title: Centrally mediated antihyperalgesic and antiallodynic effects of zonisamide following partial nerve injury in the mouse.
abstract: 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.
authors.affiliation: Laboratory of CNS Pharmacology, Graduate School of Pharmaceutical Sciences, Nagoya City University, 3-1 Tanabe-dori, Mizuho-ku, Nagoya, 467-8603, Japan. mitana@phar.nagoya-cu.ac.jp
authors.forename: Mitsuo
authors.initials: M
authors.lastname: Tanabe
authors.forename: Akiko
authors.initials: A
authors.lastname: Sakaue
authors.forename: Keiko
authors.initials: K
authors.lastname: Takasu
authors.forename: Motoko
authors.initials: M
authors.lastname: Honda
authors.forename: Hideki
authors.initials: H
authors.lastname: Ono
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage / Q000627:therapeutic use*; D002490:Central Nervous System / Q000187:drug effects / Q000201:enzymology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D006358:Hot Temperature; D006930:Hyperalgesia / Q000188:drug therapy* / Q000209:etiology; D007276:Injections, Intraventricular; D007278:Injections, Spinal; D007555:Isoxazoles / Q000008:administration & dosage / Q000627:therapeutic use*; D008297:Male; D051379:Mice; D019331:NG-Nitroarginine Methyl Ester / Q000008:administration & dosage; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D010146:Pain / Q000188:drug therapy* / Q000209:etiology; D017288:Pain Threshold / Q000187:drug effects; D012584:Sciatic Nerve / Q000601:surgery; D013997:Time Factors; D014110:Touch; D000078305:Zonisamide
chemical_list: D000975:Antioxidants; D007555:Isoxazoles; D000078305:Zonisamide; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester