Acute Hypoglycemia Induces Painful Neuropathy and the Treatment of Coenzyme Q10.

Yan Ping Zhang,Jinfeng Yang,Yiliam Rodriguez,Keith A Candiotti,Shanshan Mei

doi:10.1155/2016/4593052

Abstract

Diabetic neuropathic pain is reduced with tight glycemic control. However, strict control increases the risk of hypoglycemic episodes, which are themselves linked to painful neuropathy. This study explored the effects of hypoglycemia-related painful neuropathy. Pretreatment with coenzyme Q10 (CoQ10) was performed to explore the preventive effect of CoQ10 on hypoglycemia-related acute neuropathic pain. Two strains of mice were used and 1 unit/kg of insulin was given to induce hypoglycemia. Mechanical sensitivity of hindpaw withdrawal thresholds was measured using von Frey filaments. Blood glucose levels were clamped at normal levels by joint insulin and glucose injection to test whether insulin itself induced hypersensitivity. Results suggest that the increased mechanical sensitivity after insulin injection is related to decreased blood glucose levels. When blood glucose levels remained at a normal level by the linked administration of insulin and glucose, mice demonstrated no significant change in mechanical sensitivity. Pretreatment with CoQ10 prevented neuropathic pain and the expression of the stress factor c-Fos. These results support the concept that pain in the diabetic scenario can be the result of hypoglycemia and not insulin itself. Additionally, pretreatment with CoQ10 may be a potent preventive method for the development of neuropathic pain.

Highlights

Diabetic neuropathy is a leading complication of diabetes mellitus, resulting in significant morbidity and mortality
The Effect of Glycemic Levels on Mechanical Sensitivity after Insulin or Saline Injection. It appeared that decreased blood glucose levels correlated to increased pain in the insulin treatment group
A group of normal saline-injected mice served as a control and demonstrated no changes in blood glucose levels or mechanical sensitivity, indicating that handling and injection stress did not affect or confound results

Summary

Introduction

Diabetic neuropathy is a leading complication of diabetes mellitus, resulting in significant morbidity and mortality. Its exact pathogenesis is not fully understood, hyperglycemia does not appear to be the sole factor in the development of neuropathy in diabetic patients. Neuropathy secondary to rapid normalization of chronic hyperglycemia in the setting of poorly controlled diabetes is emerging as a new disease entity classified as an iatrogenic complication [3]. Symptoms in these patients are typically consistent with a distal sensory polyneuropathy which is appearing shortly after the initiation of intensive glycemic control and is referred to as “insulin neuritis” or treatment-induced neuropathy and is characterized by acute, severe pain [1]. The only available method for preventing this hypoglycemiainduced neuronal injury in the clinical setting is the delivery of glucose, a treatment that paradoxically may exacerbate the insult

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