Department of Anesthesiology Mannheim, Medical Faculty Mannheim, Heidelberg University, Germany.
Eur J Pain. 2012 Apr;16(4):543-9. doi: 10.1016/j.ejpain.2011.08.004.
We investigated the effects of a non-specific sodium channel blocker (lidocaine) on heat pain thresholds and mechanical impact pain at day 7 and 21 after intradermal injection of 1 μg NGF. Measurements were performed in 12 healthy male subjects prior to and 5 min after intradermal injection of 150 μl lidocaine administered at concentrations of 0.01% (∼0.4 mM) and 0.1% (∼4 mM) to both NGF and control skin sites. NGF caused a maximum reduction of heat pain thresholds at day 7 (NGF 42.6 ± 0.6 vs. 49.4 ± 0.3 °C in control skin). Lidocaine sensitized normal skin for heat pain, but reduced heat hyperalgesia after NGF at day 7 (44.3 ± 0.8 °C, lidocaine 0.1%; p < 0.005). Pain upon supra-threshold mechanical impact stimulation was increased after NGF at day 7 (VAS 29 + 5) and massively enhanced at day 21 (VAS 64 + 5, p < 0.001). Lidocaine dose-dependently attenuated mechanically-induced pain at both control and NGF-treated sites. Maximum lidocaine effects on mechanical hyperalgesia were recorded at day 21 in NGF skin (pain reduction to VAS 37 ± 4, p < 0.00001). Repetitive impact stimuli caused increasingly more pain at the NGF sites at day 21 and this pain increase was efficiently suppressed by lidocaine 0.1%. Lidocaine differentially affects NGF-induced mechanical hyperalgesia (analgesic effect) and heat sensitivity of nociceptors (sensitizing effect). These opposing responses may be attributed to block of sodium channels vs. sensitization of TRPV1. NGF-evoked extreme mechanical impact pain indicates high action potential discharge frequencies, which might be more susceptible to lidocaine block.
我们研究了一种非特异性钠离子通道阻滞剂（利多卡因）对皮内注射 1μg NGF 后第 7 天和第 21 天热痛阈值和机械冲击痛的影响。在皮内注射 150μl 利多卡因之前和之后，我们对 12 名健康男性受试者进行了测量，利多卡因的浓度分别为 0.01%（约 0.4mM）和 0.1%（约 4mM），用于 NGF 和对照皮肤部位。NGF 在第 7 天引起最大的热痛阈值降低（NGF 为 42.6±0.6°C，对照皮肤为 49.4±0.3°C）。利多卡因使正常皮肤对热痛敏感，但在第 7 天减少了 NGF 后的热痛觉过敏（44.3±0.8°C，利多卡因 0.1%；p<0.005）。在第 7 天，机械性超阈值刺激引起的疼痛增加（VAS 29+5），并在第 21 天大大增强（VAS 64+5，p<0.001）。利多卡因剂量依赖性地减轻了对照和 NGF 处理部位的机械性疼痛。在 NGF 皮肤中，最大的利多卡因对机械性痛觉过敏的作用在第 21 天记录（疼痛减轻至 VAS 37±4，p<0.00001）。在第 21 天，NGF 部位的重复冲击刺激引起的疼痛越来越多，利多卡因 0.1%有效地抑制了这种疼痛增加。利多卡因对 NGF 诱导的机械性痛觉过敏（镇痛作用）和伤害感受器的热敏感性（敏化作用）有不同的影响。这些相反的反应可能归因于钠离子通道的阻断与 TRPV1 的敏化。NGF 诱发的极度机械性冲击痛表明动作电位放电频率较高，可能更容易受到利多卡因的阻断。
