low (subblocking for nerve conduction) concentrations of lidocaine on a spinal cord nociceptive potential were studied. Spinal cords were removed from neonatal rats and maintained in vitro. Lumbar dorsal and ipsilateral ventral roots were attached to suction electrodes for stimulation and recording, respectively. Following a stabilization period (60–120 min) with control measurements, each preparation was exposed to a single concentration of lidocaine (30–60 min) then returned to control perfusate for recovery (60–120 min). Data were digitized and integrals computed for both monosynaptic and slow ventral root potentials (VRP). Low concentrations of lidocaine produced a selective reduction in the magnitude of the slow-VRP. At lidocaine concentrations of 1–10 μg/ml (3.6–36 μM), the slow-VRP was reduced from 79% to 36% of control. Recovery to pre-exposure control levels was slow and sometimes not complete after 60–120 min in drug-free perfusate. The monosynaptic component of the VRP was unaffected by lidocaine at any concentration, suggesting that the depression of the slow-VRP cannot be attributed to simple conduction block. The addition of naloxone 0.1 μM to the perfusate had minimal effect on lidocaine-induced depression. Although resembling the selective effects of morphine, the antinociceptive effects of lidocaine do not appear to be primarily mediated through opiate receptors. Subblocking concentrations of tetrodotoxin, a selective sodium-channel blocker, did not mimic the effects of lidocaine. However, a subblocking concentration of benzonatate, an orally effective local anesthetic, did produce lidocaine-like selective effects on the slow-VRP. This study demonstrated that lidocaine at clinically relevant concentrations can selectively depress a well-characterized nociceptive response in the isolated rat spinal cord. We propose that the site of action for systemic lidocaine analgesia is, at least in part, at the level of the spinal cord.