River Publishers Series in
Author: Kerstin Jung, Department of Health Science and Technology, Aalborg University, Denmark
Available: December 2011
Long-term potentiation (LTP) and long-term depression (LTD) represent synaptic plasticity models that are involved in learning and memory processes. LTP can be induced by electrical stimulation with high-frequency. In contrast, application of low-frequency stimulation (LFS) leads to a decrease of synaptic transmission referred to as LTD. Synaptic plasticity was also 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 in order to attenuate or even erase this pain memory. However, information about LTD of noci-ceptive processing and pain perception in human is still rare. Thus, the aim of the present the-sis was a further, more detailed investigation of LTD of spinal nociception and pain in healthy humans.
The first study investigated the optimum stimulation paradigm for inducing LTD and demon-strated a protocol with 1 Hz, 1200 pulses and 4-fold pain threshold as most effective for in-ducing strong LTD effect at the spinal level. It was also shown that established LTD after single LFS could be amplified by an additional second LFS. The second study focused on the spatial organization of LTD. In order to allow more precise conclusions about the size of skin area that is involved in LTD, different electrode designs were applied on the low back and the forearm. A sustained pain reduction after LFS to different receptive fields (RF) on the forearm and low back was observed. The most efficient LTD effect was obtained in the central and marginal area of the RF compared to the less affected outlying area. The third study examined changes in activation pattern of pain-related brain areas after LFS. Dipole source modeling was performed in order to obtain information about involved brain generators. Dipole modeling indicated a significant decrease and a posterior shift of the source generator in the anterior cingulate cortex after LFS. These results indicate possible neuroplastic changes within the involved pain pathways evoked by LTD induction.
Clarifying possible mechanisms that contribute to LTD induction is a further step to elucidate precise mechanisms involved in LTD induction for qualifying this approach for neuromodu-latory treatment of pain.