Erasure of a spinal memory trace of pain by a brief, high-dose opioid administration.

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 Ca(2+)-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.

• Authors: Ruth Drdla-Schutting, Justus Benrath, Gabriele Wunderbaldinger, Jürgen Sandkühler
• Journal: Science (New York, N.Y.) (Science) Vol. 335 Issue 6065 Pg. 235-8 (Jan 13 2012) ISSN: 1095-9203 [Electronic] United States
• PMID: 22246779 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Analgesics, Opioid
• Piperidines
• Receptors, AMPA
• Receptors, Opioid, mu
• phenylalanyl-cyclo(cysteinyltyrosyl-tryptophyl-ornithyl-threonyl-penicillamine)threoninamide
• Naloxone
• Somatostatin
• Protein Kinase C
• protein kinase M zeta, rat
• Protein Phosphatase 1
• Remifentanil
• glutamate receptor ionotropic, AMPA 2
• glutamate receptor ionotropic, AMPA 1

Topics

• Analgesics, Opioid (administration & dosage)
• Animals
• Calcium Signaling
• Evoked Potentials
• Hyperalgesia (chemically induced, drug therapy)
• Long-Term Potentiation (drug effects)
• Male
• Naloxone (administration & dosage)
• Nerve Fibers, Unmyelinated (drug effects, physiology)
• Nociceptive Pain (drug therapy, physiopathology)
• Phosphorylation
• Piperidines (administration & dosage)
• Protein Kinase C (antagonists & inhibitors, metabolism)
• Protein Phosphatase 1 (antagonists & inhibitors, metabolism)
• Rats
• Rats, Sprague-Dawley
• Receptors, AMPA (metabolism)
• Receptors, Opioid, mu (agonists, metabolism)
• Remifentanil
• Sciatic Nerve (drug effects, physiology)
• Somatostatin (administration & dosage, analogs & derivatives)
• Spinal Cord (physiology)
• Synapses (drug effects, physiology)