Non-invasive Modulation of Spinal Cord Nociceptive Reflexes

Non-invasive Investigation of Excitability Changes in the Human Spinal Cord: the Effect of Transcutaneous Spinal Direct Current Stimulation (tsDCS) on Nociceptive Flexion Reflexes

The aims of this study are threefold. First, to investigate whether spinal nociceptive processing - represented here by the nociceptive flexion reflex (NFR) - is influenced by thoracic transcutaneous spinal direct current stimulation (tsDCS) in a spatially selective manner, i.e., whether effects are only observed for lower limb NFRs, but not for upper limb NFRs. Second, to investigate - in a double-blind, sham-controlled, within-participant design - whether anodal and cathodal tsDCS do affect the NFR in a polarity-dependent manner. Third, to investigate whether tsDCS effects observed on a spinal measure (NFR) are also observed in responses that are mediated supra-spinally, namely autonomic parameters and pain intensity ratings.

Study Overview

• Status: Enrolling by invitation
• Conditions: Pain
• Intervention / Treatment: Other: Transcutaneous spinal direct current stimulation (tsDCS)

• Study Type: Interventional
• Enrollment (Anticipated): 40
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Germany
  • Leipzig, Germany
    • Max Planck Research Group Pain Perception

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 40 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Healthy volunteers between the ages of 18 and 40 years
2. Having participated in the MRI medical assessment session and consented to taking part in 3T MRI measurements in written form
3. Having participated in the magnetic/electric neurostimulation medical assessment session and consented to taking part in magnetic/electric neurostimulation experiments in written form
4. Voluntary participation and signing of the study-specific consent form

Exclusion Criteria:

1. Existence of any contraindications for MRI measurements and magnetic/electric neurostimulation experiments
2. Pregnancy or breastfeeding
3. Very dry or sensitive skin (e.g., intolerance to creams/shampoos)
4. Chronic skin diseases - such as eczema or neurodermatitis - in the area of somatosensory / nociceptive stimulation (arm or hand, leg or foot) or electrophysiological data recording (upper body, arm, leg)
5. Scar tissue in the area of somatosensory / nociceptive stimulation (arm or hand, leg or foot) or electrophysiological data recording (upper body, arm, leg)
6. Acute sunburn in the area of somatosensory / nociceptive stimulation (arm or hand, leg or foot) or electrophysiological data recording (upper body, arm, leg)
7. Current or recurring pain
8. Injuries to the nervous system
9. History of or current neurological or psychiatric disorders
10. Chronic diseases that require permanent medication (e.g., asthma, diabetes mellitus, etc.)
11. Persons not capable of giving consent (e.g., in case of dementia)
12. Lack of consent with regards to report of incidental findings

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Anodal thoracic tsDCS; Anodal tsDCS will be applied over the T12 vertebra	Other: Transcutaneous spinal direct current stimulation (tsDCS); tsDCS will be carried out using a direct current stimulator (DC-Stimulator Plus, neuroConn, Ilmenau, Germany), with one electrode placed above the thoracic spinal cord and the other electrode placed on the right shoulder. We will employ rectangular electrodes of 7 x 5 cm size (neuroConn, Ilmenau, Germany) covered by electrode paste (Ten20 Conductive Paste, Weaver and Company, Aurora, USA). Stimulation will consist of the following phases: a fade-in period of 15 seconds, a plateau period of 20 minutes (with stimulation at 2.5mA either anodally or cathodally) and a fade-out period of 15 seconds. Sham stimulation will follow the anodal montage with 15-second fade-in and fade-out periods, but only 45 seconds of plateau stimulation at 2.5 mA. Such a combination of stimulation and electrodes results in a current density of 0.071mA/cm2, well below thermal and histological limits for current density.
Experimental: Cathodal thoracic tsDCS; Cathodal tsDCS will be applied over the T12 vertebra	Other: Transcutaneous spinal direct current stimulation (tsDCS); tsDCS will be carried out using a direct current stimulator (DC-Stimulator Plus, neuroConn, Ilmenau, Germany), with one electrode placed above the thoracic spinal cord and the other electrode placed on the right shoulder. We will employ rectangular electrodes of 7 x 5 cm size (neuroConn, Ilmenau, Germany) covered by electrode paste (Ten20 Conductive Paste, Weaver and Company, Aurora, USA). Stimulation will consist of the following phases: a fade-in period of 15 seconds, a plateau period of 20 minutes (with stimulation at 2.5mA either anodally or cathodally) and a fade-out period of 15 seconds. Sham stimulation will follow the anodal montage with 15-second fade-in and fade-out periods, but only 45 seconds of plateau stimulation at 2.5 mA. Such a combination of stimulation and electrodes results in a current density of 0.071mA/cm2, well below thermal and histological limits for current density.
Sham Comparator: Sham thoracic tsDCS; Sham tsDCS will be applied over the T12 vertebra	Other: Transcutaneous spinal direct current stimulation (tsDCS); tsDCS will be carried out using a direct current stimulator (DC-Stimulator Plus, neuroConn, Ilmenau, Germany), with one electrode placed above the thoracic spinal cord and the other electrode placed on the right shoulder. We will employ rectangular electrodes of 7 x 5 cm size (neuroConn, Ilmenau, Germany) covered by electrode paste (Ten20 Conductive Paste, Weaver and Company, Aurora, USA). Stimulation will consist of the following phases: a fade-in period of 15 seconds, a plateau period of 20 minutes (with stimulation at 2.5mA either anodally or cathodally) and a fade-out period of 15 seconds. Sham stimulation will follow the anodal montage with 15-second fade-in and fade-out periods, but only 45 seconds of plateau stimulation at 2.5 mA. Such a combination of stimulation and electrodes results in a current density of 0.071mA/cm2, well below thermal and histological limits for current density.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in NFR amplitude	90-150ms for lower limb, 60-200ms for upper limb	Baseline and immediately after the intervention
Change in pain intensity rating	One rating per trial on a standard visual analogue scale (VAS); internally numbered from 0 (no sensation) to 100 (unbearable pain)	Baseline and immediately after the intervention
Change in skin conductance response	Amplitude maximum before onset of pain rating	Baseline and immediately after the intervention
Change in heart period acceleration	Amplitude maximum before onset of pain rating	Baseline and immediately after the intervention

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in NFR area	90-150ms for lower limb, 60-200ms for upper limb	Baseline and immediately after the intervention

Collaborators and Investigators

• Sponsor: Max Planck Research Group Pain Perception

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2022
• Primary Completion (Anticipated): December 31, 2023
• Study Completion (Anticipated): December 31, 2023

Study Registration Dates

• First Submitted: December 10, 2022
• First Submitted That Met QC Criteria: January 31, 2023
• First Posted (Actual): February 3, 2023

Study Record Updates

• Last Update Posted (Actual): March 16, 2023
• Last Update Submitted That Met QC Criteria: March 14, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Other Study ID Numbers: PP016

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: No