Electrophysiological markers for neuropathic pain in spinal cord injured subjects

Physical disability following spinal cord injury (SCI) is the most striking problem noted by the general public. But for the affected subjects urogenital difficulties or depression and pain are often more burdensome. Pain after SCI can have various reasons but only neuropathic pain below the level of lesion (bNP) is thought to be caused by injury of the spinal nervous tissue. This type of pain is in the focus of this thesis. Once bNP has established it is mostly chronic and medication is generally ineffective. Currently, more and more treatments trying to restore function after SCI enter the clinical trial phase. Besides improving function, however, treatments increasing nerve growth in the spinal cord risk to induce or exacerbate bNP. Therefore, observation of bNP is a crucial factor in such interventional studies. A method to objectively supervise bNP has, however, not yet been established. The spinothalamic tract (STT) mainly transmits nociceptive and temperature information in the spinal cord. This tract was dysfunctional in SCI subjects suffering from bNP in clinical examinations. Nevertheless, STT dysfunction was not predictive for bNP and sensory differences between subjects with and without bNP could not be detected. In contrast to clinical examination which is always subjective and only offers limited resolution, electrophysiological measures allow for a more detailed and objective 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 the conduction velocity of the STT in healthy subjects. Furthermore the CHEP latency depended linearly on the heat pain threshold with 1° C higher threshold leading to approximately 10 ms longer latency. It was hypothesized that the rather low heating rate combined with the time-consuming passive heat spread from skin surface to nociceptors was responsible for this. The second study aimed at clarifying this dependence through comparison of the results of study 1 with those of a theoretical heat transfer model. According to this model, 1° C higher pain threshold leads to approximately 15 ms longer CHEP latency. The close similarity between the experimentally determined (study 1) and the computed dependence, proved the influence of the pain threshold on CHEP latency. Summary Electrophysiological markers for Neuropathic Pain in SCI Subjects 2 Subjects suffering from neuropathic pain (NP) in general and not only in SCI, have lowered EEG peak frequency. It was hypothesized in literature that the reduced EEG peak frequency emerged from thalamic deafferentiation and from the ensuing dysrhythmia in thalamocortical feedback loops. Therefore, the third study investigated EEG peak frequency in addition to STT function and compared both between SCI subjects with and without bNP and controls. The STT function (measured with CHEP) below the level of injury was distinctly impaired in SCI compared to control subjects. Furthermore, the EEG peak frequency was generally lower in the SCI subjects. While the CHEP measurements did not reveal differences between subjects with and without bNP, the EEG peak frequency was lowered in subjects with bNP. This difference, however, was only apparent after the linear dependence of EEG peak frequency from the level of SCI was taken into account. In consideration of this dependence, the EEG peak frequency could in future be helpful to supervise bNP both in studies aiming at restoring function or reducing pain after SCI. Currently, the clinical read-out parameter for STT function is pinprick sensation. In the 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 years after SCI disclosed larger functional STT recovery in subjects suffering from bNP. Despite the different STT functional recovery, the initial and end measurements did not discriminate between subjects with and without bNP. This was in agreement with earlier studies. The results corroborate the above mentioned hypothesis that new therapies intending to promote sensorimotor recovery after SCI could simultaneously induce bNP by boosting recovery of spinothalamic function.