Pain Perception and the Autonomic Nervous System

Influences of the Autonomic Nervous System on Experimental Pain Sensitization

In this study, we want to investigate how pain processing and sensation are related to a certain part of the nervous system, the so-called autonomic nervous system.

For this purpose, we apply heat and pressure stimuli to the skin and test pain processing by means of ratings scales and sensory tests. Breathing, heart rate and sweat response are also measured. To assess the spinal cord level, we measure muscle response (measured by electromyography, EMG) to electrical stimulation. Additionally, sensory nerves will be stimulated at the ear and participants will also be given various questionnaires to complete.

Study Overview

• Status: Not yet recruiting
• Conditions: Central Sensitization; Pain Perception; Vagus Nerve Stimulations; Autonomic Nervous System Modulation; Pain Sensitivity
• Intervention / Treatment: Other: respiratory gated taVNS; Other: random burst stimulation; Other: continuous stimulation; Other: Sham stimulation

Detailed Description

This study investigates the effects of autonomic regulation on pain perception and experimentally induced pain sensitivity. Participants come for one or two study visits, that will last approximately 3 hours. The study is divided into two phases: the pilot phase and the main experimental phase.

During the pilot phase, the perception of pressure and heat stimuli, as well as spinal excitability, will be assessed before and during different types of electrical stimulation of sensory nerves at the outer ear.

During the main experimental phase, skin sensitivity and spinal excitability will be assessed before and after repetitive heat stimulation and stimulation of sensory nerves at the outer ear.

In both study phases, the activity of the autonomic nervous system will be assessed throughout the experiment, and questionnaires will be completed.

• Study Type: Interventional
• Enrollment (Estimated): 146
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Petra Schweinhardt, PhD, M Chiro Med; Phone Number: +41 443865724; Email: petra.schweinhardt@balgrist.ch
• Study Contact Backup: Name: Madeleine Hau; Phone Number: +41 443865711; Email: madeleine.hau@balgrist.ch

Study Locations

• Switzerland
  • Zurich, Switzerland, 8008
    • Balgrist University Hospital
    • Contact: Madeleine Hau; Phone Number: +41 44 386 57 11; Email: madeleine.hau@balgrist.ch

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Over 18 and below 40 years of age
2. Good general health
3. Able to give informed consent

Exclusion Criteria:

1. Any major medical or psychiatric condition (e.g. heart disease, diabetes, autoimmune disorders, infectious diseases, major depressive disorder), any chronic pain condition, any respiratory problems, any acute pain at time of study
2. Inability to follow study instructions, e.g. due to language problems
3. Pregnancy (female participants will be asked if pregnancy could be possible)
4. Increased alcohol (>2 (for women)/4 (for men) standard glasses per day or >5 (for women)/4 (for men) glasses at least once a month within a few hours) or caffeine consumption (≥ 400mg per day)
5. Consumption of alcohol, drugs, analgesics within the last 24 h
6. Consumption of more than 100 mg of caffeine within the last 8 h
7. Scar tissue or generally reduced sensitivity in the designated testing site areas
8. Shoe size < 38 (if experiment is conducted at the feet)
9. History of cardiovascular disease or carotid artery disease
10. Medication or Substances inferring with the autonomic nervous system or with pain sensitivity (e.g. Benzodiazepines, Nicotine)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: taVNS; Electrodes will be attached to the outer ear. Electrical stimulation pulses with a width of 250ms will be applied at a frequency of 25Hz. Stimulation intensity will be individually adjusted to be clearly perceived but not painful.	Other: respiratory gated taVNS; Electrical stimulation will be delivered in bursts during expiration; Other: random burst stimulation; Electrical stimulation will be delivered in bursts at random timepoints during the breathing cycle; Other: continuous stimulation; Electrical stimulation will be delivered continuously for 30sec followed by a 30sec break.
Sham Comparator: Sham stimulation; Electrodes will be attached to the outer ear at a different position as for the taVNS. Electrical stimulation pulses with a width of 250ms will be applied at a frequency of 25Hz. Stimulation intensity will be individually adjusted to be clearly perceived but not painful.	Other: Sham stimulation; Electrical stimulation will be identical to the taVNS, but the electrodes will be placed at a different position on the ear

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Magnitude of the Nociceptive Withdrawl Reflex	Muscle responses of the biceps fermoris to an electrical stimulation of the sural nerve will be measured using an electromyogramm	Before, during, and/or immediately after the intervention

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area of Secondary Hyperalgesia	Von Frey filaments will be used to assess the spatial extent of experimentally induced hyperalgesia	Before and 20 min after the intervention
Changes of Pressure Pain Threshold	Pressure will be applied over the thenar eminance of the hand until the participant reports a painful sensation	Before, during, and/or immediately after the intervention
Perceived Pain Intensity and Unpleasantness	Perceived intensity and unpleasantness of heat stimuli will be assessed using rating scales. The intensity rating scale ranges from 0, indicating no perception, to 100, indicating the pain threshold, and up to 200, indicating the most tolerable pain. The unpleasantness rating scale ranges from -100 for 'extremely unpleasant,' through 0 for 'neutral,' to 100 for 'extremely pleasant.	Before, during, and/or immediately after the intervention
Change in Autonomic Nervous System Activity	The activity of the autonomic nervous system will be measures using electrocardiogramm and galvanic skin response	Before, during, and up to 2 min after the intervention.

Collaborators and Investigators

• Sponsor: Schweinhardt Petra
• Investigators: Principal Investigator: Petra Schweinhardt, PhD, M Chiro Med, Balgrist University Hospital, University of Zurich, Zurich, Switzerland

Study record dates

Study Major Dates

• Study Start (Estimated): November 4, 2024
• Primary Completion (Estimated): August 1, 2026
• Study Completion (Estimated): August 1, 2026

Study Registration Dates

• First Submitted: September 6, 2024
• First Submitted That Met QC Criteria: October 30, 2024
• First Posted (Actual): October 31, 2024

Study Record Updates

• Last Update Posted (Actual): October 31, 2024
• Last Update Submitted That Met QC Criteria: October 30, 2024
• Last Verified: August 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Hypersensitivity
• Other Study ID Numbers: taVNS

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Data of participants who gave informed consent for further use of their anonymized data will be made available upon request.
• IPD Sharing Time Frame: The PID, the study protocol and the analytical code will be available after publication for a maximum duration of 10 years
• IPD Sharing Access Criteria: PID will be made available for research purposes only. Anonymized data of all outcome measures can be made available upon request to the sponsor-investigator.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; ANALYTIC_CODE

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No