title: Prophylactic L-arginine and ibuprofen delay the development of tactile allodynia and suppress spinal miR-155 in a rat model of diabetic neuropathy.
abstract: 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.
authors.affiliation: Department of Pharmacology, Faculty of Medicine, Ain Shams University, Cairo, Egypt.
authors.forename: Ghada M
authors.initials: GM
authors.lastname: El-Lithy
authors.affiliation: Department of Pharmacology, Faculty of Medicine, Ain Shams University, Cairo, Egypt.
authors.forename: Wesam M
authors.initials: WM
authors.lastname: El-Bakly
authors.affiliation: Department of Biochemistry, Faculty of Medicine, Ain Shams University, Cairo, Egypt.
authors.forename: Marwa
authors.initials: M
authors.lastname: Matboli
authors.affiliation: Department of Histology and Cell Biology, Faculty of Medicine, Ain Shams University, Cairo, Egypt.
authors.forename: Hadwa A
authors.initials: HA
authors.lastname: Abd-Alkhalek
authors.affiliation: Department of Pharmacology, Faculty of Medicine, Ain Shams University, Cairo, Egypt.
authors.forename: Somaia I
authors.initials: SI
authors.lastname: Masoud
authors.affiliation: Department of Pharmacology, Faculty of Medicine, Ain Shams University, Cairo, Egypt. Electronic address: mayhamza2@yahoo.com.
authors.forename: May
authors.initials: M
authors.lastname: Hamza
mesh_terms: D000818:Animals; D001120:Arginine / Q000494:pharmacology / Q000627:therapeutic use*; D003921:Diabetes Mellitus, Experimental / Q000235:genetics / Q000473:pathology; D003929:Diabetic Neuropathies / Q000150:complications / Q000188:drug therapy* / Q000235:genetics* / Q000517:prevention & control; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000187:drug effects / Q000235:genetics; D004359:Drug Therapy, Combination; D005260:Female; D006930:Hyperalgesia / Q000150:complications / Q000188:drug therapy* / Q000235:genetics / Q000517:prevention & control*; D007052:Ibuprofen / Q000494:pharmacology / Q000627:therapeutic use*; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D009132:Muscles / Q000187:drug effects / Q000473:pathology; D009569:Nitric Oxide / Q000378:metabolism; D010523:Peripheral Nervous System Diseases / Q000188:drug therapy / Q000235:genetics; D017208:Rats, Wistar; D012867:Skin / Q000187:drug effects / Q000473:pathology; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D013311:Streptozocin; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics
chemical_list: C580597:MIRN155 microRNA, rat; D035683:MicroRNAs; D009569:Nitric Oxide; D013311:Streptozocin; D001120:Arginine; D007052:Ibuprofen