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Cilostazol Ameliorates Peripheral Neuropathic Pain in Streptozotocin-Induced Type I Diabetic Rats

Background: Cilostazol is an antiplatelet agent with vasodilating, endothelial function restoration, and anti-inflammatory effects. This study aims to investigate the efficacy of oral cilostazol for preventing the development of diabetic peripheral neuropathy (DPN). Materials and Methods: Ninety adu...

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Autores principales: Cheng, Kuang-I., Wang, Hung-Chen, Tseng, Kuang-Yi, Wang, Yi-Hsuan, Chang, Chung-Yu, Chen, Yi-Jing, Lai, Chung-Sheng, Chen, Dar-Ren, Chang, Lin-Li
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8804339/
https://www.ncbi.nlm.nih.gov/pubmed/35115925
http://dx.doi.org/10.3389/fphar.2021.771271
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author Cheng, Kuang-I.
Wang, Hung-Chen
Tseng, Kuang-Yi
Wang, Yi-Hsuan
Chang, Chung-Yu
Chen, Yi-Jing
Lai, Chung-Sheng
Chen, Dar-Ren
Chang, Lin-Li
author_facet Cheng, Kuang-I.
Wang, Hung-Chen
Tseng, Kuang-Yi
Wang, Yi-Hsuan
Chang, Chung-Yu
Chen, Yi-Jing
Lai, Chung-Sheng
Chen, Dar-Ren
Chang, Lin-Li
author_sort Cheng, Kuang-I.
collection PubMed
description Background: Cilostazol is an antiplatelet agent with vasodilating, endothelial function restoration, and anti-inflammatory effects. This study aims to investigate the efficacy of oral cilostazol for preventing the development of diabetic peripheral neuropathy (DPN). Materials and Methods: Ninety adult male Sprague-Dawley rats were divided into five groups: 1) naïve (control); 2) diabetic (DM); 3) DM receiving 10 mg/kg cilostazol (cilo-10); 4) DM receiving 30 mg/kg cilostazol (cilo-30); and 5) DM receiving 100 mg/kg cilostazol (cilo-100). Hindpaw responses to thermal and mechanical stimuli were measured. Activation of microglia and astrocytes in the spinal dorsal horn (SDH) and expression of NaVs in the dorsal root ganglia (DRG) were examined with Western blots and immunofluorescence. Results: DM rats displayed decreased withdrawal thresholds to mechanical stimuli (mechanical allodynia) and blunted responses to thermal stimuli. In addition, the expression of microglia increased, but astrocytes were reduced in the SDH. Upregulation of Nav −1.1, 1.2, −1.3, −1.6, and −1.7 and downregulation of Nav-1.8 were observed in the DRG. The DM rats receiving cilostazol all returned DM-induced decrease in withdrawal threshold to mechanical stimuli and attenuated neuropathic pain. Additionally, all cilostazol treatments suppressed the level of activated microglial cells and ameliorated the DM-induced decline in astrocyte expression levels in the SDH. However, only the rats treated with cilo-100 demonstrated significant improvements to the aberrant NaV expression in the DRG. Conclusion: Oral cilostazol can blunt the responses of mechanical allodynia and has the potential to treat diabetic neuropathy by attenuating NaV and glial cell dysregulation.
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spelling pubmed-88043392022-02-02 Cilostazol Ameliorates Peripheral Neuropathic Pain in Streptozotocin-Induced Type I Diabetic Rats Cheng, Kuang-I. Wang, Hung-Chen Tseng, Kuang-Yi Wang, Yi-Hsuan Chang, Chung-Yu Chen, Yi-Jing Lai, Chung-Sheng Chen, Dar-Ren Chang, Lin-Li Front Pharmacol Pharmacology Background: Cilostazol is an antiplatelet agent with vasodilating, endothelial function restoration, and anti-inflammatory effects. This study aims to investigate the efficacy of oral cilostazol for preventing the development of diabetic peripheral neuropathy (DPN). Materials and Methods: Ninety adult male Sprague-Dawley rats were divided into five groups: 1) naïve (control); 2) diabetic (DM); 3) DM receiving 10 mg/kg cilostazol (cilo-10); 4) DM receiving 30 mg/kg cilostazol (cilo-30); and 5) DM receiving 100 mg/kg cilostazol (cilo-100). Hindpaw responses to thermal and mechanical stimuli were measured. Activation of microglia and astrocytes in the spinal dorsal horn (SDH) and expression of NaVs in the dorsal root ganglia (DRG) were examined with Western blots and immunofluorescence. Results: DM rats displayed decreased withdrawal thresholds to mechanical stimuli (mechanical allodynia) and blunted responses to thermal stimuli. In addition, the expression of microglia increased, but astrocytes were reduced in the SDH. Upregulation of Nav −1.1, 1.2, −1.3, −1.6, and −1.7 and downregulation of Nav-1.8 were observed in the DRG. The DM rats receiving cilostazol all returned DM-induced decrease in withdrawal threshold to mechanical stimuli and attenuated neuropathic pain. Additionally, all cilostazol treatments suppressed the level of activated microglial cells and ameliorated the DM-induced decline in astrocyte expression levels in the SDH. However, only the rats treated with cilo-100 demonstrated significant improvements to the aberrant NaV expression in the DRG. Conclusion: Oral cilostazol can blunt the responses of mechanical allodynia and has the potential to treat diabetic neuropathy by attenuating NaV and glial cell dysregulation. Frontiers Media S.A. 2022-01-18 /pmc/articles/PMC8804339/ /pubmed/35115925 http://dx.doi.org/10.3389/fphar.2021.771271 Text en Copyright © 2022 Cheng, Wang, Tseng, Wang, Chang, Chen, Lai, Chen and Chang. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Pharmacology
Cheng, Kuang-I.
Wang, Hung-Chen
Tseng, Kuang-Yi
Wang, Yi-Hsuan
Chang, Chung-Yu
Chen, Yi-Jing
Lai, Chung-Sheng
Chen, Dar-Ren
Chang, Lin-Li
Cilostazol Ameliorates Peripheral Neuropathic Pain in Streptozotocin-Induced Type I Diabetic Rats
title Cilostazol Ameliorates Peripheral Neuropathic Pain in Streptozotocin-Induced Type I Diabetic Rats
title_full Cilostazol Ameliorates Peripheral Neuropathic Pain in Streptozotocin-Induced Type I Diabetic Rats
title_fullStr Cilostazol Ameliorates Peripheral Neuropathic Pain in Streptozotocin-Induced Type I Diabetic Rats
title_full_unstemmed Cilostazol Ameliorates Peripheral Neuropathic Pain in Streptozotocin-Induced Type I Diabetic Rats
title_short Cilostazol Ameliorates Peripheral Neuropathic Pain in Streptozotocin-Induced Type I Diabetic Rats
title_sort cilostazol ameliorates peripheral neuropathic pain in streptozotocin-induced type i diabetic rats
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8804339/
https://www.ncbi.nlm.nih.gov/pubmed/35115925
http://dx.doi.org/10.3389/fphar.2021.771271
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