Pain has an enormous impact on the lives of patients with chronic pain. Under healthy conditions, pain is caused by the activation of nociceptive Aδ- and C-fibers following actual or potential tissue damage. Patients with chronic neuropathic pain experience pain as a result of spontaneous activity and associated sensitization of neurons in the nociceptive system. Patients with chronic nociplastic pain experience pain as a result of sensitization and decreased inhibition of neurons in the nociceptive system. Diagnosis of nociplastic pain is complicated and usually takes several years. Treatment of neuropathic and nociplastic pain is challenging and relief is often not sufficient. A mechanism-based approach could enable early diagnosis and effective treatment of neuropathic, nociplastic and mixed pain patients. Therefore, the goal of this thesis was ‘to develop combined psychophysical and neurophysiological tools for mechanism-based observation of impaired nociceptive processing’. The strategy was to combine psychophysical methods with neurophysiological techniques to provide mechanism-based information on nociceptive function. The studies presented in this thesis describe the technical development and exploration of a method to observe nociceptive processing using intra-epidermal electric detection thresholds and evoked potentials, including the exploration of feasibility and utility of this method in a clinical setting. In addition, other novel technologies are explored, which could improve identification of impaired nociceptive processing in future projects.

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