Clinical trial NCT06197529: Is Nociceptive Processing Evoked by Heat Homeostatically Regulated: A Contact-heat Evoked Potentials Study
Official title: Is Nociceptive Processing Evoked by Heat Homeostatically Regulated: A Contact-heat Evoked Potentials Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Healthy
Keywords: Homeostatic Plasticity
Capsaicin
Transcranial Direct Current Stimulation
Lead sponsor: Aalborg University
Sponsor class: OTHER
First posted: 2024-01-09
Enrollment: 18
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

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

Eligibility criteria: 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)

Primary outcomes:
measure: Contact Heat Evoked Potentials
timeFrame: Pre-patch application
measure: Contact Heat Evoked Potentials
timeFrame: 30 minutes after patch application
measure: Contact Heat Evoked Potentials
timeFrame: During the homeostatic plasticity protocol - 0 minutes after the first block of anodal tDCS
measure: Contact Heat Evoked Potentials
timeFrame: 0 minutes after homeostatic plasticity induction
measure: Contact Heat Evoked Potentials
timeFrame: 10 minutes after the homeostatic plasticity protocol
Secondary outcomes:
measure: Pain Intensity After Stimulation Blocks (0-10)
timeFrame: 0 minutes after the first block of CHEP stimulation
measure: Pain Intensity After Stimulation Blocks (0-10)
timeFrame: 0 minutes after the second block of CHEP stimulation
measure: Pain Intensity After Stimulation Blocks
timeFrame: 0 minutes after the third block of CHEP stimulation
measure: Pain Intensity After Stimulation Blocks
timeFrame: 0 minutes after the fourth block of CHEP stimulation
measure: Pain Intensity After Stimulation Blocks
timeFrame: 0 minutes after the fifth block of CHEP stimulation
measure: Presence of Allodynia After Stimulation Blocks
timeFrame: 0 minutes after the first block of CHEP stimulation
measure: Presence of Allodynia After Stimulation Blocks
timeFrame: 0 minutes after the second block of CHEP stimulation
measure: Presence of Allodynia After Stimulation Blocks
timeFrame: 0 minutes after the third block of CHEP stimulation
measure: Presence of Allodynia After Stimulation Blocks
timeFrame: 0 minutes after the fourth block of CHEP stimulation
measure: Presence of Allodynia After Stimulation Blocks
timeFrame: 0 minutes after the fifth block of CHEP stimulation
measure: Pittsburg Sleeping Quality Index
timeFrame: Pre-intervention and pre-patch application
measure: BECKS Depression Inventory
timeFrame: Pre-intervention and pre-patch application
measure: Positive and Negative Affective Schedule - Short Form
timeFrame: Pre-intervention and pre-patch application
measure: State-Trait Anxiety Inventory
timeFrame: Pre-intervention and pre-patch application
measure: Pain Catastrophizing Scale
timeFrame: Pre-intervention and pre-patch application
measure: Pain intensity (Induced by Capsaicin)
timeFrame: Throughout the experimental session, every 5 minutes and up to 55 minutes after patch application
Other outcomes:
Locations:
city: Gistrup
country: Denmark
facility: Aalborg University / Center for Neuroplasticity and Pain
Study officials:
affiliation: Aalborg University
name: Thomas Graven-Nielsen, PhD, DMSc
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.