Mechanisms of nociception in neuropathic pain

Aim of this thesis was to explore the mechanisms that account for the development and maintenance of chronic neuropathic pain. This pain type, caused by a lesion to the somatosensory system, can be a debilitating clinical condition which is hard to treat. The shortcomings in current treatment are believed to be associated with the lack of knowledge on the pathogenesis of neuropathic pain.
The first major subject of this thesis focusses on inhibitory mechanisms of pain, especially glycinergic neurotransmission, since spinal disinhibition is a central mechanism for hyperalgesia. In the experiments described in the thesis, a significant role of glycinergic transmission in neuropathic pain could be confirmed. Furthermore, the glycine transporters GlyT1 and GlyT2 could be identified as promising translational targets in the treatment of neuropathic pain. The second major subject of this thesis is the regulation of gene expression in neuropathic pain, specifically the involvement of microRNAs in the somatosensory nervous system. A wide variety of microRNAs possibly involved in the pathophysiology of neuropathic pain has been identified before. In the studies included in this thesis, two further microRNAs, microRNA-1 and microRNA-34a as well as their pain-relevant target proteins are described. Finally, the mechanisms by which systemic administration of the local anesthetic lidocaine can relieve acute and chronic pain are reviewed.
The results obtained from the experiments in this thesis further enhance the knowledge on the molecular basis of the maladaptive processes of painful neuropathy, which may eventually lead to the development of new, mechanisms-oriented treatment options.