Electrical Intra-cutaneous Half-sine Stimulation for Optimized Preferential C-fiber Activation

NCT05440266 | Completed

• 1 other identifier: 2022-00682; am22Schneider2
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

This exploratory study is to improve an established pain model by a new stimulation profile that allows preferential activation of C fibers that are of main clinical interest in chronic pain and also to generate a stable secondary hyperalgesia, which is of particular interest in the actual research of acute and chronic pain. It is to investigate if the specific activation of afferent sensory fibers and expected lower current intensities makes it more comfortable for the participant as motor neuron activation is much less pronounced at low current intensities. Therefore it compares the area under the curve (AUC) of hyperalgesia during electrical, intracutaneous 25 ms half-sine wave stimulation at a pain level of the numeric rating scale (NRS) of 6 out of 10 for 65 minutes compared to 500 µs rectangular pulses.

Conditions

Pain Perception; Secondary Hyperalgesia

Keywords

C-fiber activation; evoked pain; hyperalgesia; allodynia; half-sine stimulation; 25ms HS stimulation; pain perception; nociceptors; rectangular current stimulation; electrical pain model; numeric rating scale (NRS)

Outcome Measures

Primary Outcomes (1)

• Secondary hyperalgesia measured by the area under the curve (AUCHyperHS)

  Difference between the AUC of secondary hyperalgesia during 25ms half-sine wave stimulation (AUCHyperHS) at pain level NRS 6 for 65 minutes and the AUC of secondary hyperalgesia measured during 500µs rectangular shaped stimulation (AUCHyperRect) at pain level NRS 6 for 65 minutes

  65 minutes from start of stimulation until stop of stimulation

Secondary Outcomes (3)

• Number of pulses needed to reach 25% of the final extent of the flare response

  approx. 65 minutes at each intervention day (first appointment and second appointment)

• Needed time (in minutes) to generate 50% of the final extent of secondary hyperalgesia.

  approx. 65 minutes at each intervention (first appointment and second appointment)

• Current intensity needed to reach same pain level (NRS 6)

  approx. 65 minutes at each intervention day (first appointment and second appointment)

Study Arms (2)

First: half-sine wave stimulation; Second: rectangular shaped stimulation

ACTIVE COMPARATOR

First appointment: Intracutaneously applied electrical 25 ms half-sine wave stimulation with 2 Hz frequency. Second appointment: Intracutaneously applied electrical 500 µs rectangular shaped stimulation with 2 Hz frequency.

Diagnostic Test: Study Intervention: 25 ms half-sine wave stimulation; Diagnostic Test: Control Intervention: 500 µs rectangular shaped stimulation

First: rectangular shaped stimulation; Second: half-sine wave stimulation

ACTIVE COMPARATOR

First appointment: Intracutaneously applied electrical 500 µs rectangular shaped stimulation with 2 Hz frequency. Second appointment: Intracutaneously applied electrical 25 ms half-sine wave stimulation with 2 Hz frequency.

Diagnostic Test: Study Intervention: 25 ms half-sine wave stimulation; Diagnostic Test: Control Intervention: 500 µs rectangular shaped stimulation

Interventions

Study Intervention: 25 ms half-sine wave stimulation DIAGNOSTIC_TEST

Part I: Threshold detection and Flare response: 6 pulses of 25 ms half-sine are given at 2 Hz each, increasing current intensity (mA) until detection threshold, pain threshold and pain level (3 out of 10 NRS) are reached. Determined intensity values reapplied during 214 impulses. Line scan to visualize changes in local skin blood flow done. Part II: Hyperalgesia, Allodynia, Pain and flare response of 65 minutes. Baseline assessment of local skin perfusion and spatial extent of allodynia by using cotton swab and pinprick hyperalgesia. Current intensity is reapplied, adjusted until pain level of 6 reached. After 5 minutes axon reflex flare, allodynia and secondary hyperalgesia are measured and repeated proximal every 10 minutes with last measurement after 65 minutes. In first 15 minutes current intensity is adapted to maintain NRS level of 6. During this 65 minutes' period, 25 ms half-sine is administered continuously.

First: half-sine wave stimulation; Second: rectangular shaped stimulation; First: rectangular shaped stimulation; Second: half-sine wave stimulation

Control Intervention: 500 µs rectangular shaped stimulation DIAGNOSTIC_TEST

Part I: Threshold detection and Flare response: 6 pulses of 500 µs rectangular shaped stimulation are given at 2 Hz each, increasing current intensity (mA) until detection threshold, pain threshold and pain level (3 out of 10 NRS) are reached. Determined intensity values reapplied during 214 impulses. Line scan to visualize changes in local skin blood flow done. Part II: Hyperalgesia, Allodynia, Pain and flare response of 65 minutes. Baseline assessment of local skin perfusion and spatial extent of allodynia by using cotton swab and pinprick hyperalgesia. Current intensity is reapplied, adjusted until pain level of 6 reached. After 5 minutes axon reflex flare, allodynia and secondary hyperalgesia are measured and repeated proximal every 10 minutes with last measurement after 65 minutes. In first 15 minutes current intensity is adapted to maintain NRS level of 6. During this 65 minutes' period, 500 µs rectangular shaped stimulation is administered continuously.

First: half-sine wave stimulation; Second: rectangular shaped stimulation; First: rectangular shaped stimulation; Second: half-sine wave stimulation

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Healthy adults (18 - 65 years old, American Society of Anaesthesiologists (ASA) I or II)
• BMI between 18.5 until 25 kg/m2
• Able to understand the study and the NRS scale
• Able to give informed consent

You may not qualify if:

• Regular intake of medications or drugs potentially interfering with pain sensation (analgesics, opioids, antihistamines, calcium and potassium channel blockers, serotonin / noradrenaline reuptake inhibitors, corticosteroids)
• Neuropathy
• Chronic pain
• Neuromuscular disease
• Dermatological disease as Atopic Dermatitis
• Psychiatric disease
• Pregnancy / Lactation

Sponsors & Collaborators

• University Hospital, Basel, Switzerland: lead

Study Sites (1)

Department of Anaesthesiology, University Hospital of Basel (USB)

Basel, 4031, Switzerland

Location

MeSH Terms

Conditions

Hyperalgesia

Condition Hierarchy (Ancestors)

Somatosensory Disorders; Sensation Disorders; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• Tobias Schneider, Dr. med.

  Department of Anaesthesiology, University Hospital of Basel (USB)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Masking Details: Only the study team will know which stimulation will be applied on which intervention. The participant won't be informed about the applied stimulation type.
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: randomized, crossover, single-blinded experimental proof of concept investigation in healthy volunteers

Study Record Dates

• First Submitted: June 21, 2022
• First Posted: June 30, 2022
• Study Start: May 20, 2022
• Primary Completion: November 25, 2022
• Study Completion: November 25, 2022
• Last Updated: November 28, 2023

Record last verified: 2023-11

Locations

CH (1)