Prof. Dr. Jan Siemens

Institute of Pharmacology, Medical Faculty Heidelberg, Heidelberg University


Gene programs in neuronal spinal cord circuits mediating chronic pain states

FigA07While a lot of progress has been made in deciphering molecules and mechanisms that mediate nociception in primary afferent sensory neurons, much less is known about projection- and inhibitory-interneurons in the dorsal spinal cord. The importance of spinal interneurons in modulating pain perception was already postulated almost 50 years ago in the “Gate Control Theory”. However, today we are confronted with an ever-growing list of morphologically and neurochemically diverse spinal interneurons. The vast heterogeneity raises the question about differential functions of the different interneuron populations in the context of processing painful stimuli.

We aim to categorize spinal neurons based on molecular changes that ensue upon nociceptive stimulation. In particular, we aim to obtain transcriptional signatures of spinal neuron populations that are activated or inhibited in the context of pathological forms of pain.

The long-term goal is to define neuron populations that are involved in mediating and modulating particular pain states.

Specific Goals are:

Identification of Transcriptional signatures of pain chronicity in spinal cord neurons by using the ribosomal capture technique.

Dissecting the contributions of individual neuronal populations to pathological pain states by employing DREADD technology in combination with selected Cre-mouse lines.

Mechanistic analysis of how selected candidates identified in study 1 contribute to the manifestation of chronic pain states using gene knock-down and knock-out mouse 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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