Sodium nitrate preconditioning prevents progression of the neuropathic pain in streptozotocin-induced diabetes Wistar rats

  • Hajar Oghbaei
  • Gisou Mohaddes
  • GholamReza Hamidian
  • Rana KeyhanmaneshEmail author
Research article



The purpose of the study was to evaluate the possible protective effects of low dose sodium nitrate preconditioning on the peripheral neuropathy in streptozotocin (STZ)-induced diabetic model.


Male Wistar rats were randomly divided into five groups: control (no intervention), control treated sodium nitrate (100 mg/L in drinking water), diabetic (no intervention), diabetic treated NPH insulin (2-4 U), and diabetic treated sodium nitrate (100 mg/L in drinking water). Diabetes was induced by intraperitoneal injection of STZ (60 mg/kg). All interventions were done for 60 days immediately following diabetes confirmation. Thermal and mechanical algesia thresholds were measured by means of hot-plate test, von Frey test, and tail-withdrawal test before the diabetic induction and after diabetes confirmation. At the end of the experiment, serum NOx level and serum insulin level were assessed. Blood glucose concentration and body weight have recorded at the base and duration of the experiment.


Both hypoalgesia, hyperalgesia along with allodynia developed in diabetic rats. Significant alterations including, decrease in tail withdrawal latency (30th day), decreased mechanical threshold (60th day), and an increase in hot plate latency (61st day) were displayed in diabetic rats compared to control rats. Nitrate and insulin preconditioning produced protective effects against diabetes-induced peripheral neuropathy. Data analysis also showed a significant increase in glucose level as well as a considerable reduction in serum insulin and body weight of diabetic rats, which restored by both insulin and nitrate preconditioning.


Sodium nitrate preconditioning produces a protective effect in diabetic neuropathy, which may be mediated by its antihyperglycemic effects and increased serum insulin level.


Nitrate preconditioning Diabetes Peripheral nerve Thermal algesia Mechanical algesia 



This article is a part of database from the investigation entitled “The effect of inorganic nitrate on the prevention and treatment of peripheral diabetic neuropathy in typ-1 diabetic male rats” written by Hajar Oghbaei, Faculty of Medicine, Tabriz University of Medical Sciences and was funded by the student research committee of Tabriz University of Medical Sciences (No. IR.TBZMED. REC.1395.960), Tabriz, Iran.

Compliance with ethical standards

Ethical issues

All of protocols were approved by the Ethics Committee of Animal Research of Tabriz University of Medical Sciences (No. IR.TBZMED.REC.1395.960).

Conflict of interests

Authors declare no conflict of interests.


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Copyright information

© Springer Nature Switzerland AG 2020

Authors and Affiliations

  1. 1.Student Research CommitteeTabriz University of Medical SciencesTabrizIran
  2. 2.Neurosciences Research CenterTabriz University of Medical SciencesTabrizIran
  3. 3.Department of Basic Sciences, Faculty of Veterinary MedicineUniversity of TabrizTabrizIran
  4. 4.Tuberculosis and Lung Diseases Research CenterTabriz University of Medical SciencesTabrizIran
  5. 5.Department of Physiology, Faculty of MedicineTabriz University of Medical SciencesTabrizIran
  6. 6.Neurogenic Inflammation Research CenterMashhad University of Medical SciencesMashhadIran

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