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Prof. Dr. Martin Schmelz

Translational pain research

In this research group sensitization of primary afferent nociceptors is investigated as one mechanism for inflammatory and neuropathic chronic pain. We focus on translational studies using single fiber recording techniques in chronic pain patients, human volunteers and large animals (pig) combined with functional and structural investigations of skin innervation in-vivo and in cell-culture.

  • Cellular porcine model
    Patch-clamp and histochemistry of porcine dorsol root ganglion cells to characterize different nociceptor classes. Development of in-vitro model of nerve endings separated from the cell body and coculture with keratinocytes.
  • Porcine single fiber recordings
    Characterization of different afferent nerve fiber classes and modulation of axonal excitability using standard teased fiber techniques in the pig saphenous nerve. Effects of locally applied growth factors on excitability of nerve endings and axonal excitability.
  • Porcine neurogenic inflammation
    Development of experimental models of peripheral sensitization by UVB irradiation with the objective readout of axon reflex erythema measured by laser Doppler imaging. Microdialysis in the sunburn to assess levels of inflammatory mediators involved in peripheral sensitization.
  • Human pain models
    Characterization of human pain models for peripheral (UVB irradiation) and central (electrical pain and hyperalgesia model) sensitization by pharmacological intervention. Objective assessment of cutaneous unmyelinated innervation by electrically induced axon reflex erythema and electrically induced axon reflex sweating.
  • Chronic pain patients
    Microneurographic characterization of neuropathic changes in primary afferent fibers linked to chronic pain. Correlation of functional and structural changes in neuropathic pain by using skin biopsies, quantitative sensory testing, and electrically induced axon reflex measurements.
Tip of a microneurography needle inserted into a peripheral nerve fascicle is shown (upper left) in close proximity to bundles of unmyelinated fibers. This arrangement is used to record single C-fibers in human. In animals, minute fascicles are dissected and placed on a recording electrode (upper right). Discharge patterns to depolarizing ramp stimuli massively differ between C-fiber classes (bottom).

Selection of recent publications

  1. Kist AM, Sagafos D, Rush AM, Neacsu C, Eberhardt E, Schmidt R, Lunden LK, Orstavik K, Kaluza L, Meents J, Zhang Z, Carr TH, Salter H, Malinowsky D, Wollberg P, Krupp J, Kleggetveit IP, Schmelz M, Jorum E, Lampert A, Namer B. SCN10A Mutation in a Patient with Erythromelalgia Enhances C-Fiber Activity Dependent Slowing. PloS one 2016;11(9):e0161789.
  2. Namer B, Orstavik K, Schmidt R, Kleggetveit IP, Weidner C, Mork C, Kvernebo MS, Kvernebo K, Salter H, Carr TH, Segerdahl M, Quiding H, Waxman SG, Handwerker HO, Torebjork HE, Jorum E, Schmelz M. Specific changes in conduction velocity recovery cycles of single nociceptors in a patient with erythromelalgia with the I848T gain-of-function mutation of Nav1.7. Pain 2015;156(9):1637-1646.
  3. Rukwied R, Weinkauf B, Main M, Obreja O, Schmelz M. Inflammation meets sensitization--an explanation for spontaneous nociceptor activity? Pain 2013;154(12):2707-2714.
  4. Klusch A, Ponce L, Gorzelanny C, Schafer I, Schneider SW, Ringkamp M, Holloschi A, Schmelz M, Hafner M, Petersen M. Coculture model of sensory neurites and keratinocytes to investigate functional interaction: chemical stimulation and atomic force microscope-transmitted mechanical stimulation combined with live-cell imaging. J Invest Dermatol 2013;133(5):1387-1390.
  5. Hirth M, Rukwied R, Gromann A, Turnquist B, Weinkauf B, Francke K, Albrecht P, Rice F, Hagglof B, Ringkamp M, Engelhardt M, Schultz C, Schmelz M, Obreja O. Nerve growth factor induces sensitization of nociceptors without evidence for increased intraepidermal nerve fiber density. Pain 2013;154(11):2500-2511.
  6. Camprubi-Robles M, Mair N, Andratsch M, Benetti C, Beroukas D, Rukwied R, Langeslag M, Proia RL, Schmelz M, Ferrer Montiel AV, Haberberger RV, Kress M. Sphingosine-1-phosphate-induced nociceptor excitation and ongoing pain behavior in mice and humans is largely mediated by S1P3 receptor. JNeurosci 2013;33(6):2582-2592.
  7. Kleggetveit IP, Namer B, Schmidt R, Helas T, Ruckel M, Orstavik K, Schmelz M, Jorum E. High spontaneous activity of C-nociceptors in painful polyneuropathy. Pain 2012;153(10):2040-2047.
  8. Schweizerhof M, Stosser S, Kurejova M, Njoo C, Gangadharan V, Agarwal N, Schmelz M, Bali KK, Michalski CW, Brugger S, Dickenson A, Simone DA, Kuner R. Hematopoietic colony-stimulating factors mediate tumor-nerve interactions and bone cancer pain. NatMed 2009;15(7):802-807.
  9. Ikoma A, Steinhoff M, Stander S, Yosipovitch G, Schmelz M. The neurobiology of itch. NatRevNeurosci 2006;7(7):535-547.
  10. Yosipovitch G, Greaves M, Schmelz M. Itch. Lancet 2003;361:690-694.

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