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High-frequency stimulation will be applied on the volar forearm (6-10 cm distal to the cubital fossa). To avoid any confounding effect of handedness, the arm onto which HFS will be applied twice (dominant vs nondominant) will be counterbalanced across participants. HFS will consist of 12 trains of 42 Hz electrical pulses lasting 1 s each. The time interval between each train will be 10 s. The intensity of stimulation will be 5mA. Electrical pulses will be delivered to the skin using a specifically-designed electrode designed: the cathode consists of 16 blunt stainless-steel pins with a diameter of 0.2 mm protruding 1 mm from the base. The 16 pins are placed in a circle with a diameter of 10 mm. The anode consists of a surrounding stainless-steel ring having an inner diameter of 22 mm and an outer diameter of 40 mm. This procedure induces secondary pinprick hyperalgesia (an increase in pinprick sensitivity in a large area of the skin).

High-frequency electrical stimulation

This study is designed to evaluate the method of assessing the and intensity areas of secondary hyperalgesia induced by High Frequency Stimulation (HFS). Measures of the areas of secondary hyperalgesia will take place on two experimental days separated by a minimum of two weeks. Each experimental day, the areas of secondary hyperalgesia will be assessed three times, starting 30 minutes following HFS. Furthermore, the investigators will assess if anxiety, catastrophization, stress and demographic variables modulate the extend of hyperalgesia.

This prospective cohort study is designed to evaluate the method of assessing the areas and intensity of secondary hyperalgesia following High Frequency Stimulation (HFS), and will consist of two experimental days separated by a minimum of two weeks. During the two each session (Day1 and Day2), subjects will go through the HFS procedure on the same forearm. Then, after a 30 minutes break, the area and intensity of secondary hyperalgesia induced by HFS will be assessed three times (Time9-14), with a two-minute break between each assessment.

Before the experiment, subjects will fill two questionnaires by email : the Spielberger Trait anxiety inventory and the Pain catastrophization scale.The first experimental day, the patients will be seated on a chair and informed consent will be gained. Subjects will provide demographic information to the researcher (age, gender, size) (Time1). Then, the forearm skin of the selected arm will be marked with a pen to improve the precision of subsequent measures. The subject will then observe a period of rest for 5 minutes, to provide a baseline measure of heart rate variability.

Next, the patients will be asked to rate the pain induced by pin-prick stimulation in the area surrounding the electrode (Time2).

Following standardized explanation of the HFS procedure, the subject will fill the Spielberger State anxiety inventory (Time5), and HFS will be applied on the volar forearm (6-10 cm distal to the cubital fossa) (Time6). To avoid any confounding effect of handedness, the arm onto which HFS will be applied (dominant vs nondominant) will be counterbalanced across participants. In summary, HFS will consist of 12 trains of 42 Hz electrical pulses (pulse width: 2 ms) lasting 1 s each. The time interval between each train will 10 s. The intensity of stimulation will be 5mA. Heart rate variability during the HFS procedure will be monitored.

After a 25 minutes break the heart rate variability will be assessed a third time during 5 minutes. During the break, subjects will be asked to stay seated, to fill the Pain Catastrophizing scale (short-version) and give a rating from 0-100 for the pain and stress experienced during the HFS procedure (Time7).

Following this break, the area of secondary hyperalgesia will be assessed with a calibrated 128 mN pinprick probe (The Pin Prick, MRC Systems GmbH, Heidelger, Germany) (Time9). Pokes of 1-second duration will be provided at a frequency of 0.5 Hz, starting well outside and approaching the stimulation site with steps of 0,5 cm from 4 different directions towards the application site. Participants will be asked to keep their eyes closed during the entire mapping procedure. Then, participants will rate the pain induced by pin-prick stimulation in the area surrounding the electrode (Time10). This procedure will be conducted three times, with a two-minute break between each assessment (Time 11-14).

The second experimental day (Day2), the procedure will be similar to the first, but informed consent and the Spielberger Trait anxiety inventory and the Pain catastrophization scale will not be filled.

Reliability of Measuring the Area and Intensity of Secondary Hyperalgesia Induced by High Frequency Stimulation

Test-retest Reliability of Measuring the Area and Intensity of Secondary Hyperalgesia Induced by High Frequency Stimulation of Skin Nociceptors

the area of secondary hyperalgesia (cm square) will be assessed with a calibrated 128 mN pinprick probe (The Pin Prick, MRC Systems GmbH, Heidelger, Germany). Pokes of 1-second duration will be provided at a frequency of 0.5 Hz, starting well outside and approaching the stimulation site with steps of 0,5 cm from 4 different directions towards the application site. Participants will be asked to keep their eyes closed during the entire mapping procedure.

participants will rate the pain induced by pin-prick stimulation in the area surrounding the electrode on a numerical rating scale ranging from 0 (no perception) to 100 (maximal pain), with 50 representing the transition from nonpainful to painful domains of sensation

questionnaire assessing the state of anxiety. The score will range from 20 (low state anxiety) to 80 (high state anxiety).

questionnaire assessing the trait of anxiety. The score will range from 20 (low trait anxiety) to 80 (high trait anxiety). This questionnaire will be sent by email to the participant.

questionnaire to assess thoughts and emotions in response to pain. The score will range from 0 (low catastrophization) to 52 (high catastrophization).

questionnaire to assess thoughts and emotions in response to a specific painful event. The score will range from 0 (low catastrophization) to 24 (high catastrophization).

Stress on a scale from 0 (low stress) to 100 (maximal stress).

Lowest intensity at which the participant feels the electrical pulse

changes in the time interval between heart beats through the study completion.

Spots Global Cancer Trial Database for hyperalgesia, secondary