Lee Tsung-Hsing, Wang Ching-Jen, Wu Ping-Ching, Buerkle Hartmut, Lin S-H, Yang Lin-Cheng
Anesthesiology Research Laboratory, Department of Anesthesiology, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University, 123 Ta-Pei Road, Niao Shung Hsiang, Hsien, 833, Kaohsiung, Taiwan.
Life Sci. 2002 May 10;70(25):3039-47. doi: 10.1016/s0024-3205(02)01546-1.
Intrathecal (IT) lamotrigine, a sodium channel blocker which suppresses neuronal release of glutamate, has been shown to produce a long-lasting antihyperalgesic effect in the neuropathic pain models. In the present study, we examined the anti-hyperalgesic effects of pre- versus post-treatment of IT lamotrigine in an animal inflammatory pain model, the inflamed knee joint model of the rat. Thermal and mechanical antinociception was assessed in rats using a modified Hargreaves box and von Frey hairs. Induction of tonic persistent inflammatory pain was induced by intra-articular injection (i.a.) of a carrageenan-kaolin mixture (CK) into the right knee-joint. Rats were randomly assigned to the groups receiving IT lamotrigine in distinct doses of 5, 50 or 100 ug either pre- (10 min before CK injection) or post-inflammation induction (4 h or 23 h). We observed that CK injection resulted in a significant thermal and mechanical hyperalgesia throughout a 24-h observation period. Pre-treatment with IT lamotrigine revealed a time and dose-dependent suppression of thermal and mechanical hyperalgesia, whereas the post-treatment with IT lamotrigine only showed an effect for mechanical nociception.
IT Lamotrigine is antihyperalgesic at a dose larger than 50 ug in the early phase of inflammatory pain model. It reverses tactile allodynia but not thermal hyperalgesia when given after the inflammation induction.
鞘内注射拉莫三嗪是一种钠通道阻滞剂，可抑制谷氨酸的神经元释放，已证实在神经病理性疼痛模型中可产生持久的抗痛觉过敏作用。在本研究中，我们在动物炎性疼痛模型（大鼠膝关节炎症模型）中研究了鞘内注射拉莫三嗪预处理与后处理的抗痛觉过敏作用。使用改良的哈格里夫斯箱和von Frey毛发评估大鼠的热和机械性抗伤害感受。通过将角叉菜胶-高岭土混合物（CK）关节内注射（i.a.）到右膝关节来诱导强直性持续性炎性疼痛。将大鼠随机分为在不同剂量5、50或100μg下接受鞘内注射拉莫三嗪的组，分别在预处理（CK注射前10分钟）或炎症诱导后（4小时或23小时）。我们观察到，CK注射在整个24小时观察期内导致显著的热和机械性痛觉过敏。鞘内注射拉莫三嗪预处理显示出对热和机械性痛觉过敏的时间和剂量依赖性抑制，而鞘内注射拉莫三嗪后处理仅对机械性伤害感受有作用。
在炎性疼痛模型的早期阶段，鞘内注射拉莫三嗪剂量大于50μg时具有抗痛觉过敏作用。炎症诱导后给予时，它可逆转触觉异常性疼痛，但不能逆转热痛觉过敏。
