Synaptic mechanisms of pain amplification
Spinal dorsal horn, C-fibre, opioids, optogenetics, microglia
Research interest of the Faculty Member
Our team studies synaptic mechanisms of hyperalgesia (amplified pain sensation). We are interested in cellular and molecular mechanism leading to enhanced excitation or reduced inhibition in spinal nociceptive pathways. We focus on spinal lamina I neurons which constitute key elements of hyperalgesia. We have identified and characterized activity-dependent forms of synaptic long-term potentiation (LTP) at glutamatergic C-fibre synapses and novel activity-independent forms of LTP upon opioid withdrawa. We currently aim at understanding the roles of non-neuronal cells in the spinal cord for synaptic plasticity and identifying strategies to reverse long-term changes in spinal nociception.
Collaborating research groups where PhD Students could perform their research stay
- Dr. Marzia Malcangio, Reader in Neuropharmacology, Wolfson CARD, King's College London, Guys' Campus, London SE1 1UL, UK
- Dr. Christopher Moore, Department of Brain and Cognitive Sciences, MASSACHUSETTS INSTITUTE OF TECHNOLOGY, 77 Massachusetts Ave Cambridge, MA 02139, USA
- Dr. Rebecca Seal, Assistant Professor, Department of Neurobiology, BST3 6058, 3501 Fifth Ave, Pittsburgh, PA 15260, USA
- Dr. Claudia Sommer, Department of Neurology, University of Würzburg, Josef-Schneider-Str. 11, D-97080 Würzburg, Germany
Know-how and infrastructure of the research group
We aim at understanding the role of spinal nociception for pain under physiological, inflammatory and neuropathic conditions. We identified disctinct forms of activity-dependent synaptic long-term potentiation (LTP) in superficial spinal dorsal horn (Ikeda et al., 2003; Ikeda et al., 2006; Drdla et al., 2008) and we discovered a novel form of LTP at C-fibre synapses which is induced upon withdrawal from opioids (Drdla et al., 2009; Heinl et al. 2011). Recently we demonstrated that brief, high opioid doses may reverse established LTP at C-fibres (Drdla-Schutting et al., 2012). We further demonstrated a perceptual correlate of spinal LTP in human volunteers (Klein et al., 2007). We were the first to demonstrate heterosynaptic LTP at spinal GABAergic synapses (Fenselau et al., 2011) and we showed that noradrenaline directly excites GABAergic spinal dorsal horn neurons as a mechanism of descending inhibition (Gassner et al., 2008). We further showedthat impaired spinal GABAergic inhibition leads to the breakdown of somatosensory and modality borders in the spinal dorsal born (Schoffnegger et al., 2008) and we evaluated mechanisms of presynaptic inhibition at spinal C-fibre terminals by opioids (Heinke et al., 2011). Our group is equipped with 5 patch-clamp set-ups, 3 set-ups for in vivo spinal cord recordings, 2 rooms for animal behaviour, a 2-photon laser scanning microscope, a fluorescence microscope and basic laboratory tools e.g. for immunohistochemistry and Westen blotting.