Itch and Pain Inhibitory Mechanisms in Humans - evidence for a differential control of nociceptive senses

Abstract: It is known that stimulation of thin nerve afferents can inhibit itch and pain and that the nociceptive systems have a detailed topographical organisation, with subsystems exhibiting specific excitatory and inhibitory receptive fields. On this basis, a new technique was developed, termed Cutaneous Field Stimulation (CFS), that electrically stimulates thin nerve fibers innervating specific skin fields. It was demonstrated that CFS has a robust and long lasting inhibitory effect on experimental itch. Furthermore, CFS selectively affected skin sensations mediated by thin nerve fibers (warmth, cold, itch, heat and mechanical pain). Notably, CFS exhibited a differential effect on different nociceptive skin senses with the strongest depression of C fiber mediated sensations. CFS for 6-10 min sufficed to evoke maximal inhibitory effect on most senses tested. The effects of CFS were independent of the frequency used (1-10 Hz per electrode). Finally, in a controlled and randomised clinical study, CFS induced profound relief of chronic itch lasting for more than 7 h. By contrast, conventional Transcutaneous Electrical Nerve Stimulation (TENS) had only marginal effects on the skin senses tested. CFS, possibly acting through spinal intermodality inhibitory interactions, is thus a powerful method to combat itch. The induction time, effective stimulation frequencies and long duration of the effects suggest underlying mechanisms similar to those of spinal long term depression (LTD) in animals. A hypothesis, "the modality interaction theory", is proposed to explain the differential inhibitory effects on different nociceptive modalities after thin fiber stimulation.