Network insight of nociception and pain in Parkinson’s disease – PPNet

Parkinson’s disease is a neurological disorder characterized by both motor and non-motor symptoms, including pain which further deteriorates the quality of life of patients. Central neuropathic pain and altered nociceptive sensitivity in these patients are thought to arise from central nervous system dysfunctions, suggesting that brain circuits enabling pain perception and processing may be disorganized. While abnormal nociceptive processing has been reported in some cortical structures involved in pain, there is still no clear pathophysiological mechanism to explain these specific symptoms. The PPNet project aims at investigating cortical and subcortical pathophysiological mechanisms at the origin of pain in Parkinson's disease, using behavioral, electrophysiological, chemogenetic, optogenetic and neuroimaging approaches. To reach this aim, PPNet gathers researchers from 3 French laboratories experts in the field: the “Institut des Neurosciences Cellulaires & Intégratives” (Strasbourg), the “Grenoble Institute of Neuroscience” (Grenoble) and the “Institut des Maladies Neurodégénératives” (Bordeaux). The project synergy and added value relies on a coordinated choice of models, tests and procedures between the Partners. The contribution of potentially keys brain structures and networks will be explored using murine models of PD to reach a mechanistic level of understanding: the substantia nigra pars reticulata to periaqueductal grey to subthalamic nucleus pathway, the subthalamic nucleus to cortical areas pathways, the GABA tail of the ventral tegmental area receiving nociceptive parabrachial information and controlling the remaining aminergic neurons. The project will address the neuroanatomy of these actors, their change in activity and processing of nociceptive information in the pathological state, and their role in the behavioral symptoms. By improving our understanding of pain in Parkinson's disease, PPNet should also contribute in paving the way to search for improved therapeutics.