Healthy
Conditions
Keywords
Homeostatic Plasticity, Capsaicin, Transcranial Direct Current Stimulation
Brief summary
Homeostatic plasticity is a mechanism that stabilizes neuronal activity to prevent excessive nervous system excitability. This mechanism can be investigated in humans by applying two blocks of non-invasive brain stimulation, such as transcranial direct current stimulation (tDCS). In healthy subjects, homeostatic plasticity induction over the primary motor cortex increases the amplitude of motor-evoked potentials after the first block of excitatory tDCS, which then decreases after the second block of excitatory tDCS. However, this mechanism is impaired in chronic and experimental pain, demonstrated by an increase in excitability instead of a reversal. The role of homeostatic plasticity mechanisms in pain is yet to be unraveled, but homeostatic plasticity may hold an important role in pain development or persistence. Thus, the aim of this study is to investigate if the cortical nociceptive response reflected by contact heat stimulation (CHEPs) is regulated by homeostatic mechanisms. For this, homeostatic plasticity will be induced in both the primary motor (M1) and sensory cortices (S1). The first research question will explore if the contact heat evoked potentials are homeostatically regulated and if this regulation is occurring locally or globally in the cortex. Additionally, it will be investigated if and how capsaicin-induced nociception interacts and effects the homeostatic response as reflected by CHEPs.
Detailed description
Randomized, cross-over study of four sessions
Interventions
OTHERHomeostatic Plasticity
Anodal tDCS S1/M1
DRUGTopical alone (Capsaicin 8% Patch)
4x4 patch
OTHERPlacebo Patch
4x4 patch
OTHERHomeostatic Plasticity (Sham)
sham Homeostatic Plasticity protocol over S1
Sponsors
Aalborg University
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
Yes
Inclusion criteria
* Healthy right-handed men and women aged 18-60 years * Speak, read, and understand English or Danish
Exclusion criteria
* Pregnant, breastfeeding, or women in childbearing age not using contraceptive methods * Regular use of cannabis, opioids or other drugs (except contraceptives) * Current or previous neurologic, musculoskeletal, mental, or other illnesses (e.g. brain or spinal cord injuries, degenerative neurological disorders, epilepsy, major depression, cardiovascular disease, chronic lung disease, etc.) * Current or previous chronic or recurrent pain condition (other than low back pain in patients recruited for sub-project 6, and this item does not apply to sub-project 8) * Current regular use of analgesic medication or other medication which may affect the trial (including paracetamol and NSAIDs) For subproject 8, chronic low back pain patients may take analgesic medication provided the dosage is stable * Open wounds, eczema, scars, or tattoos in the area of the heat stimulation (sub-project 1) * Lack of ability to cooperate * Recent history of acute pain particularly in the lower limbs (unless related to low back pain in patients included in sub-project 6 or 8) * Abnormally disrupted sleep in 24 hours preceding experiment * Any medical or other condition (i.e. musculoskeletal, cardiorespiratory, neurological, etc.) * Contraindications to TMS application (history of epilepsy, metal implants in head or jaw, etc.) * Unable to answer to the Transcranial Magnetic Stimulation Adult Safety Screen or tDCS screening questionnaire (see Bilag\_v1\_06092021)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Contact Heat Evoked Potentials | Pre-patch application | Baseline (Evoked Potentials after stimulus onset from electroencephalographic channels) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pain Intensity After Stimulation Blocks (0-10) | 0 minutes after the first block of CHEP stimulation | Pain intensity measured using an 11-point numeric rating scale where 0= no pain and 10 = worst imaginable pain |
| Pain Intensity After Stimulation Blocks | 0 minutes after the third block of CHEP stimulation | Pain intensity measured using an 11-point numeric rating scale where 0= no pain and 10 = worst imaginable pain |
| Presence of Allodynia After Stimulation Blocks | 0 minutes after the first block of CHEP stimulation | Measured with a calibrated brush for the study of dynamic mechanical allodynia (Brush-05®, Somedic SenseLab AB, Sösdala, Sweden) |
| BECKS Depression Inventory | Pre-intervention and pre-patch application | The questionnaire includes 21 items which are rated on a 4-point scale (0 to 3). The total score is calculated by adding all items. Total score values from 0-13 indicate normal ups and downs, and scores between 14-19, 20-28, and 29-63, are interpreted as mild, moderate, and severe symptoms (Beck et al., 1996; Goldstein et al., 2013; Wang and Gorenstein, 2013). |
| Positive and Negative Affective Schedule - Short Form | Pre-intervention and pre-patch application | Scores can range from 10 - 50, with higher scores representing higher levels of positive/negative affect. |
| State-Trait Anxiety Inventory | Pre-intervention and pre-patch application | A 40-item questionnaire that assesses state and trait anxiety with 20 items each (Skapinakis, 2014; Spielberger et al., 1983). Each subscale (S-Anxiety and T-Anxiety) uses a 4-point Linkert scale ranging from 1 (not at all for S- or almost never for T-Anxiety) to 4 (very much so for S- and almost always for T-Anxiety). A higher scole indicates more severe anxiety with a range from 20-80. |
| Pain Catastrophizing Scale | Pre-intervention and pre-patch application | This questionnaire assesses 13 items describing different thoughts and feelings which may be associated with pain. They are rated on a 5-point scale (0-5) indicating the degree to which these thoughts and feelings are present when having pain. The total score is 0-52, with a higher score indicating a higher pain catastrophizing. (Sullivan M J L, Bishop S, Pivik J. 1995) |
| Pain intensity (Induced by Capsaicin) | Throughout the experimental session, every 5 minutes and up to 55 minutes after patch application | Pain intensity measured using an 11-point numeric rating scale where 0= no pain and 10 = worst imaginable pain |
| Pittsburg Sleeping Quality Index | Pre-intervention and pre-patch application | The global PSQI score ranges from 0 to 21, calculated by adding seven component scores. A global score above 5 (PSQI \> 5) indicates relevant sleep disturbances or poor sleep quality (Buysse et al., 1989). |
Countries
Denmark
Outcome results
None listed