HFAC Stimulation (30-50 Kilohertz) in Healthy Volunteers (High Frequency Alternating Current Stimulation)

It will be assessed as a direct measure of blockade of the large diameter sensory fibers Aα and Aβ over the non-dominant hand. Two recording electrodes (model Repusi-Gwc-1.5r reusable conductive ring electromyography electrodes) shall be used and placed on the index finger, the anode over the metacarpophalangeal joint and the cathode over the distal interphalangeal joint. The ground electrode shall be placed over the styloid process of the radius. The location of the median nerve in the forearm is then identified by transcutaneous bipolar stimulation. To evoke the action potential, supramaximal stimuli will be applied using a pulse width of 1000µs at a frequency of 1 Hz. The average of a train of 10 pulses will be collected for subsequent analysis.

It will be assessed as an indirect measure of the blockade of the motor fibers (Aα motor neurons) of the median nerve. Assessment of palmar pincer isometric peak force of the non-dominant hand (distal phalanx of the second and third finger with the distal phalanx of the first finger) shall be performed with a pincer dynamometer (Pinch meter P200 Biometric LTD). Three measurements of the peak isometric pincer force in Kg/f shall be recorded and the average of the three measurements shall be taken as the peak force value. The subject will hold the force for at least 3 seconds and it will be performed progressively until the maximum peak is reached, with at least 15 seconds of recovery between measurements. This measurement has shown excellent validity and reliability for measuring strength in median nerve blocks and neurological pathologies.

This will be assessed as an indirect measure of the blockage of the Aβ sensory fibers of the median nerve. Two-point tactile discrimination between two points will be carried out on the anterior face of the distal phalanx of the third finger with an esthesiometer (Baseline®). This evaluation will be carried out according to the protocol described by Sang W. et al (2017), instructing the subject to report when they perceive a point or two. The protocol begins with a descending trial with the esthesiometer initially set at a distance of 10 mm and decreasing by 1 mm until the participant reports perceiving a single point. When that happens, several stimuli around that threshold will be given randomly, including stimuli with a single tip. If the subject correctly identifies two of three stimuli while not at a shorter distance, that will be considered their final discrimination threshold.

It will be assessed as an indirect measure of the blockade of the type C amyelinic sensory fibers of the median nerve. Hot thermal stimuli will be applied over the thenar eminence in the palmar aspect of the non-dominant hand (dermatome innervated by the median nerve), using a 9 cm2 thermoelectric cell (TSA 2. Medoc, Israel). Three temperature ramp-up measurements will be performed with a time between tests of 30 seconds. The thermal pain threshold to heat shall be determined by the limit method and the mean value of the 3 measurements shall be taken as the threshold value. The starting temperature shall be 32°C and the rate of ascent shall be 1°C/s, with a rate of descent of 8,5°C/s. Subjects shall be instructed to press the device with the contralateral hand when the warm thermal sensation becomes painful and the temperature of the applicator shall automatically decrease. For safety reasons, 50°C shall be set as the cut-off temperature.

A doppler temperature and perfusion monitor (Moor Instruments model DRT4) with a recording sensor placed on the palmar side over the head of the third metacarpal will be used to record skin temperature of the non-dominant hand. An external analog thermometer shall be used to record the ambient temperature.

In order to assess the adverse effects and the subjective perception of the participants, a standardized questionnaire was developed. In this questionnaire, ten items have been established with response options (YES/NO) in relation to heat, cold, sweating, tingling, pain (burning/punching/electrical, superficial/deep), numbness, numbness, stiffness/shrinking, heaviness and/or weakness, together with the area in which they are perceived and an open item in which other effects or sensations that the participant has perceived will be collected. The unpleasantness of the intervention will also be assessed using a 10 cm visual analog scale where 0 corresponds to "not at all unpleasant" and 10 to "as unpleasant as you could receive".

Immediately after stimulation intervention (15 min) (30, 40, 50 kHz and sham) the success of blinding will be assessed through five response options: "What type of intervention do you think you have received?" I strongly believe I have received an experimental treatment/ I slightly believe I have received an experimental treatment/ I strongly believe I have received a placebo/ I slightly believe I have received a placebo/ don't know or no answer.