Article Text
Abstract
Objective Effective treatment methods for diabetic peripheral neuropathy are still lacking. Here, a focused ultrasound (FUS) technique was developed to improve blood flow in diabetic peripheral vessels and potentially treat diabetic peripheral neuropathy.
Research design and methods Male adult Sprague-Dawley rats at 4 weeks poststreptozotocin injections were adopted as models for diabetic neuropathic rats. For single FUS treatment, blood perfusion in the skin of the pad of the middle toe was measured before, during, and after the medial and lateral plantar arteries were treated by FUS. For multiple FUS treatments, blood perfusion measurements, von Frey and hot plate testing and nerve conduction velocity measurements were performed before ultrasonic treatment on the first day of each week, and the microvascular and neural fiber densities in the pad of the toe were measured on the first day of the last week.
Results The blood perfusion rate significantly increased for 7–10 min in the control and neuropathic rats after a single ultrasound exposure. Multiple ultrasound treatments compared with no treatments significantly increased blood perfusion at the second week and further enhanced perfusion at the third week in the neuropathic rats. Additionally, the paw withdrawal force and latency significantly increased from 34.33±4.55 g and 3.96±0.25 s at the first week to 39.10±5.02 g and 4.77±0.71 s at the second week and to 41.13±2.57 g and 5.24±0.86 s at the third week, respectively. The low nerve conduction velocity in the diabetic rats also improved after the ultrasound treatments. Additionally, ultrasound treatments halted the decrease in microvessel and neural fiber densities in the skin of the diabetic toes. Histologic analysis indicated no damage to the treated arteries or neighboring tissue.
Conclusions FUS treatment can increase upstream arterial blood flow in diabetic feet, ameliorate the decrease in downstream microvessel perfusion and halt neuropathic progression.
- ultrasound therapy
- technology and diabetes
- peripheral neuropathy
- novel treatment modalities of complications
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Footnotes
Contributors J-ST performed the experiments and statistical analyses and drafted the manuscript. C-CL contributed to the discussion and reviewed the manuscript. G-SC designed the study, contributed to the discussion and reviewed/edited the manuscript. G-SC is the guarantor of this work and, as such, had full access to all data in the study and takes responsibility for the integrity and accuracy of the data analysis.
Funding This work was supported by the National Health Research Institutes (BN-108-PP-10) and the Ministry of Science and Technology (MOST 105-2221-E-400-004-MY3 and MOST 108-2221-E-400-001) in Taiwan.
Competing interests None declared.
Patient consent for publication Not required.
Ethics approval All animal procedures were approved by the Institutional Animal Care and Use Committee of the National Health Research Institutes in Taiwan (AAALAC accredited).
Provenance and peer review Not commissioned; externally peer reviewed.
Data availability statement All data relevant to the study are included in the article or uploaded as supplementary information.