Cerebral and Autonomic Responses to Pain in Healthy Humans (ALGOBLOC-1)

Study of Cortical Cerebral Response and Neurovegetative Response to a Nociceptive Stimulus Among Healthy Volunteers

Evaluating the intraoperative pain is a major challenge for the anesthesia team. During anesthesia, changes in heart rate and blood pressure are interpreted qualitatively to evaluate the sympathetic response to nociceptive stimulation or the adaptation of analgesia during surgery. The new nociception monitors under development quantitatively explore other variables dependent on sympathetic activity or sympathetic / parasympathetic balance, such as the pulse wave amplitude measurement (Surgical Pleth Index (SPI index)), the pupil dilation reflex, respiratory sinus arrhythmia (ANI, Analgesia Nociception Index), or skin conductance index. Taken independently, these tools provide an assessment of nociception based on variations in the autonomic system, more robust than simply observing heart rate or blood pressure raw values.

However, the relationship between variations in the neurovegetative system and pain can be compromised by various factors or intraoperative events such as hypovolemia, bleeding, certain sympathomimetic or sympatholytic treatments, the hypnosis depth, ventilation variation, fast filling, or body temperature. Moreover, investigators do not know the delay between the application of the painful stimulus and the observation of the variation of the different neurovegetative variables. This constitutes a limit of the practitioners' confidence in these monitoring tools.

The nociception transmission pathways of to the vegetative centers and cortical areas are complex. Investigators hypothesis is that neurovegetative variations in response to nociceptive stimulation are not always associated with a cortical somatosensory response. In this project investigators investigate the relation between cortical (EEG) and vegetative reactions to acute and tonic nociceptive stimuli, as a preliminary step to apply these procedures to assess intraoperative reactions to nociceptive procedures in anesthetized patients.

Study Overview

• Status: Completed
• Conditions: Healthy; Anesthesia; Nociceptive Pain
• Intervention / Treatment: Other: Nociceptive stimulation

• Study Type: Interventional
• Enrollment (Actual): 21
• Phase: Not Applicable

Contacts and Locations

Study Locations

• France
  • Bron, France, 69677
    • Service de Neurologie Fonctionnelle et Epileptologie Hôpital Neurologique, GHE Hospices civils de Lyon

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Healthy volunteer over 18 years old
• signed informed consent
• affiliated to a social security

Exclusion Criteria:

• Chronic pathology requiring chronic treatment
• Cardiac rhythm disorders, pacemaker, cardiotropic treatment
• Taking opioid analgesics during the previous week
• Painful chronic, or migraine
• Pathology of the hand, acrosyndrome, carpal tunnel syndrome
• Pregnancy
• People placed under protection of justice

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: Experimental; Nociceptive intervention arm

Other: Nociceptive stimulation; These investigations in healthy volunteers will study the association between cerebral and neurovegetative (sympathetic and parasympathetic) electrophysiological responses in response to a controlled and tolerable pain stimulus, determined for each individual. The pain stimulus will be delivered using an electrically conductive glove used in clinical practice for transcutaneous therapeutic stimulation. The thresholds of nociception and tolerance will be determined in each healthy volunteer.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Simultaneous scheme of cortical activation and neuro-vegetative responses to controlled nociceptive stimuli	Simultaneous scheme of cortical activation and neuro-vegetative responses secondary to controlled nociceptive stimuli will be defined as the occurrence of at least one among the following: Changes of time-frequency distribution of the electroencephalographic activity during phasic or tonic pain stimulation, compared to a prior baseline period.; Recording of cortical evoked responses during phasic pain stimulation in a time latency range between 100-500 msec.; Changes in parasympathetic tone measured by Analgesia/Nociception Index (ANI) method (threshold of 50/100) during phasic or tonic stimulation; Recording of the skin conductance reflex (skin sympathetic response) during phasic or tonic stimulations	Day 1

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
EEG time-frequency analysis during phasic pain stimulation	Analysis of time-frequency maps to compare the amplitude in each frequency band during phasic stimulation condition and prior baseline period	Day 1
Latency of evoked responses to phasic stimulation	Measure of mean latency of evoked responses to phasic stimulation in a time range of 100-500 msec	Day 1
Pick-to-pick amplitude of evoked responses to phasic stimulation	Measure of mean pick-to-pick amplitude of evoked responses to phasic stimulation in a time range of 100-500 msec	Day 1
Quantification of skin sympathetic response during phasic stimulation	Mean area under the curve of skin sympathetic response during phasic stimulation compared to the baseline periods before stimulation	Day 1
Qualitative Change of ANI Value during phasic stimulation	Mean percentage of decrease of ANI value during phasic stimulation compared with the baseline period before stimulation	Day 1
EEG time-frequency analysis during tonic pain stimulation	Analysis of time-frequency maps to compare the amplitude in each frequency band during tonic stimulation condition and prior baseline period	Day 1
Quantification of skin sympathetic response during tonic stimulation	Mean area under the curve of skin sympathetic response during tonic stimulation compared to the baseline period before stimulation	Day 1
Qualitative Change of ANI Value during tonic stimulation	Mean percentage of decrease of ANI value during tonic stimulation compared with the baseline period before stimulation	Day 1
Selection of dominant configuration of pattern in terms of sensitivity / specificity of the response to different types of nociceptive stimulation	Among the EEG and neurovegetative modifications, investigators will select the dominant association according to the different types of nociceptive stimulation. The dominant association will constitute the pattern of interest. This pattern will be selected if present in more than 80% of subjects. If investigators obtain several patterns of interest associating different cortical or neurovegetative parameters, the final selected pattern will be made up of the smallest number of parameters in order to envisage its transfer in anesthesiological routine	Day 1

Collaborators and Investigators

• Sponsor: Hospices Civils de Lyon

Study record dates

Study Major Dates

• Study Start (Actual): April 6, 2021
• Primary Completion (Actual): July 8, 2021
• Study Completion (Actual): July 8, 2021

Study Registration Dates

• First Submitted: January 22, 2020
• First Submitted That Met QC Criteria: June 7, 2021
• First Posted (Actual): June 14, 2021

Study Record Updates

• Last Update Posted (Actual): October 15, 2021
• Last Update Submitted That Met QC Criteria: October 14, 2021
• Last Verified: October 1, 2021

More Information

Terms related to this study

• Keywords: Healthy volunteer; Nociceptive stimulation; Simultaneous cortical activation; Neuro-vegetative response
• Additional Relevant MeSH Terms: Pain; Neurologic Manifestations; Nociceptive Pain
• Other Study ID Numbers: 69HCL19_0669

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