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

Healthy Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT06197529
• Other study ID #: CHEPS-DMZ-CNAP
• Status: Completed
• Phase: N/A
• Start date: November 21, 2023
• Est. completion date: March 4, 2024

Study information

• Verified date: May 2024
• Source: Aalborg University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

Randomized, cross-over study of four sessions

Recruitment information / eligibility

• Status: Completed
• Enrollment: 18
• Est. completion date: March 4, 2024
• Est. primary completion date: March 4, 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 60 Years

Eligibility

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)

Related Conditions & MeSH terms

• Healthy

Intervention

Other:
• Homeostatic Plasticity
Anodal tDCS S1/M1

Drug:
• Topical alone (Capsaicin 8% Patch)
4x4 patch

Other:
• Placebo Patch
4x4 patch
• Homeostatic Plasticity (Sham)
sham Homeostatic Plasticity protocol over S1

Locations

Country	Name	City	State
Denmark	Aalborg University / Center for Neuroplasticity and Pain	Gistrup

Sponsors (1)

Lead Sponsor	Collaborator
Aalborg University

Country where clinical trial is conducted

Denmark, 

References & Publications (7)

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. — View 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. — View 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. — View 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. — View 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. — View 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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Contact Heat Evoked Potentials	Baseline (Evoked Potentials after stimulus onset from electroencephalographic channels)	Pre-patch application
Primary	Contact Heat Evoked Potentials	Post-Patch (Evoked Potentials after stimulus onset from electroencephalographic channels)	30 minutes after patch application
Primary	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
Primary	Contact Heat Evoked Potentials	Post-HP (Evoked Potentials after stimulus onset from electroencephalographic channels)	0 minutes after homeostatic plasticity induction
Primary	Contact Heat Evoked Potentials	Post-HP+10 minutes (Evoked Potentials after stimulus onset from electroencephalographic channels)	10 minutes after the homeostatic plasticity protocol
Secondary	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
Secondary	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 second block of CHEP stimulation
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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