Clinical trial NCT03805854: Modulating Pain Using Transcranial Alternating Stimulation (tACS) in Healthy Human Subjects
Official title: Modulating Pain Using Transcranial Alternating Stimulation (tACS) in Healthy Human Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Experimental Pain in Healthy Human Subjects
Keywords: pain
tACS
alpha
gamma
neural oscillations
brain
Lead sponsor: Technical University of Munich
Sponsor class: OTHER
Collaborators: name: German Research Foundation
First posted: 2019-01-16
Enrollment: 39
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: 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 purpose: BASIC_SCIENCE

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: Changes in pain rating on visual analogue scale (VAS; 0: 'no pain' to 10: 'maximal tolerable pain') between sessions
timeFrame: During 10 min thermal stimulation in each of six interventions (10 Hz tACS/80 Hz tACS/sham stimulation of the somatosensory/prefrontal cortex), which are separated by at least 24 hrs.
measure: Changes in skin conductance responses (µS) between sessions
timeFrame: During 10 min thermal stimulation in each of six interventions (10 Hz tACS/80 Hz tACS/sham stimulation of the somatosensory/prefrontal cortex), which are separated by at least 24 hrs.
measure: Changes in heart rate (BPM, beats per minute) between sessions
timeFrame: During 10 min thermal stimulation in each of six interventions (10 Hz tACS/80 Hz tACS/sham stimulation of the somatosensory/prefrontal cortex), which are separated by at least 24 hrs.
measure: Changes in oscillatory brain activity before and after tACS application within each session
timeFrame: Measured immediately before and after the tACS protocol in each of six interventions (10 Hz tACS/80 Hz tACS/sham stimulation of the somatosensory/prefrontal cortex), which are separated by at least 24 hrs.
Secondary outcomes:
measure: Perception of tACS induced visual and skin sensations measured by numerical rating scale (NRS; 0: 'no sensation' to 10: 'very strong sensation')
timeFrame: Measured immediately after the EEG measurement following each of six interventions (10 Hz tACS/80 Hz tACS/sham stimulation of the somatosensory/prefrontal cortex), which are separated by at least 24 hrs.
Other outcomes:
Locations:
city: Munich
country: Germany
facility: Department of Neurology, Klinikum rechts der Isar, Technische Universität München
state: Bavaria
Study officials:
affiliation: Department of Neurology, Klinikum rechts der Isar, Technische Universität München
name: Markus Ploner, Prof. Dr. med.
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.