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.

Project related Publications (not necessarily from my group):

Peer-reviewed publications: (past and present CRC PIs are marked in bold)

Bas-Orth C, Tan YW, Lau D, Bading H. Synaptic Activity Drives a Genomic Program That Promotes a Neuronal Warburg Effect. J Biol Chem 2017;292(13):5183-5194.

Chandrasekar A, Olde Heuvel F, Tar L, Hagenston AM, Palmer A, Linkus B, Ludolph AC, Huber-Lang M, Boeckers T, Bading H, Roselli F. Parvalbumin Interneurons Shape Neuronal Vulnerability in Blunt TBI. Cereb Cortex 2018. Hagenston AM, Simonetti M. Neuronal calcium signaling in chronic pain. Cell Tissue Res 2014;357(2):407-426.

Hanack C, Moroni M, Lima WC, Wende H, Kirchner M, Adelfinger L, Schrenk-Siemens K, Tappe-Theodor A, Wetzel C, Kuich PH, Gassmann M, Roggenkamp D, Bettler B, Lewin GR, Selbach M, Siemens J. GABA blocks pathological but not acute TRPV1 pain signals. Cell 2015;160(4):759-770.

Litke C, Bading H,

Mauceri D. Histone deacetylase 4 shapes neuronal morphology via a mechanism involving regulation of expression of vascular endothelial growth factor D. J Biol Chem 2018;293(21):8196-8207. Mauceri D, Hagenston AM, Schramm K, Weiss U, Bading H. Nuclear Calcium Buffering Capacity Shapes Neuronal Ar-chitecture. J Biol Chem 2015;290(38):23039-23049.

Rostock C, Schrenk-Siemens K, Pohle J, Siemens J. Human vs. Mouse Nociceptors - Similarities and Differences. Neu-roscience 2018;387:13-27.

Schrenk-Siemens K, Wende H, Prato V, Song K, Rostock C, Loewer A, Utikal J, Lewin GR, Lechner SG, Siemens J. PIEZO2 is required for

Simonetti M, Hagenston AM, Vardeh D, Freitag HE, Mauceri D, Lu J, Satagopam VP, Schneider R, Costigan M, Bading H, Kuner R. Nuclear calcium signaling in spinal neurons drives a genomic program required for persistent inflam-matory pain. Neuron 2013;77(1):43-57.

Song K, Wang H, Kamm GB, Pohle J, Reis FC, Heppenstall P, Wende H, Siemens J. The TRPM2 channel is a hypotha-lamic heat sensor that limits fever and can drive hypothermia. Science 2016;353(6306):1393-1398.

  • Shiying Lu ; (Doctoral student)

  • Hagen Wende ; (Senior Scientist)



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    Congratulations to SFB 1158 Project Leader, Professor Carmen Ruiz de Almodóvar, who has successfully obtained an ERC Consolidator Grant!


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  • Annual International Research Symposium

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    The Heidelberg Pain Consortium goes into the second funding period.

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