title: Zonisamide: Antihyperalgesic efficacy, the role of serotonergic receptors on efficacy in a rat model for painful diabetic neuropathy.
abstract: OBJECTIVE
  The purpose of this study was to compare the changes of antihyperalgesic effectiveness of zonisamide (25 and 50 mg/kg), an antiepileptic drug, on the early and late phases of neuropathy and to investigate the role of serotonergic descending inhibitory pain pathways in antihyperalgesic effectiveness of zonisamide in the streptozotocin-induced rat model for painful diabetic neuropathy.
  
  
  METHODS
  The hot-plate and tail-immersion, to determine thermal thresholds, and paw pressure withdrawal tests, to determine mechanical thresholds, were performed as hyperalgesia tests. To investigate the role of serotonergic pathway, 1 mg/kg ketanserin (5-HT(2A/2C) antagonist) and ondansetron (serotonin 5-HT₃ receptor antagonist) were used.
  
  
  RESULTS
  Zonisamide enhanced pain thresholds significantly in the 3rd, 6th and 8th weeks as the reference drugs morphine (5 mg/kg) and carbamazepine (32 mg/kg, tested only in the 3rd week). There were no observed differences on the potency of antihyperalgesic effect between weeks and between doses. Each antagonist reversed the effect of zonisamide in the hot-plate and tail-immersion tests significantly, but, relatively in the paw pressure withdrawal tests.
  
  
  CONCLUSIONS
  These results support the role for zonisamide in the management of diabetic neuropathic pain in all phases. Serotonin 5-HT2A/2C and 5-HT₃ receptors are involved in the antihyperalgesic effect of zonisamide by enhancement of thermal threshold, and partially by mechanical threshold, so they may not mediate mechanical hyperalgesia in diabetic neuropathy.
authors.affiliation: Anadolu University, Faculty of Pharmacy, Department of Pharmacology, 26470 Eskisehir, Turkey. Electronic address: nurcanbektas@anadolu.edu.tr.
authors.forename: Nurcan
authors.initials: N
authors.lastname: Bektas
authors.affiliation: Anadolu University, Faculty of Pharmacy, Department of Pharmacology, 26470 Eskisehir, Turkey.
authors.forename: Rana
authors.initials: R
authors.lastname: Arslan
authors.affiliation: Anadolu University, Faculty of Pharmacy, Department of Pharmacology, 26470 Eskisehir, Turkey.
authors.forename: Yusuf
authors.initials: Y
authors.lastname: Ozturk
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000008:administration & dosage / Q000494:pharmacology*; D002220:Carbamazepine / Q000494:pharmacology; D003929:Diabetic Neuropathies / Q000188:drug therapy*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005260:Female; D006930:Hyperalgesia / Q000188:drug therapy*; D007555:Isoxazoles / Q000008:administration & dosage / Q000494:pharmacology*; D007650:Ketanserin / Q000494:pharmacology; D008297:Male; D009020:Morphine / Q000494:pharmacology; D017294:Ondansetron / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D044402:Receptor, Serotonin, 5-HT2A / Q000187:drug effects / Q000378:metabolism; D044405:Receptor, Serotonin, 5-HT2C / Q000187:drug effects / Q000378:metabolism; D044406:Receptors, Serotonin, 5-HT3 / Q000378:metabolism; D013311:Streptozocin; D000078305:Zonisamide
chemical_list: D000927:Anticonvulsants; D007555:Isoxazoles; D044402:Receptor, Serotonin, 5-HT2A; D044405:Receptor, Serotonin, 5-HT2C; D044406:Receptors, Serotonin, 5-HT3; D002220:Carbamazepine; D000078305:Zonisamide; D017294:Ondansetron; D013311:Streptozocin; D009020:Morphine; D007650:Ketanserin
keywords: Neuropathic pain; Serotonergic descending pain pathways; Zonisamide