Woolf Clifford J, Wiesenfeld-Hallin Zsuzsanna
Cerebral Functions Research Group, Department of Anatomy, University College London, Gower Street, London WC1E 6BT U.K. Department of Clinical Neurophysiology, Huddinge University Hospital, S141 86 HuddingeSweden.
Pain. 1985 Dec;23(4):361-374. doi: 10.1016/0304-3959(85)90006-5.
An electrophysiological analysis of the antinociceptive effects of systemic lidocaine and its longer acting primary amine congener, tocainide, has been performed in the decerebrate-spinal unanaesthetised rat. Neither of these local anaesthetic drugs when administered systemically in doses of up to 10 mg/kg (lidocaine) or 100 mg/kg (tocainide), produced any evidence of a block in the conduction of action potentials in A beta, A delta or C primary afferents. The local anaesthetics also failed to reduce mustard oil induced neurogenic extravasation, a test of cutaneous C-fibre terminal function. Lidocaine produced a transient (1-2 min) depression in monosynaptic reflexes at doses of greater than or equal to 1 mg/kg while tocainide had no effect on this reflex at any dose up to a 100 mg/kg. Both drugs, however, significantly suppressed the C-fibre evoked polysynaptic reflex generated by stimulating the sural nerve. The tocainide effect was longer lasting with less action on the short latency A beta-evoked reflex than lidocaine. The reflex activity in hamstring flexor alpha-motoneurones evoked by pinching the toes of the ipsilateral hind paw was reduced by both drugs but not abolished. Thermal and noxious chemical evoked reflexes were, however, completely suppressed by the local anaesthetic drugs, again with a longer action from tocainide. These results demonstrate that the systemic administration of drugs which increase the inactivation of sodium channels can produce a selective central block of certain types of afferent evoked activity in the spinal cord. There are resemblances between the selective C-fibre suppressing actions of systemically administered local anaesthetic and the pharmacological actions of narcotic opiates which may represent a similar mechanism for the analgesic action of these quite different classes of drugs.
在去大脑脊髓未麻醉大鼠中，对全身应用利多卡因及其长效伯胺同类物妥卡尼的抗伤害感受作用进行了电生理分析。当以高达10mg/kg（利多卡因）或100mg/kg（妥卡尼）的剂量全身给药时，这两种局部麻醉药均未显示出对Aβ、Aδ或C初级传入纤维动作电位传导产生阻滞的任何迹象。局部麻醉药也未能减少芥子油诱导的神经源性血管外渗，这是一种皮肤C纤维终末功能的测试。利多卡因在剂量大于或等于1mg/kg时会使单突触反射产生短暂（1 - 2分钟）的抑制，而妥卡尼在高达100mg/kg的任何剂量下对该反射均无影响。然而，两种药物均显著抑制了刺激腓肠神经所产生的C纤维诱发的多突触反射。与利多卡因相比，妥卡尼的作用持续时间更长，对短潜伏期Aβ诱发反射的作用更小。捏同侧后爪脚趾所诱发的腘绳肌屈肌α运动神经元的反射活动在两种药物作用下均降低但未被消除。然而，热刺激和有害化学刺激诱发的反射被局部麻醉药完全抑制，同样妥卡尼的作用持续时间更长。这些结果表明，全身应用增加钠通道失活的药物可在脊髓中对某些类型的传入诱发活动产生选择性中枢阻滞。全身应用局部麻醉药的选择性C纤维抑制作用与麻醉性阿片类药物的药理作用之间存在相似之处，这可能代表了这些截然不同类别的药物镇痛作用的类似机制。
