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  • Zonisamide: Antihyperalgesic efficacy, the role of serotonergic receptors on efficacy in a rat model for painful diabetic neuropathy.

Zonisamide: Antihyperalgesic efficacy, the role of serotonergic receptors on efficacy in a rat model for painful diabetic neuropathy.

Life sciences (2013-12-24)
Nurcan Bektas, Rana Arslan, Yusuf Ozturk
ABSTRACT

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. 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. 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. 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.

MATERIALS
Product Number
Brand
Product Description

Supelco
Carbamazepine solution, 1.0 mg/mL in methanol, ampule of 1 mL, certified reference material, Cerilliant®
Supelco
Morphine sulfate salt solution, 1.0 mg/mL in methanol, drug standard
Sigma-Aldrich
Streptozocin, ≥75% α-anomer basis, ≥98% (HPLC), powder
Sigma-Aldrich
Morphine sulfate salt pentahydrate
Sigma-Aldrich
Zonisamide sodium salt, ≥98% (HPLC), powder
Supelco
Carbamazepine, Pharmaceutical Secondary Standard; Certified Reference Material
Sigma-Aldrich
Carbamazepine, meets USP testing specifications
Sigma-Aldrich
Carbamazepine, powder
Supelco
Zonisamide solution, 1.0 mg/mL in methanol, ampule of 1 mL, certified reference material, Cerilliant®
Supelco
Morphine solution, 1.0 mg/mL in methanol, ampule of 1 mL, certified reference material, Cerilliant®
Supelco
Morphine solution, 100 μg/mL in methanol, ampule of 1 mL, certified reference material, Cerilliant®