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Science 335 (6065): 235-238

Copyright © 2012 by the American Association for the Advancement of Science

Erasure of a Spinal Memory Trace of Pain by a Brief, High-Dose Opioid Administration

Ruth Drdla-Schutting, Justus Benrath,* Gabriele Wunderbaldinger, Jürgen Sandkühler{dagger}

Abstract: Painful stimuli activate nociceptive C fibers and induce synaptic long-term potentiation (LTP) at their spinal terminals. LTP at C-fiber synapses represents a cellular model for pain amplification (hyperalgesia) and for a memory trace of pain. μ-Opioid receptor agonists exert a powerful but reversible depression at C-fiber synapses that renders the continuous application of low opioid doses the gold standard in pain therapy. We discovered that brief application of a high opioid dose reversed various forms of activity-dependent LTP at C-fiber synapses. Depotentiation involved Ca2+-dependent signaling and normalization of the phosphorylation state of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors. This also reversed hyperalgesia in behaving animals. Opioids thus not only temporarily dampen pain but may also erase a spinal memory trace of pain.

Department of Neurophysiology, Center for Brain Research, Medical University of Vienna, A-1090 Vienna, Austria.

* Present address: Centre of Pain Therapy, Clinic of Anaesthesia and Intensive Care, University Medical Centre Mannheim, Medical Faculty Heidelberg University, D-68167 Mannheim, Germany.

{dagger} To whom correspondence should be addressed. E-mail: juergen.sandkuehler{at}

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