Publication Date:
2012-01-17
Description:
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. mu-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 alpha-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.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Drdla-Schutting, Ruth -- Benrath, Justus -- Wunderbaldinger, Gabriele -- Sandkuhler, Jurgen -- New York, N.Y. -- Science. 2012 Jan 13;335(6065):235-8. doi: 10.1126/science.1211726.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Neurophysiology, Center for Brain Research, Medical University of Vienna, A-1090 Vienna, Austria.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22246779" target="_blank"〉PubMed〈/a〉
Keywords:
Analgesics, Opioid/*administration & dosage
;
Animals
;
Calcium Signaling
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Evoked Potentials
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Hyperalgesia/chemically induced/drug therapy
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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
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Protein Phosphatase 1/antagonists & inhibitors/metabolism
;
Rats
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Rats, Sprague-Dawley
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Receptors, AMPA/metabolism
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Receptors, Opioid, mu/agonists/metabolism
;
Sciatic Nerve/*drug effects/physiology
;
Somatostatin/administration & dosage/analogs & derivatives
;
Spinal Cord/physiology
;
Synapses/*drug effects/physiology
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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