PNS to Improve Vascular Function and Limb Health in Veterans

Peripheral Neural Stimulation to Improve Microvascular Function and Limb Health in Veterans With Diabetic Peripheral Neuropathy

Establishing a sensitive, scalable physiological test for neurovascular reflex integrity and investigating whether targeted peripheral neural stimulation can enhance perfusion and vasodilatory responsiveness.

The overarching goal of this project is to define how targeted afferent activation can be used to restore impaired neurovascular reflexes, improve skin perfusion, and ultimately prevent further decline in limb health in Veterans. By integrating functional and structural imaging with neural modulation, this work will establish foundational evidence for diagnostic and therapeutic strategies aimed at early detection of neurovascular decline and prevention of tissue breakdown in both Diabetic Peripheral Neuropathy (DPN) and residual-limb contexts. Furthermore, this work will establish the feasibility of preventing or delaying the mechanical trauma of the insensate distal limb which invariably leads to deep pressure injuries, infections, and amputation in Veterans with DPN. The findings have the potential to transform care by enabling earlier diagnosis, improving neurovascular responsiveness, and optimizing neuromodulation protocols to prevent skin complications, delay progression toward amputation, and improve quality of life in Veterans with DPN or limb loss.

Inclusion Criteria:

Inclusion Criteria - All Participants:

• English-speaking
• Veteran

Inclusion Criteria - Diabetic Peripheral Neuropathy (DPN) Participants:

• Confirmed diagnosis of type 1 or type 2 diabetes mellitus for at least 5 years
• Clinical signs and/or symptoms consistent with diabetic peripheral neuropathy Or confirmation of neuropathy via physical exam

Inclusion Criteria - Lower Limb Amputees:

• Unilateral transtibial or transfemoral amputation
• Medically stable for at least 3 months
• For the designated subset of the limb-loss cohort (n = 6): implanted with C-FINEs on the sciatic and/or tibial nerves

Exclusion Criteria:

Exclusion Criteria - All Participants:

• Severe neurological disorders impairing ambulation
• Visual or hearing impairments interfering with study participation
• Cardiovascular or respiratory conditions posing risk during participation
• Cognitive or psychiatric conditions compromising informed consent
• Participation in other clinical trials interfering with outcomes
• Pregnancy
• History of photosensitivity or known sensitivity to laser light

Additional Exclusion Criteria - Amputees:

• Active skin breakdown or infection at residual limb
• Significant phantom or residual limb pain interfering with study procedures
• Bilateral lower-limb amputation