Modulating Pain Using Transcranial Alternating Stimulation (tACS) in Healthy Human Subjects

NCT ID: NCT03805854

Last Updated: 2020-06-04

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

NA

Total Enrollment

39 participants

Study Classification

INTERVENTIONAL

Study Start Date

2019-04-15

Study Completion Date

2019-10-23

Brief Summary

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Pain is a highly complex and subjective phenomenon which results from the dynamic integration of sensory and contextual (i.e. cognitive, emotional, and motivational) processes. Recent evidence suggests that neural oscillations and their synchronization between different brain areas might form the basis of these integrative functions. When investigating tonic experimental pain lasting for several minutes, for example, objective stimulus intensity is inversely related to alpha (8-13 Hz) and beta (13-30 Hz) oscillations in early somatosensory areas, while subjective pain intensity is positively associated with gamma (30-100 Hz) oscillations in prefrontal cortex. Yet, with a few exemptions, reported links between oscillatory brain activity and pain have mostly been established by correlative approaches which do not allow to infer causality. The current project aims at comprehensively investigating the causal role of neural oscillations for tonic experimental pain in healthy human subjects. To this end, transcranial alternating current stimulation (tACS) will be employed to modulate oscillatory brain activity in alpha and gamma frequency bands and investigate effects of this manipulation on pain perception and pain-related autonomic responses. Using an established tonic pain stimulation protocol and a double-blind, sham-controlled design, effects of tACS of somatosensory as well as prefrontal brain areas will be investigated. Results promise to elucidate the neural mechanisms underlying tonic experimental pain by testing the mechanistic role of neural oscillations in different aspects of pain processing. Furthermore, they might contribute to the development of urgently needed new treatment approaches for chronic pain using neuromodulatory methods.

Detailed Description

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Conditions

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Experimental Pain in Healthy Human Subjects

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Each participant will participate in 6 experimental conditions aimed at studying the effect of different tACS protocols on pain processing: (1) 10 Hz tACS of the bilateral somatosensory cortex, (2) 10 Hz tACS of the prefrontal cortex, (3) 80 Hz tACS of the bilateral somatosensory cortex, (4) 80 Hz tACS of the prefrontal cortex, (5) sham stimulation of the bilateral somatosensory cortex, and (6) sham stimulation of the prefrontal cortex. Each condition will be administered in an individual session. Sessions will be conducted in pseudo-randomized order and separated by at least 24 hours to avoid any carry-over effects of the stimulation. During each tACS administration, pain will be induced by means of an established tonic thermal stimulation paradigm lasting for several minutes (TSA-II; Medoc, Ramat Yishai, Israel) while pain ratings and autonomic responses will be recorded (Nickel et al., 2017a; Nickel et al., 2017b).
Primary Study Purpose

BASIC_SCIENCE

Blinding Strategy

NONE

Neither participants nor the conducting investigator will be informed about the administered tACS protocol (10 Hz tACS, 80 Hz tACS or sham stimulation) (= double-blind study). Blinding of participants will be achieved by using tACS intensities which should not evoke perceivable stimulation side effects like skin or visual sensations. Blinding of participants will be controlled using post-hoc questionnaires. An unblinded research assistant who does not interact with the participants will be responsible for initiating and monitoring the appropriate tACS protocol and, thus, enable the blinding of the conducting investigator.

Study Groups

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Transcranial alternating current stimulation (tACS)

Group Type EXPERIMENTAL

10 Hz tACS of the bilateral somatosensory cortex

Intervention Type DEVICE

10 Hz tACS at 1 mA will be applied over the bilateral somatosensory cortex for 10 minutes using a Neuroconn stimulator (DC-Stimulator MR; Neuroconn, Ilmenau, Germany) and 2 5\*5 cm rubber electrodes placed at electrode positions CP3 and CP4 according to the international 10-20 system.

10 Hz tACS of the prefrontal cortex

Intervention Type DEVICE

10 Hz tACS at 1 mA will be applied over the prefrontal cortex for 10 minutes using a Neuroconn stimulator (DC-Stimulator MR; Neuroconn, Ilmenau, Germany) and 2 5\*5 cm rubber electrodes placed at electrode positions F3 and F4 according to the international 10-20 system.

80 Hz tACS of the bilateral somatosensory cortex

Intervention Type DEVICE

80 Hz tACS at 1 mA will be applied over the bilateral somatosensory cortex for 10 minutes using a Neuroconn stimulator (DC-Stimulator MR; Neuroconn, Ilmenau, Germany) and 2 5\*5 cm rubber electrodes placed at electrode positions CP3 and CP4 according to the international 10-20 system.

80 Hz tACS of the prefrontal cortex

Intervention Type DEVICE

80 Hz tACS at 1 mA will be applied over the prefrontal cortex for 10 minutes using a Neuroconn stimulator (DC-Stimulator MR; Neuroconn, Ilmenau, Germany) and 2 5\*5 cm rubber electrodes placed at electrode positions F3 and F4 according to the international 10-20 system.

Sham stimulation of the bilateral somatosensory cortex

Intervention Type DEVICE

10 Hz tACS at 1 mA will be applied over the bilateral somatosensory cortex for 10 seconds at the beginning of the experimental session using a Neuroconn stimulator (DC-Stimulator MR; Neuroconn, Ilmenau, Germany) and 2 5\*5 cm rubber electrodes placed at electrode positions CP3 and CP4 according to the international 10-20 system.

Sham stimulation of the prefrontal cortex

Intervention Type DEVICE

10 Hz tACS at 1 mA will be applied over the prefrontal cortex for 10 seconds at the beginning of the experimental session using a Neuroconn stimulator (DC-Stimulator MR; Neuroconn, Ilmenau, Germany) and 2 5\*5 cm rubber placed at electrode positions F3 and F4 according to the international 10-20 system.

Interventions

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10 Hz tACS of the bilateral somatosensory cortex

10 Hz tACS at 1 mA will be applied over the bilateral somatosensory cortex for 10 minutes using a Neuroconn stimulator (DC-Stimulator MR; Neuroconn, Ilmenau, Germany) and 2 5\*5 cm rubber electrodes placed at electrode positions CP3 and CP4 according to the international 10-20 system.

Intervention Type DEVICE

10 Hz tACS of the prefrontal cortex

10 Hz tACS at 1 mA will be applied over the prefrontal cortex for 10 minutes using a Neuroconn stimulator (DC-Stimulator MR; Neuroconn, Ilmenau, Germany) and 2 5\*5 cm rubber electrodes placed at electrode positions F3 and F4 according to the international 10-20 system.

Intervention Type DEVICE

80 Hz tACS of the bilateral somatosensory cortex

80 Hz tACS at 1 mA will be applied over the bilateral somatosensory cortex for 10 minutes using a Neuroconn stimulator (DC-Stimulator MR; Neuroconn, Ilmenau, Germany) and 2 5\*5 cm rubber electrodes placed at electrode positions CP3 and CP4 according to the international 10-20 system.

Intervention Type DEVICE

80 Hz tACS of the prefrontal cortex

80 Hz tACS at 1 mA will be applied over the prefrontal cortex for 10 minutes using a Neuroconn stimulator (DC-Stimulator MR; Neuroconn, Ilmenau, Germany) and 2 5\*5 cm rubber electrodes placed at electrode positions F3 and F4 according to the international 10-20 system.

Intervention Type DEVICE

Sham stimulation of the bilateral somatosensory cortex

10 Hz tACS at 1 mA will be applied over the bilateral somatosensory cortex for 10 seconds at the beginning of the experimental session using a Neuroconn stimulator (DC-Stimulator MR; Neuroconn, Ilmenau, Germany) and 2 5\*5 cm rubber electrodes placed at electrode positions CP3 and CP4 according to the international 10-20 system.

Intervention Type DEVICE

Sham stimulation of the prefrontal cortex

10 Hz tACS at 1 mA will be applied over the prefrontal cortex for 10 seconds at the beginning of the experimental session using a Neuroconn stimulator (DC-Stimulator MR; Neuroconn, Ilmenau, Germany) and 2 5\*5 cm rubber placed at electrode positions F3 and F4 according to the international 10-20 system.

Intervention Type DEVICE

Eligibility Criteria

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Inclusion Criteria

* aged 18-65 years
* Right-handedness
* Written informed consent

Exclusion Criteria

* Pregnancy
* Neurological or psychiatric diseases (e.g. epilepsy, stroke, depression, anxiety disorders)
* Severe general illnesses (e.g. tumors, diabetes)
* Skin diseases (e.g. dermatitis, psoriasis or eczema)
* Current or recurrent pain
* Regular intake of medication
* Surgical procedures involving the head or spinal cord
* Head trauma followed by impairment of consciousness
* Past fainting spells or syncopes
* Metal (except titanium) or electronic implants
* Side-effects following previous electrical or magnetic stimulation
* Side-effects following previous thermal stimulation
Minimum Eligible Age

18 Years

Maximum Eligible Age

65 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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German Research Foundation

OTHER

Sponsor Role collaborator

Technical University of Munich

OTHER

Sponsor Role lead

Responsible Party

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Markus Ploner

Heisenberg Professor of Human Pain Research

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Markus Ploner, Prof. Dr. med.

Role: PRINCIPAL_INVESTIGATOR

Department of Neurology, Klinikum rechts der Isar, Technische Universität München

Locations

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Department of Neurology, Klinikum rechts der Isar, Technische Universität München

Munich, Bavaria, Germany

Site Status

Countries

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Germany

References

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Ahn S, Prim JH, Alexander ML, McCulloch KL, Frohlich F. Identifying and Engaging Neuronal Oscillations by Transcranial Alternating Current Stimulation in Patients With Chronic Low Back Pain: A Randomized, Crossover, Double-Blind, Sham-Controlled Pilot Study. J Pain. 2019 Mar;20(3):277.e1-277.e11. doi: 10.1016/j.jpain.2018.09.004. Epub 2018 Sep 27.

Reference Type BACKGROUND
PMID: 30268803 (View on PubMed)

Arendsen LJ, Hugh-Jones S, Lloyd DM. Transcranial Alternating Current Stimulation at Alpha Frequency Reduces Pain When the Intensity of Pain is Uncertain. J Pain. 2018 Jul;19(7):807-818. doi: 10.1016/j.jpain.2018.02.014. Epub 2018 Mar 15.

Reference Type BACKGROUND
PMID: 29551661 (View on PubMed)

Herrmann CS, Rach S, Neuling T, Struber D. Transcranial alternating current stimulation: a review of the underlying mechanisms and modulation of cognitive processes. Front Hum Neurosci. 2013 Jun 14;7:279. doi: 10.3389/fnhum.2013.00279. eCollection 2013.

Reference Type BACKGROUND
PMID: 23785325 (View on PubMed)

Jensen MP, Day MA, Miro J. Neuromodulatory treatments for chronic pain: efficacy and mechanisms. Nat Rev Neurol. 2014 Mar;10(3):167-78. doi: 10.1038/nrneurol.2014.12. Epub 2014 Feb 18.

Reference Type BACKGROUND
PMID: 24535464 (View on PubMed)

Nickel MM, May ES, Tiemann L, Postorino M, Ta Dinh S, Ploner M. Autonomic responses to tonic pain are more closely related to stimulus intensity than to pain intensity. Pain. 2017 Nov;158(11):2129-2136. doi: 10.1097/j.pain.0000000000001010.

Reference Type BACKGROUND
PMID: 28700538 (View on PubMed)

Nickel MM, May ES, Tiemann L, Schmidt P, Postorino M, Ta Dinh S, Gross J, Ploner M. Brain oscillations differentially encode noxious stimulus intensity and pain intensity. Neuroimage. 2017 Mar 1;148:141-147. doi: 10.1016/j.neuroimage.2017.01.011. Epub 2017 Jan 7.

Reference Type BACKGROUND
PMID: 28069543 (View on PubMed)

Ploner M, Sorg C, Gross J. Brain Rhythms of Pain. Trends Cogn Sci. 2017 Feb;21(2):100-110. doi: 10.1016/j.tics.2016.12.001. Epub 2016 Dec 23.

Reference Type BACKGROUND
PMID: 28025007 (View on PubMed)

Polania R, Nitsche MA, Ruff CC. Studying and modifying brain function with non-invasive brain stimulation. Nat Neurosci. 2018 Feb;21(2):174-187. doi: 10.1038/s41593-017-0054-4. Epub 2018 Jan 8.

Reference Type BACKGROUND
PMID: 29311747 (View on PubMed)

Schulz E, May ES, Postorino M, Tiemann L, Nickel MM, Witkovsky V, Schmidt P, Gross J, Ploner M. Prefrontal Gamma Oscillations Encode Tonic Pain in Humans. Cereb Cortex. 2015 Nov;25(11):4407-14. doi: 10.1093/cercor/bhv043. Epub 2015 Mar 8.

Reference Type BACKGROUND
PMID: 25754338 (View on PubMed)

Sitaram R, Ros T, Stoeckel L, Haller S, Scharnowski F, Lewis-Peacock J, Weiskopf N, Blefari ML, Rana M, Oblak E, Birbaumer N, Sulzer J. Closed-loop brain training: the science of neurofeedback. Nat Rev Neurosci. 2017 Feb;18(2):86-100. doi: 10.1038/nrn.2016.164. Epub 2016 Dec 22.

Reference Type BACKGROUND
PMID: 28003656 (View on PubMed)

Vosskuhl J, Struber D, Herrmann CS. Non-invasive Brain Stimulation: A Paradigm Shift in Understanding Brain Oscillations. Front Hum Neurosci. 2018 May 25;12:211. doi: 10.3389/fnhum.2018.00211. eCollection 2018.

Reference Type BACKGROUND
PMID: 29887799 (View on PubMed)

May ES, Hohn VD, Nickel MM, Tiemann L, Gil Avila C, Heitmann H, Sauseng P, Ploner M. Modulating Brain Rhythms of Pain Using Transcranial Alternating Current Stimulation (tACS) - A Sham-Controlled Study in Healthy Human Participants. J Pain. 2021 Oct;22(10):1256-1272. doi: 10.1016/j.jpain.2021.03.150. Epub 2021 Jun 12.

Reference Type DERIVED
PMID: 33845173 (View on PubMed)

Other Identifiers

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01/2019

Identifier Type: -

Identifier Source: org_study_id

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