Pain Processing In Relation To Breathing

Potential Influences of Respiration Patterns on Experimental Pain Sensitization

The goal of this clinical trial is to investigate the effect of breathing on the processing of experimental pain in healthy participants. The main questions are:

1. Does breathing rate influence the spatial extent of thermally induced secondary hyperalgesia, a proxy of central sensitization?
2. Does resonance frequency breathing influence the autonomic nervous system, compared to baseline and compared to paced breathing at a natural frequency?
3. Is spinal excitability, measured using the magnitude of the nociception withdrawal reflex (NWR), affected by resonance frequency breathing, compared to paced breathing at a natural frequency?

Participants:

• will receive heat stimuli
• 's skin's sensitivity will be tested using quantitative sensory testing tools.
• will receive various instructions on the speed of their breathing
• 's heart rate, respiratory rate and sweat response will be measured
• will fill in questionnaires

Researchers will compare the spatial extent of sensitivity resulting from application of heat stimuli during paced resonance frequency breathing compared to paced breathing at a natural frequency to see if the breathing rhythm influences central sensitization processes.

Study Overview

• Status: Recruiting
• Conditions: Pain; Central Sensitisation
• Intervention / Treatment: Behavioral: Paced Resonance Frequency Breathing; Behavioral: Paced Breathing at Natural Frequency; Other: Heat Stimulations

• Study Type: Interventional
• Enrollment (Estimated): 200
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Petra Schweinhardt, Prof. Dr. med; Phone Number: +41 44 510 73 81; Email: petra.schweinhardt@balgrist.ch

Study Locations

• Switzerland
  • Zürich, Switzerland, 8008
    • Recruiting
    • University Hospital Balgrist, University Zürich
    • Contact: Petra Schweinhardt, Prof. Dr. med; Phone Number: +41 44 510 73 81; Email: petra.schweinhardt@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 current acute pain at time of study
2. inability to follow study instructions, e.g. due to language problems
3. Consumption of alcohol, drugs, analgesics within the last 24 h
4. Consumption of no more than 100 mg of caffeine within the last 8 h
5. Scar tissue or generally reduced sensitivity in the designated testing site areas

Additional exclusion criteria for experiments 3 and 4

1. Shoe size < 38
2. Restless-Legs-Syndrome

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Healthy participants; Participants should be aged 18-40, in good health, capable of informed consent, without major medical/psychiatric conditions (e.g., heart disease, diabetes, autoimmune disorders, infectious diseases, major depressive disorder), chronic pain, respiratory issues, or ongoing acute pain, qualify. Exclusions: inability to follow instructions (e.g., language issues), recent alcohol/drug/analgesic use (<24h), caffeine intake (>100mg <8h), or scar tissue/general reduced sensitivity in test areas. Participants undergo three interventions. The heat stimulation intervention is performed twice. During one heat stimulation intervention, participants receive the 'resonance frequency breathing' intervention. During the other heat stimulation intervention, participants receive the 'natural frequency breathing' intervention. The order of the breathing interventions is counterbalanced across participants.

Behavioral: Paced Resonance Frequency Breathing; Participants are required to pace their breathing to their pre-determined individual resonance frequency.; Behavioral: Paced Breathing at Natural Frequency; Participants are required to pace their breathing to their pre-determined individual breathing frequency at rest.; Other: Heat Stimulations; Participants will undergo a heat stimulation procedure on their left and right foot (the order of which is counterbalanced across participants). During this procedure, there are 10 blocks, with an inter-stimulus interval of 30 seconds between two blocks. During a block, six 6-second heat stimulations (48 degrees) are given. Between the stimulations, the temperature quickly returns to baseline (32 degrees).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area of Hypersensitivity surrounding the primary stimulation site	Before and after thermal stimulations, the sensitivity of the skin is tested using a von Frey Filament, a Pin Prick and a brush. Thermal stimulations cause hypersensitivity of the skin, resulting in an area of hypersensitivity surrounding the stimulation site. The primary outcome measure is the amount of change in the area of hypersensitivity from before to after the thermal stimulations. The measuring unit of this outcome is square centimetres.	40 minutes

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Power in the Low-frequency Range of the Heart Rate Variability	Power is measured in units of milliseconds squared (ms 2) for a the low frequency band (Hz), ranging from 0.04 - 0.15Hz	25 minutes
Root Mean Square of Successive Differences of the Heart Rate Variability	The measuring unit to measure heart rate variability is the root mean square of successive differences between normal heartbeats.	25 minutes
Galvanic Skin Potential	Galvanic Skin potential is taken as a reflection of electrodermal activity. The measuring unit of this outcome is microsiemens	25 minutes
Threshold and Magnitude of the Nociceptive Withdrawal Reflex	The nociceptive withdrawal reflex is triggered using an supratheshold electrical stimulation at the nervus suralis leading muscle contraction in the ipsilateral biceps femoris, rectus femoris and tibialis anterior. Muscle contraction is measures in millivolt using electromyogram with recording electrodes attached to the respective muscles	25 minutes

Collaborators and Investigators

• Sponsor: Balgrist University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): May 14, 2023
• Primary Completion (Estimated): May 31, 2025
• Study Completion (Estimated): May 31, 2025

Study Registration Dates

• First Submitted: September 4, 2023
• First Submitted That Met QC Criteria: December 5, 2023
• First Posted (Estimated): December 14, 2023

Study Record Updates

• Last Update Posted (Estimated): December 14, 2023
• Last Update Submitted That Met QC Criteria: December 5, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Other Study ID Numbers: 2023-00518

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

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