The Combined Effect of TENS and TaVNS on Pressure and Heat Pain Thresholds in Pain-Free Subjects

The Combined Effect of Transcutaneous Electrical Nerve Stimulation and Transcutaneous Auricular Vagus Nerve Stimulation on Pressure and Heat Pain Thresholds in Pain-Free Subjects: A Randomized Cross-Over Trial

Transcutaneous electrical nerve stimulation (TENS) is a non-invasive modality that utilizes electrical currents to modulate pain in populations with acute and chronic pain. TENS has been demonstrated to produce hypoalgesic effects in postoperative pain, fibromyalgia, knee osteoarthritis, and healthy subjects. Transcutaneous auricular vagus nerve stimulation (TaVNS) is a non-invasive modality that modulates the vagus nerve by stimulating its auricular branches. The effects of the combination of TENS and TaVNS on producing an analgesic response have not been studied. Considering that TENS and TaVNS both stimulate similar analgesic pathways but through different means of activation, the investigators can hypothesize that a combination of both methods can produce a more pronounced analgesic response. Therefore, the objective of this study is to assess the hypoalgesic effect of a combination of TENS and TaVNS in pain-free subjects.

The study will be a simple crossover design conducted at the University of Hartford. Subjects will be recruited from the University of Hartford population via oral communication, digital flyers, and posters on campus. Thirty participants will undergo two sessions in a crossover manner with one week in between. During one session, the participants will receive TENS with active TaVNS and the other session will be a placebo procedure (TENS with placebo TaVNS). The order of these sessions will be randomized. Importantly, the pressure pain threshold (PPT) and heat pain threshold (HPT) assessors will be blinded to the treatment category. For active TaVNS, a frequency of 25 Hz will be applied with a pulse duration of 200 µs. For placebo TaVNS, the intensity will be increased to a sensory level and then decreased to 0 mA. High frequency TENS of 100Hz will be applied in both sessions, with a pulse duration of 200 µsec, asymmetrical biphasic square waveform, and intensity of maximal tolerance without pain. TENS and TaVNS will be turned on for 30 minutes after a baseline measurement of outcomes. TENS and TaVNS will then be turned off, but the electrodes will remain on until completion of post-treatment assessment. Pressure pain threshold, heat pain threshold, blood pressure, oxygen saturation and heart rate will be tested 4 times: Once pre-intervention, once during intervention, once immediately after the intervention and once 15 minutes post-intervention.

Study Overview

• Status: Completed
• Conditions: Healthy Volunteers
• Intervention / Treatment: Device: Active Transcutaneous Auricular Vagus Nerve Stimulation (TaVNS); Device: Transcutaneous Electrical Nerve Stimulation; Device: Placebo Transcutaneous Auricular Vagus Nerve Stimulation (TaVNS)

Detailed Description

The study will be a simple crossover design with the following two treatments: (1) active TaVNS and (2) placebo TaVNS. Each subject will receive both interventions in random order.

Pressure and Heat pain thresholds will be recorded at baseline, 15 min, 30 min, and 45 min.

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Connecticut
    • West Hartford, Connecticut, United States, 06117
      • University of Hartford

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Absence of pain
• Age 18-40
• Men and women

Exclusion Criteria:

• Neurological diseases
• Severe cardiorespiratory disease
• Pregnancy
• Skin infection or lesions or change in sensation at the TENS or TaVNS application site
• Cancer
• Cardiac pacemaker
• Allergy to electrodes
• Chronic illness or pain
• Use of drugs that affect pain or vagal tone in the past 48 hours prior to data collection

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Active TaVNS; Active TaVNS: frequency of 25 Hz, pulse duration of 200 µs, at a strong but comfortable intensity.	Device: Active Transcutaneous Auricular Vagus Nerve Stimulation (TaVNS); Both concha will be swabbed with an alcohol wipe before applying a thin layer of conductive gel. An ear clip electrode will be placed in the concha of both ears. A frequency of 25 Hz will be applied with a pulse duration of 200 µs. Every 5 minutes, the subject will be asked if the intensity can be increased, decreased or remain the same to maintain the same level of intensity. Participants will also receive active TENS, 100 Hz, 200 µsec on forearm.; Other Names: TaVNS; Device: Transcutaneous Electrical Nerve Stimulation; TENS will be applied on subject's forearm at a strong but comfortable intensity; Other Names: TENS
Placebo Comparator: Placebo TaVNS; Placebo TaVNS: the intensity will be increased to a sensory level and then decreased to 0 mA	Device: Transcutaneous Electrical Nerve Stimulation; TENS will be applied on subject's forearm at a strong but comfortable intensity; Other Names: TENS; Device: Placebo Transcutaneous Auricular Vagus Nerve Stimulation (TaVNS); For placebo TaVNS, the intensity will be increased to a sensory level and then decreased to 0 mA. Participants will also receive active TENS, 100 Hz, 200 µsec on forearm.; Other Names: Placebo TaVNS

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pressure Pain Threshold	A digital pressure algometer will measure the pain threshold to deep mechanical stimuli in kPa	2 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Heat Pain Threshold	Superficial heat pain sensitivity, in degree Celsius, will be assessed using a handheld thermode.	2 weeks
Heart rate	Heart rate (beats per minute) will be assessed using a fingertip pulse oximeter	2 weeks
Oxygen saturation	Oxygen saturation in percentage will be assessed using a fingertip pulse oximeter	2 weeks
Blood pressure	Systolic and Diastolic Blood pressure in millimeters of mercury will be assessed using a upper arm cuff, blood pressure monitor	2 weeks

Collaborators and Investigators

• Sponsor: University of Hartford
• Investigators: Principal Investigator: Richard E Liebano, PhD, University of Hartford

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2024
• Primary Completion (Actual): July 20, 2024
• Study Completion (Actual): October 20, 2024

Study Registration Dates

• First Submitted: March 25, 2024
• First Submitted That Met QC Criteria: April 9, 2024
• First Posted (Actual): April 11, 2024

Study Record Updates

• Last Update Posted (Estimated): December 6, 2024
• Last Update Submitted That Met QC Criteria: December 3, 2024
• Last Verified: December 1, 2024

More Information

Terms related to this study

• Keywords: Transcutaneous Auricular Vagus Nerve Stimulation; Transcutaneous Electric Nerve Stimulation; Pain Threshold; Pain Measurement; Randomized cross-over trial
• Other Study ID Numbers: 24-01-281

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
• product manufactured in and exported from the U.S.: No