SLR - July 2019 - Weston Angermeier

The Potential of Transdermal Nitric Oxide Treatment for Diabetic Peripheral Neuropathy and Diabetic Foot Ulcers

Walton, David.  Minton, Stephen D.  Cook, Alonzo D. The Potential of Transdermal Nitric Oxide Treatment for Diabetic Peripheral Neuropathy and Diabetic Foot Ulcers. Diabetes & Metabolic Syndrome: Clinical research and reviews xxx (2018) 1-4

Scientific Literature Review

Reviewed By: Weston Angermeier, DPM
Residency Program: MetroWest Medical Center – Farmington, MA

Podiatric Relevance: Diabetic foot ulcers are one of the most prevalent pathologies in podiatry, and we are constantly looking for new ways to improve the care and treatment of these. Many of these DFUs have a non healing component due to lack of blood flow, which is where nitric oxide comes into play. Nitric oxide is a vasodilator that when applied locally, can increase blood flow to these non-healing areas. As shown in this review, diabetic patients skin and nerves have decreased levels of nitrogen oxide synthase, which can contribute to microvascular disease, which then contributes to non-healing ulcers in diabetic peripheral neuropathy.  

Methods: Endothelial nitric oxide synthase, also called eNOS, produces nitric oxide from L-arginine which causes vasodilation. Due to the dysfunction of endothelial cells in patients with diabetic neuropathy, it is theorized that nitric oxide applied topically could improve their symptoms and pain. Skin biopsies were taken from the dorsum of the foot of 36 patients. Immunostaining of eNOS was then performed on both neuropathic and control subjects. Also, fluorescent immunohistochemistry was performed on the sciatic nerve for eNOS in diabetic saline sham and in non-diabetic control mice.  

Results: The immunostaining revealed that eNOS was significantly reduced or absent in the biopsies from neuropathic patients from the control group. Thirteen of the 15 neuropathic patient biopsies had reduced eNOS, while only four of eleven of the control group biopsies had reduced eNOS. Additionally, there was a 40 percent reduction in eNOS of the sciatic nerve when the control group mice were compared to the diabetic animal.

Conclusions: Nitric Oxide is a promising treatment in the future of treatment of DFUs as well as in the treatment of painful symptoms of diabetic neuropathy. It has long been a well-known vasodilator, but there is not much research about its application in the realm of diabetic foot treatment. The use of transdermal nitric oxide would improve the microvascular disease of a diabetic foot, which in turn, could improve wound healing, as well as help prevent or even improve symptoms of diabetic neuropathy. An increase of blood flow to the area would promote overall sensory nerve health as well. Nitric oxide can replenish the diminished eNOS levels in diabetic skin and nerves which are hypothesized to be the cause of neuropathy and microvascular disease. Further studies with larger sample sizes are warranted in the future due to the low risk with topical administration of Nitric Oxide as a potential treatment for diabetic foot ulcers and diabetic peripheral neuropathy.  

Educational Opportunities