Electrophysiological Markers for Neuropathic Pain in Spinal Cord Injured Subjects

[摘要] Physical disability following spinal cord injury (SCI) is the most striking problem notedby the general public. But for the affected subjects urogenital difficulties ordepression and pain are often more burdensome. Pain after SCI can have variousreasons but only neuropathic pain below the level of lesion (bNP) is thought to becaused by injury of the spinal nervous tissue. This type of pain is in the focus of thisthesis. Once bNP has established it is mostly chronic and medication is generallyineffective. Currently, more and more treatments trying to restore function after SCIenter the clinical trial phase. Besides improving function, however, treatmentsincreasing nerve growth in the spinal cord risk to induce or exacerbate bNP.Therefore, observation of bNP is a crucial factor in such interventional studies. Amethod to objectively supervise bNP has, however, not yet been established.The spinothalamic tract (STT) mainly transmits nociceptive and temperatureinformation in the spinal cord. This tract was dysfunctional in SCI subjects sufferingfrom bNP in clinical examinations. Nevertheless, STT dysfunction was not predictivefor bNP and sensory differences between subjects with and without bNP could not bedetected. In contrast to clinical examination which is always subjective and onlyoffers limited resolution, electrophysiological measures allow for a more detailed andobjective investigation.The novel electrophysiological method of contact heat evoked potentials (CHEP)measures STT function. Establishment of this method was the goal of the first study.The painful stimulation on locations along the spine allowed the calculation of theconduction velocity of the STT in healthy subjects. Furthermore the CHEP latencydepended linearly on the heat pain threshold with 1° C higher threshold leading toapproximately 10 ms longer latency. It was hypothesized that the rather low heatingrate combined with the time-consuming passive heat spread from skin surface tonociceptors was responsible for this.The second study aimed at clarifying this dependence through comparison of theresults of study 1 with those of a theoretical heat transfer model. According to thismodel, 1° C higher pain threshold leads to approximately 15 ms longer CHEPlatency. The close similarity between the experimentally determined (study 1) and thecomputed dependence, proved the influence of the pain threshold on CHEP latency.SummaryElectrophysiological markers for Neuropathic Pain in SCI Subjects 2Subjects suffering from neuropathic pain (NP) in general and not only in SCI, havelowered EEG peak frequency. It was hypothesized in literature that the reduced EEGpeak frequency emerged from thalamic deafferentiation and from the ensuingdysrhythmia in thalamocortical feedback loops. Therefore, the third studyinvestigated EEG peak frequency in addition to STT function and compared bothbetween SCI subjects with and without bNP and controls. The STT function(measured with CHEP) below the level of injury was distinctly impaired in SCIcompared to control subjects. Furthermore, the EEG peak frequency was generallylower in the SCI subjects. While the CHEP measurements did not reveal differencesbetween subjects with and without bNP, the EEG peak frequency was lowered insubjects with bNP. This difference, however, was only apparent after the lineardependence of EEG peak frequency from the level of SCI was taken into account. Inconsideration of this dependence, the EEG peak frequency could in future be helpfulto supervise bNP both in studies aiming at restoring function or reducing pain afterSCI.Currently, the clinical read-out parameter for STT function is pinprick sensation. Inthe fourth study this pinprick sensation was traced over the first year after SCI.Comparison of this STT function with the bNP state of the same subjects 2-5 yearsafter SCI disclosed larger functional STT recovery in subjects suffering from bNP.Despite the different STT functional recovery, the initial and end measurements didnot discriminate between subjects with and without bNP. This was in agreement withearlier studies. The results corroborate the above mentioned hypothesis that newtherapies intending to promote sensorimotor recovery after SCI could simultaneouslyinduce bNP by boosting recovery of spinothalamic function.

[发布机构] University of Zurich / ETH Zurich

[效力级别] 570 Life sciences

[关键词] Brain Research Institute;570 Life sciences;biology;610 Medicine & health