Long-term depression of nociception and pain in healthy volunteers

Synaptic plasticity, including long-term potentiation (LTP) and long-term depression (LTD), represents a cellular model of learning and memory. LTP, a long-lasting increase of synaptic strength, can be induced by electrical stimulation with a high frequency. Low-frequency stimulation (LFS) leads to a decrease of synaptic transmission referred to as LTD. Synaptic plasticity was shown in the nociceptive system. LTP is suggested to be involved in central sensitization of pain, leading to a so-called pain memory. As LFS is able to reverse LTP, it might be useful to attenuate or even erase pain memory. Therefore it is of great interest to investigate LFS-induced LTD in humans, in order to use it in future therapy of chronic pain. So far, most studies were conducted in animals, showing sustained homosynaptic LTD after LFS of spinal afferents. The few studies in humans investigated the influence of LFS on trigeminal reflexes, evoked potentials and general pain perception. Present thesis is dealing with a detailed investigation of LTD in spinal nociceptive processing in healthy human. In all parts nociceptive A-delta fibers were electrically stimulated by a concentric electrode. Painful test stimulation series were applied before (Pre) and after (Post) conditioning LFS (1 Hz, 20 min) to the hand dorsum. In Control experiments with the same volunteers no LFS was applied, but stimulation was interrupted. LFS effect was examined by electrophysiological, psychophysical and brain imaging methods. In the first part of the thesis, putative homotopy of LTD was investigated in 30 volunteers by alternating application of test stimulation series unilateral to radial and ulnar side of right hand dorsum or bilateral to radial side of right and left hand dorsum. Conditioning LFS was applied to radial side of right hand dorsum. Somatosensory evoked cortical potential were recorded and volunteers rated stimulus intensity. After homotopic LFS, amplitude of cortical potential and pain rating significantly decreased. Amplitude reduction ...