Experimental Pain in Healthy Human Subjects
Conditions
Keywords
pain, tACS, alpha, gamma, neural oscillations, brain
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.
Interventions
DEVICE10 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.
DEVICE10 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.
DEVICE80 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.
DEVICE80 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.
DEVICESham 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.
DEVICESham 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.
Sponsors
German Research Foundation
Technical University of Munich
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
BASIC_SCIENCE
Masking
NONE
Masking description
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.
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).
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Changes in pain rating on visual analogue scale (VAS; 0: 'no pain' to 10: 'maximal tolerable pain') between sessions | 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. | During thermal stimulation, participants will be instructed to continuously rate the currently perceived pain intensity using a finger-span device. |
| Changes in skin conductance responses (µS) between sessions | 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. | Skin conductance responses will be recorded using two electrodes attached to the index and middle finger of the left hand. |
| Changes in heart rate (BPM, beats per minute) between sessions | 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. | The electrocardiogram (ECG) will be recorded using two electrodes placed under the right clavicle and below the sternum, respectively. |
| Changes in oscillatory brain activity before and after tACS application within each session | 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. | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Perception of tACS induced visual and skin sensations measured by numerical rating scale (NRS; 0: 'no sensation' to 10: 'very strong sensation') | 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. | The perception of visual and skin sensations induced by the tACS protocols will be assessed using a custom questionnaire. |
Countries
Germany
Outcome results
None listed