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 after heterotopic LFS did not differ from habituation effects in Control experiment without LFS. Heterotopic pain perception was not affected. This part demonstrated homotopic organization of LTD. Investigation of LFS effect on sensory and affective pain perception in the second part of the study was performed on 20 healthy volunteers, who were asked to rate their pain on multidimensional assessment including Verbal Rating Scale of perceived stimulus intensity and unpleasantness and Pain Perception Scale with sensory and affective items. After LFS, pain perception ratings were reduced as compared to Pre series and Control experiments. During LFS, ratings decreased. Factor analysis of sensory items of the Pain Perception Scale revealed sole reduction of superficial sharp pain perception after LFS in contrast to Control experiment. Perception of deep rhythmic pain decreased over time. Deep constant pain and superficial heat pain were not affected. This study showed sustained LTD of sensory and affective components of pain. Reduction of sharp pain points to A-delta fiber mediated LTD. In the third part of the thesis, LFS effects on cerebral activation were investigated in 17 healthy male volunteers by functional magnetic resonance imaging. Volunteers rated sensory and affective pain perception. Electrical test stimulation activated brain areas involved in sensory (primary and secondary somatosensory cortex, posterior insula) and affective (anterior cingulate cortex, anterior insula) pain processing. After LFS, activity was significantly reduced. There was no change during Control experiments. Sensory and affective pain rating solely decreased after LFS. Pain relief was correlated with increased activity after LFS in rostral part of anterior cingulate cortex, anterior insula, striatum, frontal and temporal cortex. This part revealed LTD of pain-related cerebral activation, involving sensory and affective processes. Increased brain activation after LFS suggested involvement of endogenous pain modulatory systems leading to stronger LTD. The present thesis indicated sustained reduction of nociception and pain after LFS for at least one hour. Homotopic A-delta fiber mediated LTD was expressed by declined somatosensory evoked potentials, sensory and affective pain perception rating and pain-related cerebral activation. Reduction of nociceptive processing might be due to peripheral effects on the first nociceptive synapse as it is indicated from in vitro studies. The magnitude of pain relief was correlated with increased brain activation after LFS, suggesting an involvement of endogenous pain modulatory pathways. This thesis was an important step towards the understanding of LTD in humans. Detailed knowledge about LTD is a prerequisite in order to use LFS as therapy in chronic pain patients in future.

Grantor dc:publisher

Publikationsserver der RWTH Aachen University

Year dc:date

2010

Author dc:creator

• Rottmann, Silke

Contributors dc:contributor

• Ellrich, Jens

• info:eu-repo/classification/ddc/570
• Mehrdimensionale Schmerzskala
• Neuronale Plastizität
• Elektroencephalographie
• Homotopie
• Biowissenschaften, Biologie
• Schmerzgedächtnis
• elektrische Niederfrequenzstimulation
• konzentrische Elektrode
• funktionelle Magnetresonaztomographie
• electrical low-frequency stimulation
• concentric electrode
• pain memory
• plasticity
• functional magnetic resonance imaging

Statement dc:rights

• info:eu-repo/semantics/openAccess

Language dc:language

eng

Identifier

https://publications.rwth-aachen.de/search?p=id:%22RWTH-CONV-112682%22

OAI record oai:identifier

https://publications.rwth-aachen.de/oai2d?verb=GetRecord&metadataPrefix=oai_dc&identifier=oai%3Apublications.rwth-aachen.de%3A50126