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

Aalborg University

Status: Completed

Conditions: Healthy

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

Study type: Interventional

Funder types: Other

Identifiers

NCT06197529

CHEPS-DMZ-CNAP

Details and patient eligibility

About

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.

Full description

Randomized, cross-over study of four sessions

Enrollment: 18 patients

Sex: All

Ages: 18 to 60 years old

Volunteers: Accepts Healthy Volunteers

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)

Trial design

Primary purpose: Basic Science

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Single Blind

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18 participants in 4 patient groups, including a placebo group

S1 Homeostatic Plasticity-Pain

Experimental group

Description:

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

Treatment:

Other: Homeostatic Plasticity

Drug: Topical alone (Capsaicin 8% Patch)

S1 Homeostatic Plasticity-NoPain

Placebo Comparator group

Description:

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

Treatment:

Other: Homeostatic Plasticity

Other: Placebo Patch

S1 Homeostatic Plasticity-Sham

Sham Comparator group

Description:

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

Treatment:

Other: Homeostatic Plasticity (Sham)

Other: Placebo Patch

M1 Homeostatic Plasticity

Active Comparator group

Description:

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

Treatment:

Other: Homeostatic Plasticity

Other: Placebo Patch