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.
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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)
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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
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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)
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