Prof. Dr. Jan Siemens
Institute of Pharmacology, Medical Faculty Heidelberg, Heidelberg University
Prof. Dr. Hilmar Bading
Institute of Neurobiology, Heidelberg University
Activity-regulated gene programs leading to short-term and long-term metabolic plasticity in the spinal cord: role in acute and pathological forms of pain
The dorsal spinal cord is the first relay station for incoming noxious signals that arise from primary somatosensory afferent neurons. Aberrant gene regulation is a major contributor driving the transition from acute to chronic pain states. How pain-induced transcriptional changes shape functional alterations of diverse spinal cell types is only starting to be understood. We have identified a metabolic signalling molecule that is highly up-regulated in astrocytes upon painful stimulation. Preliminary metabolite analysis suggests that major energy-metabolic alterations occur in both spinal glia and neurons in the context of on-going and extended painful stimulation. These findings not only raise the question as to what signals trigger these metabolic alterations but, more generally, how spinal energy metabolism affects pain sensation. We aim to understand how pain-related synaptic activity induces metabolic state changes in neuroglial networks. Based on the uncovered metabolic signaling pathways, we aim to manipulate energy metabolism in the spinal cord in the context of pathological forms of pain in order to understand how metabolite flux affects pain responses in animal models.