title: Evidence of heterosynaptic LTD in the human nociceptive system: superficial skin neuromodulation using a matrix electrode reduces deep pain sensitivity.
abstract: Long term depression (LTD) is a neuronal learning mechanism after low frequency stimulation (LFS). This study compares two types of electrodes (concentric vs. matrix) and stimulation frequencies (4 and 30 Hz) to examine homo- and heterosynaptic effects indirectly depicted from the somatosensory profile of healthy subjects. Both electrodes were compared in a prospective, randomized, controlled cross-over study using 4 Hz as the conditioning LFS compared to 30 Hz (intended sham condition). Quantitative sensory testing (QST) was used to examine 13 thermal and mechanical detection and pain thresholds. Sixteen healthy volunteers (10 women, age 31.0 ± 12.7 years) were examined. Depending on the electrodes and frequencies used a divergent pattern of sensory minus signs occurred. Using LFS the concentric electrode increased thermal thresholds, while the matrix electrode rather increased mechanical including deep pain thresholds. Findings after cutaneous neuromodulation using LFS and a matrix electrode are consistent with the concept of heterosynaptic LTD in the human nociceptive system, where deep pain sensitivity was reduced after superficial stimulation of intraepidermal nerve fibres. Cutaneous neuromodulation using LFS and a matrix electrode may be a useful tool to influence deep pain sensitivity in a variety of chronic pain syndromes.
authors.affiliation: Department of General Practice and Family Medicine, University Hospital, Bonn, Germany; Department of Palliative Medicine, University Hospital, Bonn, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Mücke
authors.affiliation: Department of Palliative Medicine, University Hospital, Bonn, Germany.
authors.forename: Henning
authors.initials: H
authors.lastname: Cuhls
authors.affiliation: Department of Palliative Medicine, University Hospital, Bonn, Germany.
authors.forename: Lukas
authors.initials: L
authors.lastname: Radbruch
authors.affiliation: Department of Anaesthesiology and Intensive Care, University Hospital, Bonn, Germany.
authors.forename: Tobias
authors.initials: T
authors.lastname: Weigl
authors.affiliation: Department of Palliative Medicine, Medical Faculty, RWTH Aachen University, Aachen, Germany.
authors.forename: Roman
authors.initials: R
authors.lastname: Rolke
mesh_terms: D000328:Adult; D004558:Electric Stimulation / Q000295:instrumentation*; D004566:Electrodes; D005260:Female; D020342:Finite Element Analysis; D006801:Humans; D036881:Long-Term Synaptic Depression; D008297:Male; D055595:Mechanical Phenomena; D009474:Neurons / Q000166:cytology; D059225:Nociception / Q000502:physiology*; D017288:Pain Threshold / Q000502:physiology*; D010641:Phenotype; D012867:Skin; D013003:Somatosensory Cortex / Q000166:cytology / Q000502:physiology; D013569:Synapses / Q000502:physiology*; D013696:Temperature