Presentation Ruth Drdla
Download
Report
Transcript Presentation Ruth Drdla
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!