Clinical trial NCT06183593: Accuracy in the Evaluation of Brain Response to Mechanical and Radiofrequency Stimuli in Humans
Official title: Accuracy in the Evaluation of Brain Response to Mechanical and Radiofrequency Stimuli in Humans
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Brain Response Evoked by Radiofrequency Stimuli in Humans
Brain Response Evoked by Pinprick Stimuli in Humans
Lead sponsor: National Council of Scientific and Technical Research, Argentina
Sponsor class: OTHER_GOV
Collaborators: name: Medical School Hamburg
First posted: 2023-12-27
Enrollment: 27
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: BASIC_SCIENCE

Brief summary: Under normal conditions, pain arises as a consequence of the activation of nociceptive afferents (small fibers) by an external stimulus with sufficient intensity to potentially cause tissue damage. This peripheral activation is processed as perception of pain by the central nervous system. In order to reliably evaluate the state of the nociceptive system in both clinical and experimental settings, standardized tests are essential. Quantitative sensory testing (QST) is a set of tests used to measure the intensity of a stimulus that produces a specific sensory perception in a subject. For example, if we gradually apply pressure, the point where the sensation changes from pressure to pain is called the pressure pain threshold. This type of test can be performed with different types of stimuli, including hot and cold stimuli or mechanical stimuli. Although these tests have been shown as reliable in healthy volunteers and pain patients, they are subjective in their nature, since they are based on a conscious evaluation of tested subjects. Likewise, these measures show substantial variability due to differences in the application of the tests by individual examinators. In short, even though the method is quantitative, its methodological characteristics make it subjective and dependent on both the operator and the subject under study. Moreover, contrasting results have been recently found regarding the measurement variability when repeating the QST at intervals of days. Thus, it is essential to investigate and develop new QST alternatives to obtain objective markers that may potentially contribute to the understanding of the mechanisms behind chronic pain conditions.

Detailed description: Under normal conditions, pain arises as a consequence of the activation of nociceptive afferents (small fibers) by an external stimulus with sufficient intensity to potentially cause tissue damage. This peripheral activation is processed as perception of pain by the central nervous system. In order to reliably evaluate the state of the nociceptive system in both clinical and experimental settings, standardized tests are essential. Quantitative sensory testing (QST) is a set of tests used to measure the intensity of a stimulus that produces a specific sensory perception in a subject. For example, if we gradually apply pressure, the point where the sensation changes from pressure to pain is called the pressure pain threshold. This type of test can be performed with different types of stimuli, including hot and cold stimuli or mechanical stimuli. Although these tests have been shown as reliable in healthy volunteers and pain patients, they are subjective in their nature, since they are based on a conscious evaluation of tested subjects. Likewise, these measures show substantial variability due to differences in the application of the tests by individual examinators. In short, even though the method is quantitative, its methodological characteristics make it subjective and dependent on both the operator and the subject under study. Moreover, contrasting results have been recently found regarding the measurement variability when repeating the QST at intervals of days. Thus, it is essential to investigate and develop new QST alternatives to obtain objective markers that may potentially contribute to the understanding of the mechanisms behind chronic pain conditions.

In this regard, evoked potentials (EP) measured by electroencephalography (EEG) are the most commonly used objective alternative for the functional evaluation of small fibers and the spinothalamic tract. Nociceptive EPs can be induced with various stimulation modalities, including lasers (LEP), contact heat (CHEP) and cold (CCEP), intradermal electrical stimulation (IEEP), and mechanical needling (PEP), and each modality has its own advantages and disadvantages. Recently, a novel type of EP has been proposed that is evoked by electrical stimulation in the range of 200 kHz to 3.3 MHz, that is, in the radio frequency (RF) spectrum. At such high frequencies, the nerves and muscles can no longer be electrically excited, and the physiological effects are generated exclusively due to the heating of the tissue. In strictly physiological terms, RF electrical stimuli are similar to those generated by contact heat. Importantly, non-ablative RF technology is safe, relatively inexpensive, and in widespread use in clinics (Beasley \& Weiss, 2014; Lolis \& Goldberg, 2012)- Therefore, the use of RF stimulation could significantly increase the accessibility of EPs as a reference electrophysiological tool for the evaluation of the state of the nociceptive system.

Another attractive alternative to subjective evaluation is the EP elicited by sharp mechanical stimuli (pinprick). A device that applies this type of stimulus has recently been developed. It uses a stimulator with a tip similar to that of a blunt needle, which allows obtaining brain responses synchronized with the stimulus and evaluating the state of the spino-thalamic-cortical mechanical sensory conduction pathways. At the Faculty of Engineering of the National University of Entre Ríos (FI-UNER), a prototype was developed that allows it to be carried out in an automated manner, which allows to reduce the uncertainty derived from human subjectivity.

In the proposed protocol, the precision of the brain response to RF and mechanical sharp stimuli will be evaluated in two experimental settings. We plan to assess the effect of stimulation intensity on signal parameters, such as EP latency and amplitude. Furthermore, the relationship of these parameters with psychophysical results (questionnaires) and heat thresholds will be explored to investigate the relationship between these variables.

Eligibility criteria: Inclusion Criteria:

* ● Age between 18 and 60 years.

  * Willingness and ability to fully understand the content and scope of the experiment and comply with its instructions.
  * Have signed the informed consent.

Exclusion Criteria:

* ● Pregnancy.

  * Ongoing chronic pain or neuromuscular disorder, or any Desis that effect the nociceptive system and not allowed to be evaluated in normal Condition
  * History of addictive behavior, defined as abuse of alcohol, cannabis, opioids, or other drugs.
  * History of heat sensitivity disorders.
  * History of mental illness.
  * Presence of fever, tuberculosis, malignant tumors, infectious processes, acute inflammatory processes
  * Implantation of pacemakers or metal prostheses.
  * Use of analgesics within 24 hours prior to participation in the experiment.
  * Lack of sleep (\< 6 hours) the night before the experiment.
  * High alcohol intake the evening before the experiment.

Primary outcomes:
measure: Latency and amplitude of the evoked potentials induce by pinprick stimuli
timeFrame: 2 hours during each experimental setting
measure: Latency and amplitude of the evoked potentials induce by RF
timeFrame: 2 hours during each experimental setting
Secondary outcomes:
measure: Changes in responses to somatosensory stimuli with Pinprick thresholds
timeFrame: after each pinprick stimulation
measure: Conduction velocity in radiofrequency stimuli
timeFrame: 10 minutes at the end of the RF setting
Other outcomes:
Locations:
city: Oro Verde
country: Argentina
facility: Facutlad de ingenieria UNER
state: Entre Ríos
Study officials:
References:
citation: Iannetti GD, Baumgartner U, Tracey I, Treede RD, Magerl W. Pinprick-evoked brain potentials: a novel tool to assess central sensitization of nociceptive pathways in humans. J Neurophysiol. 2013 Sep;110(5):1107-16. doi: 10.1152/jn.00774.2012. Epub 2013 May 15.
citation: Backonja MM, Walk D, Edwards RR, Sehgal N, Moeller-Bertram T, Wasan A, Irving G, Argoff C, Wallace M. Quantitative sensory testing in measurement of neuropathic pain phenomena and other sensory abnormalities. Clin J Pain. 2009 Sep;25(7):641-7. doi: 10.1097/AJP.0b013e3181a68c7e.
citation: van den Broeke EN, Lambert J, Huang G, Mouraux A. Central Sensitization of Mechanical Nociceptive Pathways Is Associated with a Long-Lasting Increase of Pinprick-Evoked Brain Potentials. Front Hum Neurosci. 2016 Oct 20;10:531. doi: 10.3389/fnhum.2016.00531. eCollection 2016.
citation: Vuilleumier PH, Biurrun Manresa JA, Ghamri Y, Mlekusch S, Siegenthaler A, Arendt-Nielsen L, Curatolo M. Reliability of Quantitative Sensory Tests in a Low Back Pain Population. Reg Anesth Pain Med. 2015 Nov-Dec;40(6):665-73. doi: 10.1097/AAP.0000000000000289.