Wearable Focused Ultrasound Stimulation for Peripheral Nerve Pain Management (PERNEUS)

Focused Ultrasound Stimulation of Peripheral Nerves in Limbs

This study will evaluate the feasibility of a novel wearable focused ultrasound (FUS) device for peripheral nerve stimulation in healthy volunteers. The aim is to assess device operability, usability, tolerability, and physiological responses during standardized sensory tests. Each participant will complete nine ~1-hour study sessions across multiple days, including cold pressor and algometry tasks performed under baseline, sham, and active FUS conditions.

Study Overview

• Status: Completed
• Conditions: Pain Management; Peripheral Neuropathic Pain
• Intervention / Treatment: Device: Cold Pressor Task - Upper Limb; Device: Algometry Pain Tests in the Upper Limb; Device: Algometry Pain Tests in the Lower Limb

Detailed Description

This feasibility study will evaluate a wearable focused ultrasound (FUS) system designed for non-invasive peripheral nerve stimulation of upper and lower extremity nerves. The primary objective is to determine device feasibility - operability, tolerability, usability, and physiological responses - during standardized pain sensitivity tasks.

Each participant will complete nine sessions on separate days (~1 hour each) in a within-subject crossover design:

1. Cold pressor test (baseline, sham, active FUS) - 3 days
2. Upper limb algometry (baseline, sham, active FUS) - 3 days
3. Lower limb algometry (baseline, sham, active FUS) - 3 days

Sessions will be scheduled at least 24 hours apart to avoid carryover effects. Approximately 12-15 participants will be enrolled. Although feasibility studies often include fewer than 10 participants, this sample size was chosen to ensure variability across limb anatomy and usability testing. No efficacy hypotheses or clinical outcomes will be tested.

• Study Type: Interventional
• Enrollment (Actual): 8
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Texas
    • Austin, Texas, United States, 78705
      • Biomedical Enginering Building - UT Austin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

- Healthy adults aged 20-40, willing and able to undergo FUS experiments.

Exclusion Criteria:

• Major physical illnesses.
• Diagnosis of a cognitive disorder.
• Cardiovascular conditions (e.g., high blood pressure, heart disease, or dysrhythmia), history of fainting or seizures, or history of frostbite.
• Open cuts, sores, or bone fractures on the limb to be immersed in water, or a history of Raynaud's phenomenon.
• Diagnosis of hypersensitivity or hyposensitivity to bodily sensations (temperature, vibrotactile, nociception).
• Inability to provide informed consent for FUS stimulation.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Device Feasibility
• Allocation: Non-Randomized
• Interventional Model: Crossover Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Active Focused Ultrasound (FUS) Stimulation; Participants will receive active focused ultrasound stimulation applied to peripheral nerves (radial, median, ulnar, tibial, saphenous, or peroneal) using a wearable FUS device. Stimulation will be performed during pain sensitivity assessments, including cold pressor tests and pressure algometry, to record pain perception/thresholds as exploratory physiological responses during feasibility testing.	Device: Cold Pressor Task - Upper Limb; This study uses a three-session cold pressor paradigm to evaluate feasibility of a wearable focused ultrasound (FUS) device for peripheral nerve stimulation. Session 1 (Baseline): After consent, participants immerse the dominant hand in 0-1 °C water (~10 cm depth) in an insulated bucket. Time to first pain is recorded, with 5 min rests between immersions (12 total; max single immersion 6 min). Water temperature is digitally monitored, with ice added as needed. Session 2 (Sham): The median/ulnar/radial nerve in the dominant forearm is located by ultrasound. The FUS device is applied with hydrogel but set to sham (no output). The cold pressor protocol is repeated. Session 3 (Active FUS): After nerve localization, active FUS (650 kHz, 60-100% intensity, 20-30% duty cycle) is delivered for 5 min. The cold pressor test is repeated to record pain tolerance as an exploratory physiological response during feasibility testing.; Device: Algometry Pain Tests in the Upper Limb; This session records pressure pain thresholds in the dominant hand with a wearable FUS device and a pressure algometer during feasibility testing. Session 1 (Baseline): After consent and briefing, the median, ulnar, and radial nerves at three points on the dominant hand (wrist, palm, finger) are located via ultrasound and marked. A pressure algometer is applied to each site, with pressure gradually increased until pain is first reported. Thresholds are recorded, with each location tested three times with short breaks. Session 2 (Sham): The same nerve sites are identified and marked. The wearable FUS device is applied with hydrogel but set to sham (no active output). The baseline algometry protocol is repeated. Session 3 (Active FUS): Following nerve localization, active FUS (650 kHz, 60-100% intensity, 20-30% duty cycle) is delivered for 5 min. The algometry test is repeated to record pressure pain thresholds as exploratory physiological responses during feasibility testing.; Device: Algometry Pain Tests in the Lower Limb; This session records pressure pain thresholds in the dominant foot with a wearable FUS device and a pressure algometer during feasibility testing. Session 1 (Baseline): After consent and briefing, the tibial, saphenous, and peroneal nerves at three standardized points on the dominant foot are located via ultrasound and marked. A pressure algometer is applied to each site, and pressure is gradually increased until pain is first reported. Thresholds are recorded, with repeated trials and short breaks between tests. Session 2 (Sham): The same nerve sites are identified and marked. The wearable FUS device is applied with hydrogel but set to sham (no active output). The baseline algometry protocol is repeated. Session 3 (Active FUS): Following nerve localization, active FUS (650 kHz, 60-100% intensity, 20-30% duty cycle) is delivered for 5 min. The algometry test is then repeated to record pressure pain thresholds as exploratory physiological responses during feasibility testing.
Sham Comparator: Sham Focused Ultrasound (FUS) Stimulation; Participants will undergo the same procedures as the experimental arm (device placement, cold pressor test, and pressure algometry) but with the FUS device set to sham (no active ultrasound output). This arm is used to control for placebo and non-specific effects of device application during pain sensitivity assessments.	Device: Cold Pressor Task - Upper Limb; This study uses a three-session cold pressor paradigm to evaluate feasibility of a wearable focused ultrasound (FUS) device for peripheral nerve stimulation. Session 1 (Baseline): After consent, participants immerse the dominant hand in 0-1 °C water (~10 cm depth) in an insulated bucket. Time to first pain is recorded, with 5 min rests between immersions (12 total; max single immersion 6 min). Water temperature is digitally monitored, with ice added as needed. Session 2 (Sham): The median/ulnar/radial nerve in the dominant forearm is located by ultrasound. The FUS device is applied with hydrogel but set to sham (no output). The cold pressor protocol is repeated. Session 3 (Active FUS): After nerve localization, active FUS (650 kHz, 60-100% intensity, 20-30% duty cycle) is delivered for 5 min. The cold pressor test is repeated to record pain tolerance as an exploratory physiological response during feasibility testing.; Device: Algometry Pain Tests in the Upper Limb; This session records pressure pain thresholds in the dominant hand with a wearable FUS device and a pressure algometer during feasibility testing. Session 1 (Baseline): After consent and briefing, the median, ulnar, and radial nerves at three points on the dominant hand (wrist, palm, finger) are located via ultrasound and marked. A pressure algometer is applied to each site, with pressure gradually increased until pain is first reported. Thresholds are recorded, with each location tested three times with short breaks. Session 2 (Sham): The same nerve sites are identified and marked. The wearable FUS device is applied with hydrogel but set to sham (no active output). The baseline algometry protocol is repeated. Session 3 (Active FUS): Following nerve localization, active FUS (650 kHz, 60-100% intensity, 20-30% duty cycle) is delivered for 5 min. The algometry test is repeated to record pressure pain thresholds as exploratory physiological responses during feasibility testing.; Device: Algometry Pain Tests in the Lower Limb; This session records pressure pain thresholds in the dominant foot with a wearable FUS device and a pressure algometer during feasibility testing. Session 1 (Baseline): After consent and briefing, the tibial, saphenous, and peroneal nerves at three standardized points on the dominant foot are located via ultrasound and marked. A pressure algometer is applied to each site, and pressure is gradually increased until pain is first reported. Thresholds are recorded, with repeated trials and short breaks between tests. Session 2 (Sham): The same nerve sites are identified and marked. The wearable FUS device is applied with hydrogel but set to sham (no active output). The baseline algometry protocol is repeated. Session 3 (Active FUS): Following nerve localization, active FUS (650 kHz, 60-100% intensity, 20-30% duty cycle) is delivered for 5 min. The algometry test is then repeated to record pressure pain thresholds as exploratory physiological responses during feasibility testing.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Completion Rate of Study Sessions	Proportion of participants who complete all nine planned sessions (baseline, sham, active FUS for cold pressor, upper limb algometry, and lower limb algometry) without withdrawal or device malfunction.	Through study completion (9 study visits over approximately 3 weeks).

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cold Pressor Pain Onset Time	Time (seconds) from immersion of the hand in ice water until pain is first reported; measured during baseline, sham, and active FUS sessions to characterize physiological response during feasibility testing (not powered for efficacy).	3 separate study visits (~1 hour each) over approximately 1 week.
Upper Limb Algometry Pain Threshold	Maximum tolerated pressure (kgf) at standardized points on the hand and forearm before pain is reported, measured using a pressure algometer during baseline, sham, and active FUS sessions. Recorded as an exploratory physiological response during feasibility testing.	3 separate study visits (~1 hour each) over approximately 1 week.
Lower Limb Algometry Pain Threshold	Maximum tolerated pressure (kgf) at standardized points on the foot before pain is reported, measured using a pressure algometer during baseline, sham, and active FUS sessions. Recorded as an exploratory physiological response during feasibility testing.	3 separate study visits (~1 hour each) over approximately 1 week.

Collaborators and Investigators

• Sponsor: Evan (Huiliang) Wang
• Investigators: Principal Investigator: Huiliang Wang, PhD, University of Texas at Austin

Publications and helpful links

General Publications

• Legon W, Rowlands A, Opitz A, Sato TF, Tyler WJ. Pulsed ultrasound differentially stimulates somatosensory circuits in humans as indicated by EEG and FMRI. PLoS One. 2012;7(12):e51177. doi: 10.1371/journal.pone.0051177. Epub 2012 Dec 4.
• Dickey TC, Tych R, Kliot M, Loeser JD, Pederson K, Mourad PD. Intense focused ultrasound can reliably induce sensations in human test subjects in a manner correlated with the density of their mechanoreceptors. Ultrasound Med Biol. 2012 Jan;38(1):85-90. doi: 10.1016/j.ultrasmedbio.2011.09.020. Epub 2011 Nov 21.

Study record dates

Study Major Dates

• Study Start (Actual): July 14, 2025
• Primary Completion (Actual): September 15, 2025
• Study Completion (Actual): October 15, 2025

Study Registration Dates

• First Submitted: July 25, 2025
• First Submitted That Met QC Criteria: August 28, 2025
• First Posted (Actual): September 8, 2025

Study Record Updates

• Last Update Posted (Actual): June 10, 2026
• Last Update Submitted That Met QC Criteria: June 8, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: Peripheral Nerve Stimulation; Pain Threshold; Focused Ultrasound; Pain Modulation; Saphenous Nerve; Tibial Nerve; Non-Invasive Neuromodulation; Wearable Neurotechnology; Radial Nerve; Experimental Pain Testing; Ultrasound Neuromodulation
• Additional Relevant MeSH Terms: Neurologic Manifestations; Nervous System Diseases; Neurobehavioral Manifestations; Perceptual Disorders; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Agnosia
• Other Study ID Numbers: STUDY00005942

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes