Centrally mediated antihyperalgesic and antiallodynic effects of zonisamide following partial nerve injury in the mouse

被引:21
作者
Tanabe, M [1 ]
Sakaue, A [1 ]
Takasu, K [1 ]
Honda, M [1 ]
Ono, H [1 ]
机构
[1] Nagoya City Univ, Grad Sch Pharmaceut Sci, Lab CNS Pharmacol, Mizuho Ku, Nagoya, Aichi 4678603, Japan
关键词
zonisamide; antiepileptic drugs; thermal hyperalgesia; allodynia; neuropathic pain; nitric oxide;
D O I
10.1007/s00210-005-0006-5
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
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 mu g) or intrathecally (i.t., 10 and 30 mu g). 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 mu g, 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.
引用
收藏
页码:107 / 114
页数:8
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