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.


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