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Centrally mediated antihyperalgesic and antiallodynic effects of zonisamide following partial nerve injury in the mouse.
Naunyn Schmiedebergs Arch Pharmacol. 2005 Aug; 372(2):107-14.NS

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+Show Affiliations

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.jpNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

16217643

Citation

Tanabe, Mitsuo, et al. "Centrally Mediated Antihyperalgesic and Antiallodynic Effects of Zonisamide Following Partial Nerve Injury in the Mouse." Naunyn-Schmiedeberg's Archives of Pharmacology, vol. 372, no. 2, 2005, pp. 107-14.
Tanabe M, Sakaue A, Takasu K, et al. Centrally mediated antihyperalgesic and antiallodynic effects of zonisamide following partial nerve injury in the mouse. Naunyn Schmiedebergs Arch Pharmacol. 2005;372(2):107-14.
Tanabe, M., Sakaue, A., Takasu, K., Honda, M., & Ono, H. (2005). Centrally mediated antihyperalgesic and antiallodynic effects of zonisamide following partial nerve injury in the mouse. Naunyn-Schmiedeberg's Archives of Pharmacology, 372(2), 107-14.
Tanabe M, et al. Centrally Mediated Antihyperalgesic and Antiallodynic Effects of Zonisamide Following Partial Nerve Injury in the Mouse. Naunyn Schmiedebergs Arch Pharmacol. 2005;372(2):107-14. PubMed PMID: 16217643.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Centrally mediated antihyperalgesic and antiallodynic effects of zonisamide following partial nerve injury in the mouse. AU - Tanabe,Mitsuo, AU - Sakaue,Akiko, AU - Takasu,Keiko, AU - Honda,Motoko, AU - Ono,Hideki, Y1 - 2005/10/22/ PY - 2005/03/09/received PY - 2005/08/22/accepted PY - 2005/10/12/pubmed PY - 2006/1/26/medline PY - 2005/10/12/entrez SP - 107 EP - 14 JF - Naunyn-Schmiedeberg's archives of pharmacology JO - Naunyn Schmiedebergs Arch Pharmacol VL - 372 IS - 2 N2 - 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. SN - 0028-1298 UR - https://www.unboundmedicine.com/medline/citation/16217643/Centrally_mediated_antihyperalgesic_and_antiallodynic_effects_of_zonisamide_following_partial_nerve_injury_in_the_mouse_ L2 - https://dx.doi.org/10.1007/s00210-005-0006-5 DB - PRIME DP - Unbound Medicine ER -