Chapman V, Wildman M A, Dickenson A H
Department of Pharmacology, University College London, UK. v.chapman. @ucl.ac.uk
Pain. 1997 Jul;71(3):285-95. doi: 10.1016/s0304-3959(97)03365-4.
A selective blockade of the relay of messages by C-fibres into the spinal cord is a logical approach to the reduction of nociceptive transmission. Here we compared the effect of two distinctly different sodium channel blockers, the local anaesthetic bupivacaine and the novel anti-epileptic lamotrigine, on the responses of dorsal horn neurones following noxious and innocuous stimulation. Dorsal horn neuronal responses following acute repetitive C-fibre electrical stimulation (three times the C-fibre threshold at 0.5 Hz) were recorded in intact halothane anaesthetised rats. Wind up, an enhanced C-fibre evoked response of dorsal horn neurones, and an associated post discharge were observed following repetitive stimulation. The effects of spinally administered bupivacaine and lamotrigine on the dorsal horn neuronal responses were investigated. Spinal bupivacaine (25-1000 microg/50 microl) dose dependently reduced the C-fibre evoked responses (r2 = 0.5, P < 0.0003), wind up (r2 = 0.4, P < 0.002) and the post discharge (r2 = 0.34, P < 0.005) of these neurones. The effects of bupivacaine were long lasting, up to 120 min post-administration. The Abeta-fibre evoked responses were not dose-dependently reduced by bupivacaine. Spinal lamotrigine (50-1000 microg/50 microl) did not significantly reduce the C- or Abeta-fibre evoked responses. In contrast there was a tendency for wind up and post discharge to be facilitated by lamotrigine. Although both bupivacaine and lamotrigine are sodium channel blockers, the effects of the two drugs on the C-fibre and Abeta-fibre evoked responses were completely different. Bupivacaine reduced C-fibre evoked responses whereas lamotrigine had a tendency to facilitate responses. The profile of sodium channel blockers would appear highly diverse and the status of lamotrigine as a potential analgesic remains unclear.
选择性阻断C类纤维向脊髓传递信息是减少伤害性感受传递的合理方法。在此，我们比较了两种截然不同的钠通道阻滞剂——局部麻醉药布比卡因和新型抗癫痫药拉莫三嗪——对伤害性和无害性刺激后背角神经元反应的影响。在完整的氟烷麻醉大鼠中记录急性重复C类纤维电刺激（0.5 Hz时为C类纤维阈值的三倍）后背角神经元的反应。在重复刺激后观察到了“wind up”现象，即背角神经元C类纤维诱发反应增强以及相关的后放电。研究了脊髓给予布比卡因和拉莫三嗪对背角神经元反应的影响。脊髓注射布比卡因（25 - 1000微克/50微升）剂量依赖性地降低了这些神经元的C类纤维诱发反应（r2 = 0.5，P < 0.0003）、“wind up”现象（r2 = 0.4，P < 0.002）和后放电（r2 = 0.34，P < 0.005）。布比卡因的作用持续时间长，给药后长达120分钟。布比卡因并未剂量依赖性地降低Aβ纤维诱发反应。脊髓注射拉莫三嗪（50 - 1000微克/50微升）并未显著降低C类或Aβ纤维诱发反应。相反，拉莫三嗪有促进“wind up”现象和后放电的趋势。虽然布比卡因和拉莫三嗪都是钠通道阻滞剂，但两种药物对C类纤维和Aβ纤维诱发反应的影响完全不同。布比卡因降低C类纤维诱发反应，而拉莫三嗪有促进反应的趋势。钠通道阻滞剂的情况似乎高度多样，拉莫三嗪作为潜在镇痛药的地位仍不明确。
