Prophylactic L-arginine and ibuprofen delay the development of tactile allodynia and suppress spinal miR-155 in a rat model of diabetic neuropathy

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• 作者：Ghada M. El-Lithy^a ; Wesam M. El-Bakly^a ; Marwa Matboli^b ; Hadwa A. Abd-Alkhalek^c ; Somaia I. Masoud^a ; May Hamza^a ; ^{mayhamza2@yahoo.com" class="auth_mail" title="E-mail the corresponding author} ; ^{drmai_hamza@med.asu.edu.eg" class="auth_mail" title="E-mail the corresponding author}
• 关键词：CCI ; Chronic constriction injury ; cDNA ; Complementary DNA ; COX ; Cyclooxygenase enzyme ; DN ; Diabetic neuropathy ; ELISA ; Enzyme-linked immunosorbent assay ; eNOS ; Endothelial nitric oxide synthase ; H&E ; Hematoxylin and eosin ; IL-1β ; Interleukin-1β ; IL-6 ; Interleukin 6 ; iNOS ; Inducible nitric oxide synthase ; miR-155 ; Micro RNA-155 ; NF-κB ; Nuclear factor-κB ; nNOS ; Neuronal nitric oxide synthase ; NO ; Nitric oxide ; NSAIDs ; Nonsteroidal anti-inflammatory drugs ; PCR ; Polymerase chain reaction ; PG ; Prosta
• 刊名：Translational Research
• 出版年：2016
• 出版时间：November 2016
• 年：2016
• 卷：177
• 期：Complete
• 页码：85-97.e1
• 全文大小：1833 K

文摘

Diabetic neuropathy (DN) is a common complication of diabetes mellitus that is hardly reversible at the late stages. Since treatment of neuropathic pain is predominantly symptomatic, a prophylactic measure would be useful. Both ibuprofen and L-arginine exert antiallodynic effects on chronic constriction injury (CCI)-induced cold allodynia. Furthermore, ibuprofen is effective in CCI-induced mechanical allodynia. The aim of the study was to assess the antiallodynic effect of prophylactic ibuprofen and L-arginine in streptozotocin-induced DN in rats and to further investigate the role of spinal miR-155 and nitric oxide (NO) in this effect. Tactile allodynia was assessed weekly by von Frey filaments. Oral daily administration of ibuprofen, L-arginine and their combination, for 4 weeks starting 1 week after streptozotocin injection (ie, before the development of tactile allodynia), resulted in a significant decrease of tactile allodynia compared with the control diabetic group. This was evident in the fifth week of the experiment. The 3 treatments prevented the decrease in muscle fiber diameter and epidermal thickness, seen in the control diabetic group. Furthermore, ibuprofen, L-arginine and their combination prevented the increase in the spinal NO level and miRNA-155, seen in the control diabetic group. In conclusion, both ibuprofen and L-arginine delayed the development of behavioral and histologic changes of DN, with concomitant suppression of spinal miR-155 and NO level. L-arginine being tolerable may be useful prophylactically in diabetic patients.