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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.
Randomized, cross-over study of four sessions
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| S1 Homeostatic Plasticity-Pain | Experimental | Anodal tDCS CP3 1mA FP2 -1mA 4x4 patch on the dorsum of the hand |
|
| S1 Homeostatic Plasticity-NoPain | Placebo Comparator | Anodal tDCS C3 1mA FP2 -1mA 4x4 patch on the dorsum of the hand |
|
| S1 Homeostatic Plasticity-Sham | Sham Comparator | Sham tDCS C3 FP2 4x4 patch on the dorsum of the hand |
|
| M1 Homeostatic Plasticity | Active Comparator | Anodal tDCS C3 1mA FP2 -1mA 4x4 patch on the dorsum of the hand |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Homeostatic Plasticity | Other | Anodal tDCS S1/M1 |
|
| Measure | Description | Time Frame |
|---|---|---|
| Contact Heat Evoked Potentials | Baseline (Evoked Potentials after stimulus onset from electroencephalographic channels) | Pre-patch application |
| Contact Heat Evoked Potentials | Post-Patch (Evoked Potentials after stimulus onset from electroencephalographic channels) | 30 minutes after patch application |
| Contact Heat Evoked Potentials | Post-Priming (Evoked Potentials after stimulus onset from electroencephalographic channels) | During the homeostatic plasticity protocol - 0 minutes after the first block of anodal tDCS |
| Contact Heat Evoked Potentials | Post-HP (Evoked Potentials after stimulus onset from electroencephalographic channels) | 0 minutes after homeostatic plasticity induction |
| Contact Heat Evoked Potentials | Post-HP+10 minutes (Evoked Potentials after stimulus onset from electroencephalographic channels) | 10 minutes after the homeostatic plasticity protocol |
| Measure | Description | Time Frame |
|---|---|---|
| Pain Intensity After Stimulation Blocks (0-10) | Pain intensity measured using an 11-point numeric rating scale where 0= no pain and 10 = worst imaginable pain | 0 minutes after the first block of CHEP stimulation |
| Pain Intensity After Stimulation Blocks (0-10) |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Thomas Graven-Nielsen, PhD, DMSc | Aalborg University | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Aalborg University / Center for Neuroplasticity and Pain | Gistrup | 9260 | Denmark |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 33503491 | Background | Wittkopf PG, Larsen DB, Gregoret L, Graven-Nielsen T. Prolonged corticomotor homeostatic plasticity - Effects of different protocols and their reliability. Brain Stimul. 2021 Mar-Apr;14(2):327-329. doi: 10.1016/j.brs.2021.01.017. Epub 2021 Jan 24. No abstract available. | |
| 34251703 | Background | Wittkopf PG, Larsen DB, Graven-Nielsen T. Protocols for inducing homeostatic plasticity reflected in the corticospinal excitability in healthy human participants: A systematic review and meta-analysis. Eur J Neurosci. 2021 Aug;54(4):5444-5461. doi: 10.1111/ejn.15389. Epub 2021 Jul 30. |
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The individual participant data will not be available online, but the data collected can be shared upon reasonable request.
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| ID | Term |
|---|---|
| D012847 | Single Person |
| D002211 | Capsaicin |
| D057968 | Transdermal Patch |
| C005703 | salicylhydroxamic acid |
| ID | Term |
|---|---|
| D017533 | Marital Status |
| D005191 | Family Characteristics |
| D003710 | Demography |
| D011154 | Population Characteristics |
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| Topical alone (Capsaicin 8% Patch) | Drug | 4x4 patch |
|
|
| Placebo Patch | Other | 4x4 patch |
|
| Homeostatic Plasticity (Sham) | Other | sham Homeostatic Plasticity protocol over S1 |
|
Pain intensity measured using an 11-point numeric rating scale where 0= no pain and 10 = worst imaginable pain |
| 0 minutes after the second block of CHEP stimulation |
| Pain Intensity After Stimulation Blocks | Pain intensity measured using an 11-point numeric rating scale where 0= no pain and 10 = worst imaginable pain | 0 minutes after the third block of CHEP stimulation |
| Pain Intensity After Stimulation Blocks | Pain intensity measured using an 11-point numeric rating scale where 0= no pain and 10 = worst imaginable pain | 0 minutes after the fourth block of CHEP stimulation |
| Pain Intensity After Stimulation Blocks | Pain intensity measured using an 11-point numeric rating scale where 0= no pain and 10 = worst imaginable pain | 0 minutes after the fifth block of CHEP stimulation |
| Presence of Allodynia After Stimulation Blocks | Measured with a calibrated brush for the study of dynamic mechanical allodynia (Brush-05®, Somedic SenseLab AB, Sösdala, Sweden) | 0 minutes after the first block of CHEP stimulation |
| Presence of Allodynia After Stimulation Blocks | Measured with a calibrated brush for the study of dynamic mechanical allodynia (Brush-05®, Somedic SenseLab AB, Sösdala, Sweden) | 0 minutes after the second block of CHEP stimulation |
| Presence of Allodynia After Stimulation Blocks | Measured with a calibrated brush for the study of dynamic mechanical allodynia (Brush-05®, Somedic SenseLab AB, Sösdala, Sweden) | 0 minutes after the third block of CHEP stimulation |
| Presence of Allodynia After Stimulation Blocks | Measured with a calibrated brush for the study of dynamic mechanical allodynia (Brush-05®, Somedic SenseLab AB, Sösdala, Sweden) | 0 minutes after the fourth block of CHEP stimulation |
| Presence of Allodynia After Stimulation Blocks | Measured with a calibrated brush for the study of dynamic mechanical allodynia (Brush-05®, Somedic SenseLab AB, Sösdala, Sweden) | 0 minutes after the fifth block of CHEP stimulation |
| Pittsburg Sleeping Quality Index | 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). | Pre-intervention and pre-patch application |
| BECKS Depression Inventory | 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). | Pre-intervention and pre-patch application |
| Positive and Negative Affective Schedule - Short Form | Scores can range from 10 - 50, with higher scores representing higher levels of positive/negative affect. | Pre-intervention and pre-patch application |
| State-Trait Anxiety Inventory | 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. | Pre-intervention and pre-patch application |
| Pain Catastrophizing Scale | 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) | Pre-intervention and pre-patch application |
| Pain intensity (Induced by Capsaicin) | Pain intensity measured using an 11-point numeric rating scale where 0= no pain and 10 = worst imaginable pain | Throughout the experimental session, every 5 minutes and up to 55 minutes after patch application |
| 37774909 | Background | Wittkopf PG, Boye Larsen D, Gregoret L, Graven-Nielsen T. Disrupted Cortical Homeostatic Plasticity Due to Prolonged Capsaicin-induced Pain. Neuroscience. 2023 Nov 21;533:1-9. doi: 10.1016/j.neuroscience.2023.09.011. Epub 2023 Sep 27. |
| 33635391 | Background | Thapa T, Graven-Nielsen T, Schabrun SM. Aberrant plasticity in musculoskeletal pain: a failure of homeostatic control? Exp Brain Res. 2021 Apr;239(4):1317-1326. doi: 10.1007/s00221-021-06062-3. Epub 2021 Feb 26. |
| 29472134 | Background | Thapa T, Graven-Nielsen T, Chipchase LS, Schabrun SM. Disruption of cortical synaptic homeostasis in individuals with chronic low back pain. Clin Neurophysiol. 2018 May;129(5):1090-1096. doi: 10.1016/j.clinph.2018.01.060. Epub 2018 Feb 9. |
| 36473333 | Background | Lejeune N, Petrossova E, Frahm KS, Mouraux A. High-speed heating of the skin using a contact thermode elicits brain responses comparable to CO2 laser-evoked potentials. Clin Neurophysiol. 2023 Feb;146:1-9. doi: 10.1016/j.clinph.2022.11.008. Epub 2022 Nov 24. |
| 30085357 | Background | Lenoir C, Algoet M, Mouraux A. Deep continuous theta burst stimulation of the operculo-insular cortex selectively affects Adelta-fibre heat pain. J Physiol. 2018 Oct;596(19):4767-4787. doi: 10.1113/JP276359. Epub 2018 Sep 4. |
| D012959 |
| Socioeconomic Factors |
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| D006839 | Hydrocarbons, Acyclic |
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| D002396 | Catechols |
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| D006841 | Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
| D012991 | Solanaceous Alkaloids |
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| D005229 | Fatty Acids, Monounsaturated |
| D005231 | Fatty Acids, Unsaturated |
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| D004864 | Equipment and Supplies |