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!