How muscle reflexes and antioxidants affect walking pain and blood pressure in peripheral artery disease

Nrf2 and the exaggerated Exercise Pressor Reflex in Peripheral Arterial Disease

NIH-funded research University of Nebraska Medical Center · NIH-11237160

This project seeks to find out whether blocking a muscle nerve reflex and boosting the Nrf2 antioxidant system can reduce blood pressure spikes, improve muscle blood flow, and ease walking pain for people with peripheral artery disease.

Quick facts

Grant typeR01 grant
Study typeNIH-funded research
Funding institutionUniversity of Nebraska Medical Center NIH-funded
Lab location1 site (Omaha, United States)
Project IDNIH-11237160 on NIH RePORTER

What this research studies

Researchers will use a rat model that mimics peripheral artery disease to reproduce the walking-related leg pain and measure heart rate, blood pressure, and muscle blood flow during static and dynamic exercise. They will compare animals with PAD to sham controls and score pain-related behaviors to see how an exaggerated muscle reflex links to reduced blood flow and pain. The team will use a targeted drug (resiniferatoxin) to silence the TRPV1-containing muscle afferent reflex and test whether this improves muscle perfusion and lowers reflex-driven blood pressure rises. They will also study the Nrf2 antioxidant pathway to see whether modifying it protects muscle and reduces the reflex response that may lead to claudication.

Who could benefit from this research

Good fit: People with peripheral arterial disease who experience intermittent claudication (walking-induced leg pain and limited walking ability) would be the most relevant candidates for related future human studies.

Not a fit: People without PAD or whose leg pain comes from non-vascular causes (for example, arthritis or certain nerve disorders) are unlikely to benefit from this approach.

Why it matters

Potential benefit: If successful, this work could point to new treatments that reduce exercise-induced blood pressure spikes and leg pain so people with PAD can walk farther and have better quality of life.

How similar studies have performed: Previous animal studies targeting TRPV1-expressing muscle afferents and modulating Nrf2 have shown promising effects on reflex activity and tissue protection, but these strategies have not yet been proven in humans.

Where this research is happening

Omaha, United States

Researchers

About this research

  1. This is an active NIH-funded research project — typically early-stage science, not a clinical trial accepting patient enrollment.
  2. Some NIH-funded labs run parallel clinical studies or seek volunteers for related work. To check, contact the principal investigator or institution listed above.
  3. For full project details, budget, and progress reports, visit the official NIH RePORTER page below.
Conditions Animal Disease Models
Last reviewed 2026-06-13 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.