Is Nociceptive Processing Evoked by Heat Homeostatically Regulated: A Contact-heat Evoked Potentials Study

NCT06197529 | Completed

• 1 other identifier: CHEPS-DMZ-CNAP
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

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.

Conditions

Healthy

Keywords

Homeostatic Plasticity; Capsaicin; Transcranial Direct Current Stimulation

Outcome Measures

Primary Outcomes (5)

• 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

Secondary Outcomes (16)

• Pain Intensity After Stimulation Blocks (0-10)

  0 minutes after the first block of CHEP stimulation

• Pain Intensity After Stimulation Blocks (0-10)

  0 minutes after the second block of CHEP stimulation

• Pain Intensity After Stimulation Blocks

  0 minutes after the third block of CHEP stimulation

• Pain Intensity After Stimulation Blocks

  0 minutes after the fourth block of CHEP stimulation

• Pain Intensity After Stimulation Blocks

  0 minutes after the fifth block of CHEP stimulation

Study Arms (4)

S1 Homeostatic Plasticity-Pain

EXPERIMENTAL

Anodal tDCS CP3 1mA FP2 -1mA 4x4 patch on the dorsum of the hand

Other: Homeostatic Plasticity; Drug: Topical alone (Capsaicin 8% Patch)

S1 Homeostatic Plasticity-NoPain

PLACEBO COMPARATOR

Anodal tDCS C3 1mA FP2 -1mA 4x4 patch on the dorsum of the hand

Other: Homeostatic Plasticity; Other: Placebo Patch

S1 Homeostatic Plasticity-Sham

SHAM COMPARATOR

Sham tDCS C3 FP2 4x4 patch on the dorsum of the hand

Other: Placebo Patch; Other: Homeostatic Plasticity (Sham)

M1 Homeostatic Plasticity

ACTIVE COMPARATOR

Anodal tDCS C3 1mA FP2 -1mA 4x4 patch on the dorsum of the hand

Other: Homeostatic Plasticity; Other: Placebo Patch

Interventions

Homeostatic Plasticity OTHER

Anodal tDCS S1/M1

M1 Homeostatic Plasticity; S1 Homeostatic Plasticity-NoPain; S1 Homeostatic Plasticity-Pain

Topical alone (Capsaicin 8% Patch) DRUG

4x4 patch

Also known as: Qutenza Capsaicin (8%)

S1 Homeostatic Plasticity-Pain

Placebo Patch OTHER

4x4 patch

M1 Homeostatic Plasticity; S1 Homeostatic Plasticity-NoPain; S1 Homeostatic Plasticity-Sham

Homeostatic Plasticity (Sham) OTHER

sham Homeostatic Plasticity protocol over S1

S1 Homeostatic Plasticity-Sham

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy right-handed men and women aged 18-60 years
• Speak, read, and understand English or Danish

You may not qualify if:

• 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)

Sponsors & Collaborators

• Aalborg University: lead

Study Sites (1)

Aalborg University / Center for Neuroplasticity and Pain

Gistrup, 9260, Denmark

Location

Related Publications (7)

• 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.

  PMID: 33503491 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.

  PMID: 34251703 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.

  PMID: 37774909 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.

  PMID: 33635391 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.

  PMID: 29472134 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.

  PMID: 36473333 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.

  PMID: 30085357 BACKGROUND

MeSH Terms

Interventions

Single Person; Capsaicin; Transdermal Patch; salicylhydroxamic acid

Intervention Hierarchy (Ancestors)

Marital Status; Family Characteristics; Demography; Population Characteristics; Socioeconomic Factors; Polyunsaturated Alkamides; Amides; Organic Chemicals; Alkenes; Hydrocarbons, Acyclic; Hydrocarbons; Catechols; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Solanaceous Alkaloids; Alkaloids; Heterocyclic Compounds; Fatty Acids, Monounsaturated; Fatty Acids, Unsaturated; Fatty Acids; Lipids; Equipment and Supplies

Study Officials

• Thomas Graven-Nielsen, PhD, DMSc

  Aalborg University

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: November 22, 2023
• First Posted: January 9, 2024
• Study Start: November 21, 2023
• Primary Completion: March 4, 2024
• Study Completion: March 4, 2024
• Last Updated: May 16, 2024

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will not share

Locations

DK (1)