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

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

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)