Electrical Intra-cutaneous Half-sine Stimulation for Optimized Preferential C-fiber Activation in an Established Model of Evoked Pain, Hyperalgesia and Allodynia in Humans (25ms HS Stimulation)

Nociceptors in the epidermis are responsible for peripheral pain perception. Mechanical, thermal as well as chemical stimuli can trigger action potentials in nociceptors and thereby pain. Regarding pain, polymodal and "silent" C-fibers are of special interest. Slower depolarisation via sine and half-sine currents preferentially stimulate C-fibers compared to rectangular shaped currents. This study is to compare the development of central sensitization comparing the half-sine wave and the rectangular stimulation, hypothesizing that preferential C fiber stimulation through half-sine currents facilitate the development of secondary hyperalgesia.

This exploratory study is to improve an established pain model by a new stimulation profile that allows preferential activation of C fibers that are of main clinical interest in chronic pain and also to generate a stable secondary hyperalgesia, which is of particular interest in the actual research of acute and chronic pain. It is to investigate if the specific activation of afferent sensory fibers and expected lower current intensities makes it more comfortable for the participant as motor neuron activation is much less pronounced at low current intensities. Therefore it compares the area under the curve (AUC) of hyperalgesia during electrical, intracutaneous 25 ms half-sine wave stimulation at a pain level of the numeric rating scale (NRS) of 6 out of 10 for 65 minutes compared to 500 µs rectangular pulses.

Every volunteer will have two appointments. There will be a "washout" period of at least two weeks between the two appointments. On each day two microdialysis catheters containing internally a stainless steel wire will be inserted intracutaneously on the volar surface of the adominant forearm for a length of approximately 10 mm and at a distance of 5 mm. Before insertion, the catheters are filled with 0.9% saline and after insertion a continuous flow of 0.4 μl/min will be ensured by a syringe pump (Perfusor®) to facilitate conduction and to protect the tissue from potential local pH changes by the direct current. Alternating polarity of the both pulses is used to ensure charge-balanced stimulation.

It is randomly assigned which current form is applied on the first and on the second trial. Subsequently, the stainless steel wire serving as electrodes of the current generator (for 25 ms half-sine stimulation the Digitimer DS5; Digitimer Ltd, Hertfordshire, United Kingdom; and for 500 µs rectangular stimulation the Digitimer DS7A; Digitimer Ltd, Hertfordshire, United Kingdom) are connected. The rectangular pulses are generated by the Digitimer DS7A, which works in combination with a pulse generator (PG 1, Rimkus Medizintechnik, Parsdorf, Germany)