title: 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.affiliation: Department of Neurophysiology, Center for Brain Research, Medical University of Vienna, A-1090 Vienna, Austria.
authors.forename: Ruth
authors.initials: R
authors.lastname: Drdla-Schutting
authors.forename: Justus
authors.initials: J
authors.lastname: Benrath
authors.forename: Gabriele
authors.initials: G
authors.lastname: Wunderbaldinger
authors.forename: Jürgen
authors.initials: J
authors.lastname: Sandkühler
mesh_terms: D000701:Analgesics, Opioid / Q000008:administration & dosage*; D000818:Animals; D020013:Calcium Signaling; D005071:Evoked Potentials; D006930:Hyperalgesia / Q000139:chemically induced / Q000188:drug therapy; D017774:Long-Term Potentiation / Q000187:drug effects*; D008297:Male; D009270:Naloxone / Q000008:administration & dosage; D036421:Nerve Fibers, Unmyelinated / Q000187:drug effects* / Q000502:physiology; D059226:Nociceptive Pain / Q000188:drug therapy* / Q000503:physiopathology; D010766:Phosphorylation; D010880:Piperidines / Q000008:administration & dosage*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism; D054645:Protein Phosphatase 1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000378:metabolism; D017450:Receptors, Opioid, mu / Q000819:agonists / Q000378:metabolism; D000077208:Remifentanil; D012584:Sciatic Nerve / Q000187:drug effects* / Q000502:physiology; D013004:Somatostatin / Q000008:administration & dosage / Q000031:analogs & derivatives; D013116:Spinal Cord / Q000502:physiology; D013569:Synapses / Q000187:drug effects* / Q000502:physiology
chemical_list: D000701:Analgesics, Opioid; D009270:Naloxone; D010880:Piperidines; D011493:Protein Kinase C; D054645:Protein Phosphatase 1; D018091:Receptors, AMPA; D017450:Receptors, Opioid, mu; D000077208:Remifentanil; D013004:Somatostatin; C049352:phenylalanyl-cyclo(cysteinyltyrosyl-tryptophyl-ornithyl-threonyl-penicillamine)threoninamide; C504730:protein kinase M zeta, rat; C104722:glutamate receptor ionotropic, AMPA 2