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

Experimental Pain in Healthy Human Subjects Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03805854
• Other study ID #: 01/2019
• Status: Completed
• Phase: N/A
• Start date: April 15, 2019
• Est. completion date: October 23, 2019

Study information

• Verified date: June 2020
• Source: Technische Universität München
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 39
• Est. completion date: October 23, 2019
• Est. primary completion date: October 23, 2019
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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

Related Conditions & MeSH terms

• Experimental Pain in Healthy Human Subjects

Intervention

Device:
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.

Locations

Country	Name	City	State
Germany	Department of Neurology, Klinikum rechts der Isar, Technische Universität München	Munich	Bavaria

Sponsors (2)

Lead Sponsor	Collaborator
Technische Universität München	German Research Foundation

Country where clinical trial is conducted

Germany, 

References & Publications (11)

Ahn S, Prim JH, Alexander ML, McCulloch KL, Fröhlich 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. — View 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. — View Citation

Herrmann CS, Rach S, Neuling T, Strüber 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. — View Citation

Jensen MP, Day MA, Miró 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. Review. — View 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. — View 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. — View 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. Review. — View Citation

Polanía 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. Review. — View 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. — View 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. Review. Erratum in: Nat Rev Neurosci. 2019 May;20(5):314. — View Citation

Vosskuhl J, Strüber 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. Review. — View Citation

* Note: There are 11 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Changes in pain rating on visual analogue scale (VAS; 0: 'no pain' to 10: 'maximal tolerable pain') between sessions	During thermal stimulation, participants will be instructed to continuously rate the currently perceived pain intensity using a finger-span device.	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.
Primary	Changes in skin conductance responses (µS) between sessions	Skin conductance responses will be recorded using two electrodes attached to the index and middle finger of the left hand.	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.
Primary	Changes in heart rate (BPM, beats per minute) between sessions	The electrocardiogram (ECG) will be recorded using two electrodes placed under the right clavicle and below the sternum, respectively.	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.
Primary	Changes in oscillatory brain activity before and after tACS application within each session	5-minute resting state electroencephalogram (EEG) will be recorded with two electrodes placed at the same electrode positions used for the respective tACS protocol. Power of oscillatory brain activity will be quantified in the alpha (8-12 Hz) and gamma (30-100 Hz) bands.	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	Perception of tACS induced visual and skin sensations measured by numerical rating scale (NRS; 0: 'no sensation' to 10: 'very strong sensation')	The perception of visual and skin sensations induced by the tACS protocols will be assessed using a custom questionnaire.	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.