Tanabe Mitsuo, Sakaue Akiko, Takasu Keiko, Honda Motoko, Ono Hideki
Laboratory of CNS Pharmacology, Graduate School of Pharmaceutical Sciences, Nagoya City University, 3-1 Tanabe-dori, Mizuho-ku, Nagoya, 467-8603, Japan.
Naunyn Schmiedebergs Arch Pharmacol. 2005 Aug;372(2):107-14. doi: 10.1007/s00210-005-0006-5. Epub 2005 Oct 22.
Some antiepileptic drugs are used clinically to relieve neuropathic pain. We have evaluated the effects and investigated the possible mechanisms of action of zonisamide, an antiepileptic drug, on thermal hyperalgesia and tactile allodynia in a murine chronic pain model that was prepared by partial ligation of the sciatic nerve. Subcutaneously administered zonisamide (10 and 30 mg/kg) produced antihyperalgesic and antiallodynic effects in a dose-dependent manner; these effects were manifested by elevation of the withdrawal threshold in response to a thermal (plantar test) or mechanical (von Frey) stimulus, respectively. Similar analgesic effects were obtained in both the plantar and von Frey tests when zonisamide was injected either intracerebroventricularly (i.c.v., 10 and 30 microg) or intrathecally (i.t., 10 and 30 microg). It is thought that this elevation of the thermal and mechanical withdrawal thresholds after local injection of zonisamide is not generated secondarily via impaired motor activity, since zonisamide (30 microg, i.c.v. or i.t.) did not affect locomotor activity, as assessed in sciatic-nerve-ligated mice. Moreover, the nitric oxide synthase inhibitor L-NAME, when injected either i.c.v. or i.t., potentiated the analgesic effects of zonisamide. In contrast, neither i.c.v. nor i.t. zonisamide produced antinociceptive effects against acute thermal and mechanical nociception in non-ligated mice. Together, following peripheral nerve injury, it appears that zonisamide produces centrally mediated antihyperalgesic and antiallodynic effects partly via the blockade of nitric oxide synthesis.
一些抗癫痫药物在临床上用于缓解神经性疼痛。我们评估了抗癫痫药物唑尼沙胺对坐骨神经部分结扎制备的小鼠慢性疼痛模型中热痛觉过敏和触觉异常性疼痛的影响，并研究了其可能的作用机制。皮下注射唑尼沙胺（10和30mg/kg）以剂量依赖性方式产生抗痛觉过敏和抗异常性疼痛作用；这些作用分别表现为对热刺激（足底试验）或机械刺激（von Frey试验）的撤药阈值升高。当唑尼沙胺脑室内注射（i.c.v.，10和30μg）或鞘内注射（i.t.，10和30μg）时，在足底试验和von Frey试验中均获得了类似的镇痛效果。据认为，局部注射唑尼沙胺后热和机械撤药阈值的升高不是通过运动活动受损继发产生的，因为唑尼沙胺（30μg，i.c.v.或i.t.）对坐骨神经结扎小鼠的运动活动没有影响。此外，一氧化氮合酶抑制剂L-NAME脑室内或鞘内注射时，增强了唑尼沙胺的镇痛作用。相反，脑室内或鞘内注射唑尼沙胺对未结扎小鼠的急性热和机械伤害性感受均未产生抗伤害性作用。总之，在周围神经损伤后，唑尼沙胺似乎部分通过阻断一氧化氮合成产生中枢介导的抗痛觉过敏和抗异常性疼痛作用。
