Neuroprotective effect of duloxetine in a mouse model of diabetic neuropathy: Role of glia suppressing mechanisms.

Autor: Tawfik MK; Department of Pharmacology, Faculty of Medicine, Suez Canal University, Ismailia 41522, Egypt., Helmy SA; Department of Cytology and Histology, Faculty of Veterinary Medicine, Suez Canal University, Ismailia 41522, Egypt; Female Collage of Applied Medical Sciences, Bisha University, Bisha, Saudi Arabia., Badran DI; Department of Biochemistry, Faculty of Medicine, Suez Canal University, Ismailia 41522, Egypt., Zaitone SA; Department of Pharmacology and Toxicology, Faculty of Pharmacy, University of Tabuk, Tabuk, Saudi Arabia; Department of Pharmacology and Toxicology, Faculty of Pharmacy, Suez Canal University, Ismailia 41522, Egypt. Electronic address: sawsan_zaytoon@pharm.suez.edu.eg.
Jazyk: angličtina
Zdroj: Life sciences [Life Sci] 2018 Jul 15; Vol. 205, pp. 113-124. Date of Electronic Publication: 2018 May 12.
DOI: 10.1016/j.lfs.2018.05.025
Abstrakt: Aims: Painful diabetic neuropathy (PDN) is one of the most frequent complications of diabetes and the current therapies have limited efficacy. This study aimed to study the neuroprotective effect of duloxetine, a serotonin noradrenaline reuptake inhibitor (SNRI), in a mouse model of diabetic neuropathy.
Main Methods: Nine weeks after developing of PDN, mice were treated with either saline or duloxetine (15 or 30 mg/kg) for four weeks. The effect of duloxetine was assessed in terms of pain responses, histopathology of sciatic nerve and spinal cord, sciatic nerve growth factor (NGF) gene expression and on the spinal expression of astrocytes (glial fibrillary acidic protein, GFAP) and microglia (CD 11 b).
Key Findings: The present results highlighted that duloxetine (30 mg/kg) increased the withdrawal threshold in von-Frey test. In addition, both doses of duloxetine prolonged the licking time and latency to jump in the hot-plate test. Moreover, duloxetine administration downregulated the spinal expression of both CD 11 b and GFAP associated with enhancement in sciatic mRNA expression of NGF.
Significance: The current results highlighted that duloxetine provided peripheral and central neuroprotective effects in neuropathic pain is, at least in part, related to its downregulation in spinal astrocytes and microglia. Further, this neuroprotective effect was accompanied by upregulation of sciatic expression of NGF.
(Copyright © 2018 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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