Focused Ultrasound Improves Microcirculation to Treat Painful Peripheral Neuropathy in Type 2 Diabetic Rats

Focused ultrasound (FUS) has emerged as a noninvasive modality to improve peripheral circulation and nerve function. However, its therapeutic effects on diabetic peripheral neuropathy (DPN) in type 2 diabetes (T2D) remain unclear. Here, we evaluated the efficacy of FUS in a T2D rat model induced by a high-fat diet and low-dose streptozotocin. FUS was applied to the plantar artery. Real-time sonographic imaging and laser Doppler flowmetry assessed arterial flow and toe skin perfusion, respectively. Behavioral pain tests of mechanical allodynia and thermal hyperalgesia, along with histological analysis of intraepidermal microvessels and nerve fibers, were performed. A single FUS session significantly increased arterial flow and toe skin perfusion by approximately twofold, with effects lasting up to 3 min. Two-week FUS treatments significantly enhanced skin perfusion (n = 8 and p < 0.05), capillary density (n = 5 and p < 0.05), and nerve fiber density (n = 5 and p < 0.05) while reducing pain behaviors (n = 8 and p < 0.05). Compared with the previous type 1 DPN study, type 2 DPN rats exhibited greater perfusion recovery (+ 109% versus + 51%) and higher peripheral nerve fiber density (+ 81% versus + 58%). These differences likely reflect distinct neuropathic mechanisms, with T1D primarily involving axonal degeneration and T2D characterized by microvascular dysfunction and metabolic impairment. Thermal measurements confirmed FUS-localized heating remained within safe thresholds, and no tissue damage was observed. These findings suggest that FUS elicits distinct, beneficial vascular responses between T1D and T2D models, supporting its potential as a targeted therapy for painful DPN.