A novel role for opioids: the reversal of established hyperalgesia and chronic pain by synaptic depotentiation LS07-040 Jürgen Sandkühler, Ruth Drdla-Schutting, Burkhard Gustorff Project-team Univ.-Prof. Dr. Jürgen Sandkühler Ass.-Prof. Mag. Ruth Drdla-Schutting, PhD Univ. –Prof. Dr. Burkhard Gustorff, DEAA A synaptic amplifier of pain at the spinal level Noxious stimulus Opioid receptors at the spinal relay for nociception Spinal dorsal horn µ-Opioid receptor IR A brief, high-dose opioid application persistently reverses LTP Drdla-Schutting et al., Science 335 (2012) 235 A brief, high-dose opioid application persistently reverses LTP Drdla-Schutting et al., Science 335 (2012) 235 Mechanisms of LTP reversal by opioids Drdla-Schutting et al., Science 335 (2012) 235 Opioids reverse hyperalgesia in behaving animals Drdla-Schutting et al., Science 335 (2012) 235 Capsaicin High-dose opioid Brief high-dose opioid treatment persistently reduces pain ratings in patients Summary and Impact Novel opioid mechanism: Single, high-dose opioid application reverses • established LTP at nociceptive synapses • Hyperalgesia • pain ratings in patients with post-herpetic neuralgia Immediate and effective pain treatment Forms of chronic pain involving LTP might benefit Causal therapy for some forms of enhanced pain sensitivity Output of the project Drdla R, Sandkühler J (2008) Long-term potentiation at C-fibre synapses by low-level presynaptic activity in vivo. Mol Pain 4:18. 2008 Sandkühler J (2009) Models and mechanisms of hyperalgesia and allodynia. Physiol Rev 89:707-758. 2009 Heinke B, Gingl E, Sandkühler J (2011) Multiple targets of µ-opioid receptor mediated presynaptic inhibition at primary afferent Aδ- and C-fibers. J Neurosci 31:1313-1322. 2011 Drdla-Schutting R, Benrath J, Wunderbaldinger G, Sandkühler J (2012) 2011 Erasure of spinal memory traces of pain by a brief, high-dose opioid administration. Science Ruscheweyh R, Wilder-Smith O, Drdla R, Liu X-G, Sandkühler J (2011) Long-term potentiation in spinal nociceptive pathways as a 2011 13;335(6065):235-8 Heinl C, Drdla R, Xanthos DN, Sandkühler J (2011) Distinct mechanisms underlying pronociceptive effects of opioids. J Neurosci 36 (46):16748-16756 novel target for pain therapy. Mol Pain 7:20. Gustorff B, Hauer D, Thaler J, Seis A, Draxler J (2011) Antihyperalgesic efficacy of 5% lidocaine medicated plaster in capsaicin and sunburn pain models - two randomized, double-blinded, placebo-controlled crossover trials in healthy volunteers. Expert Opin Pharmacother 12(18):2781-90. 2011 Sandkühler,J. & Gruber-Schoffnegger,D. Hyperalgesia by synaptic long-term potentiation (LTP): an update. Curr. Opin. Pharmacol. 12, 18-27 (2011). 2011 Prof. Burkhard Gustorff: Head of Department Anaesthesiology, Wilhelminenspital – Chief physician (2009) 2012 Ruth Drdla-Schutting: Assistant Professor, Medical University of Vienna, CBR (2011) Drdla-Schutting R, Benrath J, Wunderbaldinger G, Sandkühler J (2012) Erasure of spinal memory traces of pain by a brief, highdose opioid administration. Science 13;335(6065):235-8 Ortner C, Womastek I, Margeta K, Schulz M, Gustorff B (2012) Dose Response of Tramadol and its Combination with Acetaminophen in UVB induced Hyperalgesia. Eur J Pain 16(4): 562-73 2012 Sandkühler J , Lee J (2013) How to erase memory traces of pain and fear Trends Neurosci., doi: 10.1016/j.tins.2013.03.004 2013 Gustorff B, Sycha T, Lieba-Samal D, Rolke R, Treede RD, Magerl W (2013).The pattern and time course of somatosensory changes in the human UVB sunburn model reveal the presence of peripheral and central sensitization. Pain 154(4):586-97 2013 A novel role for opioids: the reversal of established hyperalgesia and chronic pain by synaptic depotentiation Jürgen Sandkühler, Ruth Drdla-Schutting, Burkhard Gustorff Thank you for your attention!