Chaplan S R, Bach F W, Shafer S L, Yaksh T L
Anesthesiology Research Laboratory, University of California, San Diego, La Jolla 92093-0818, USA.
Anesthesiology. 1995 Oct;83(4):775-85. doi: 10.1097/00000542-199510000-00017.
Lidocaine may be useful in the treatment of neuropathic pain states. The authors hypothesized that lidocaine would reduce tactile allodynia observed in a rat nerve injury model. In an effort to determine the site of drug action, effects after intravenous, intrathecal, and regional administration were compared.
Rats underwent ligation of the left fifth and sixth lumbar spinal nerves. The 50% thresholds (g) for left hind paw withdrawal of awake rats to von Frey hairs were documented before, during, and after intravenous administration of lidocaine at programmed/documented pseudo-steady-state plasma concentrations, and correlated with measured plasma concentrations. Responses to lidocaine application intrathecally and regionally to the injured nerves were also recorded.
In rats with tactile allodynia, intravenous lidocaine yielded 66 +/- 11% of the maximal possible effect on thresholds (100% = normal threshold), versus -1.3 +/- 2.7% for saline infusion. Twenty-one days after lidocaine infusion, 30-40% of the maximal possible effect persisted. Threshold increases depended on plasma concentration, rather than quantity of drug administered: rats receiving 15 mg/kg with higher plasma concentrations (1.2 +/- 0.1 micrograms/ml) showed significant allodynia suppression throughout 7 days of follow-up, whereas rats receiving 15 mg/kg at a slower rate with lower plasma concentrations (0.6 +/- 0.1 microgram/ml) did not. The EC50 for acute allodynia suppression was 0.75 microgram/ml. No such allodynia suppression was seen after intrathecal or regional administration of lidocaine despite transient neural blockade.
Intravenous, but not intrathecal or regionally applied, lidocaine produces dose-dependent suppression of allodynia associated with nerve injury. The effects far outlast plasma concentrations of lidocaine. The mechanism of these prolonged effects is unknown.
利多卡因可能对神经性疼痛状态的治疗有用。作者推测利多卡因会减轻在大鼠神经损伤模型中观察到的触觉异常性疼痛。为了确定药物作用部位，比较了静脉内、鞘内和局部给药后的效果。
对大鼠进行左第五和第六腰脊髓神经结扎。在按程序/记录的伪稳态血浆浓度静脉注射利多卡因之前、期间和之后，记录清醒大鼠左后爪对von Frey毛发的50%阈值（克），并与测得的血浆浓度相关。还记录了鞘内和局部应用利多卡因对受损神经的反应。
在有触觉异常性疼痛的大鼠中，静脉注射利多卡因对阈值产生了最大可能效应的66±11%（100%=正常阈值），而输注生理盐水时为-1.3±2.7%。利多卡因输注21天后，最大可能效应的30 - 40%持续存在。阈值升高取决于血浆浓度，而不是给药量：接受15mg/kg且血浆浓度较高（1.2±0.1微克/毫升）的大鼠在7天的随访中显示出明显的异常性疼痛抑制，而以较慢速度接受15mg/kg且血浆浓度较低（0.6±0.1微克/毫升）的大鼠则没有。急性异常性疼痛抑制的半数有效浓度（EC50）为0.75微克/毫升。尽管有短暂的神经阻滞，但鞘内或局部应用利多卡因后未观察到这种异常性疼痛抑制。
静脉注射而非鞘内或局部应用的利多卡因可产生与神经损伤相关的异常性疼痛的剂量依赖性抑制。这些效应远远超过利多卡因的血浆浓度持续时间。这些延长效应的机制尚不清楚。
