Neuropathic pain in syringomyelia : event-related potentials, psychophysics and spinal diffusion tensor imaging

(eng) Central neuropathic pain (CNP) is one of the most challenging pain problems to treat. Therefore, it has become increasingly important to study the pathological mechanisms for spinal cord lesions leading to the development and maintenance of a central neuropathic pain state. Clinical, electrophysiological and pharmacological studies have suggested that different pain symptoms may be linked with different underlying mechanisms, i.e., spontaneous pain (SP) and evoked pain (EP) may be the clinical correlates of different types of CNP. The general aim of the studies in this thesis was to examine central pain mechanisms using a single condition of central nervous system (CNS) disease and comparing patients according to the type of their symptoms. We hypothesized that within a group of patients with a macroscopically similar CNS lesion, i.e., cervical syringomyelia, different clinical (pain) symptoms would be linked with different pathological mechanisms. Syringomyelia provided an interesting opportunity in this regard, because the syringeal cavity can be localized easily, it affects predominantly sensory spinal tracts that play a major role for the development of neuropathic pain and it may induce SP and/or EP symptoms or even present with no pain symptoms at all. In order to study the mechanisms of central neuropathic pain, a multimodal assessment was performed. This multimodal assessment provided information on the structural and functional status of sensory spinal tracts. Functional investigations appropriate to explore the somatosensory system and in particular the nociceptive system included quantitative sensory testing (QST), laser-evoked potentials (LEP) and somatosensory-evoked potentials (SEP). Furthermore, diffusion tensor imaging with 3D-tractography (DTI-FT) was used to examine the structural status of the spinal cord. In brief, chapter 2 of this thesis describes the validation of DTI-FT for the study of spinal sensory tracts. In Chapter 3 central neuropathic pain mechanisms are examined through the relationship between neuropathic pain and lesions of spinal sensory tracts. Oscillatory brain rhythms and their influence on neuropathic pain are explored in Chapter 4. Chapter 5 describes the use of supraliminal thermonociceptive stimulations to quantify the intensity of experimentally-evoked pain in patients with syringomyelia. How the modulation of laser-evoked potentials by response inhibition may allow recognizing the presence of supracortical modulation of nociceptive brain processes, is described in Chapter 6. Further reflections on the use of multimodal assessments of the somatosensory system, on future research protocols in central neuropathic pain and on the possibilities of diffusion tensor imaging can be found in Chapter 7 of this manuscript. A new method to analyze somatosensory event-related potentials, i.e., the automated single trial approach, is explained and validated in Appendix B.