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):
  • Molecular Profiling of Activated Neurons by Phosphorylated Ribosome Capture. Cell 151, 1126–1137, 2012

  • Molecular profiling of activated olfactory neurons identifies odorant receptors for odors in vivo. Nature Neuroscience, 18, 1446-54, 2015

  • Identification of Spinal Circuits Transmitting and Gating Mechanical Pain. Cell 159, 1417–1432, 2014

  • GABA blocks pathological but not acute TRPV1 pain signals. Cell. 2015 Feb 12;160(4):759-70

  • Gangadharan V. , Kuner R.
  • . Unravelling Spinal Circuits of Pain and Mechanical Allodynia.
  • Neuron. . 2015 Aug 19;87(4):673-5. doi: 10.1016/j.neuron.2015.08.013.PubMed PMID: 26291151.
  • Körber C, Horstmann H, Venkataramani V, Herrmannsdörfer F, Kremer T, Kaiser M, Schwenger DB, Ahmed S, Dean C, Dresbach T, Kuner T.
  • . Modulation of Presynaptic Release Probability by the Vertebrate-Specific Protein Mover.
  • Neuron. . 2015 Aug 19;87(4):673-5. doi: 10.1016/j.neuron.2015.08.013.PubMed PMID: 26291151.
  • Körber C, Horstmann H, Venkataramani V, Herrmannsdörfer F, Kremer T, Kaiser M, Schwenger DB, Ahmed S, Dean C, Dresbach T, Kuner T.
  • . Modulation of Presynaptic Release Probability by the Vertebrate-Specific Protein Mover.
  • Neuron. . 2015 Aug 5;87(3):521-33. doi: 10.1016/j.neuron.2015.07.001. Epub 2015 Jul 23. PubMed PMID:26212709.
  • Lau D, Bengtson CP, Buchthal B, Bading H.
  • . BDNF Reduces Toxic Extrasynaptic NMDA Receptor Signaling via Synaptic NMDA Receptors and Nuclear-Calcium-Induced Transcription of inhba/Activin A
  • Cell Rep. . 2015 Aug 25;12(8):1353-66. doi:10.1016/j.celrep.2015.07.038. Epub 2015 Aug 13. PubMed PMID: 26279570
  • Selvaraj D, Gangadharan V. , Michalski CW, Kurejova M, Stösser S, Srivastava K, Schweizerhof M, Waltenberger J, Ferrara N, Heppenstall P, Shibuya M, Augustin HG, Kuner R. .,
  • . A Functional Role for VEGFR1 Expressed in Peripheral Sensory Neurons in Cancer Pain.
  • Cancer Cell 2015 Jun 8;27(6):780-96. doi:10.1016/j.ccell.2015.04.017. Erratum in: Cancer Cell. 2015 Aug 10;28(2):270.PubMed PMID: 26058077; PubMed Central PMCID: PMC4469373.
  • Vicuña L, Strochlic DE, Latremoliere A, Bali KK, Simonetti M, Husainie D, Prokosch S, Riva P, Griffin RS, Njoo C, Gehrig S, Mall MA, Arnold B, Devor M, Woolf CJ, Liberles SD, Costigan M, Kuner R.
  • . The serine protease inhibitor SerpinA3N attenuates neuropathic pain by inhibiting T cell-derived leukocyte elastase
  • Nat Med 2015 May;21(5):518-23. doi: 10.1038/nm.3852. Epub 2015 Apr 27. PubMed PMID: 25915831; PubMed Central PMCID: PMC4450999.
  • Bäumer P, Weiler M, Bendszus M, Pham M.
  • . Somatotopic fascicular organization of the human sciatic nerve demonstrated by MR neurography.
  • Neurology . 2015 Apr 28;84(17):1782-7. doi: 10.1212/WNL.0000000000001526. Epub 2015 Apr 3. PubMedPMID: 25841030; PubMed Central PMCID: PMC4424125.
  • Lu J, Luo C, Bali KK, Xie RG, Mains RE, Eipper BA, Kuner R.
  • . A role for Kalirin-7 in nociceptive sensitization via activity-dependent modulation of spinal synapses
  • Nat Commun .2015 Apr 13;6:6820. doi: 10.1038/ncomms7820. PubMed PMID: 25865668; PubMed Central PMCID: PMC4403379.
  • Arcourt A , Lechner SG.
  • . Peripheral and spinal circuits involved in mechanical allodynia.
  • Pain .2015 Feb;156(2):220-1. doi: 10.1097/01.j.pain.0000460818.62406.38. Review. PubMed PMID: 25599442.
  • 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 Feb 12;160(4):759-70. doi: 10.1016/j.cell.2015.01.022. PubMed PMID: 25679765.
  • People:
    • Shiying Lu ; (Doctoral student)

    • Hagen Wende ; (Senior Scientist)

    Links:
     

    http://www.siemenslab.de/

    News

    • Annual International Research Symposium 2018

      Annual International Research Symposium 2018

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      At the German Pain Congress (Deutscher Schmerzkongress), SFB Scientist Dr. Linette Tan was honored with this year's prize for basic science. Other scientists working in the Heidelberg Pain Consortium also received prizes.

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    • Nitin Agarwal wins Rising Star Grant

       Dr. Nitin Agarwal has been awarded a grant in this year's "Rising star initiative", presented by Ono Pharmaceutical Co. Ltd.

       


       
    • Grant writing workshop

      In July 2018, the Heidelberg Pain Consortium hosted a grant writing workshop for trainees and postdocs 

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