2012
DOI: 10.1126/science.1211726
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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 a… Show more

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Cited by 90 publications
(73 citation statements)
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“…Compared to single-unit recording from individual neurons, measuring C-LFP is a high-throughput approach for examining the broad and net spinal nociceptive transmission in vivo. 18,48 We showed for the first time that epidural SCS inhibits C-LFP through activation of CB1 receptors in rats after nerve injury. CB1 receptors are densely expressed on the central terminals of primary afferent neurons and on postsynaptic neurons in the spinal cord.…”
Section: Discussionmentioning
confidence: 91%
“…Compared to single-unit recording from individual neurons, measuring C-LFP is a high-throughput approach for examining the broad and net spinal nociceptive transmission in vivo. 18,48 We showed for the first time that epidural SCS inhibits C-LFP through activation of CB1 receptors in rats after nerve injury. CB1 receptors are densely expressed on the central terminals of primary afferent neurons and on postsynaptic neurons in the spinal cord.…”
Section: Discussionmentioning
confidence: 91%
“…Although these data are the first, to the best of our knowledge, to show OP-LTD in striatum, OP-LTD has been described at excitatory synapses in hypothalamus 14 and inhibitory synapses in hypothalamus 17 and hippocampus 16 , mediated by KOPrs, MOPrs and DOPrs, respectively. Opioids have also been shown to modulate the induction or expression of both LTD and long-term potentiation 12,13,30–32 . In addition, transient or reversible suppression of excitatory transmission by opioid receptor signaling has been reported in other brain areas, including the nucleus accumbens 33 .…”
Section: Discussionmentioning
confidence: 99%
“…However, they are associated with some common, undesired adverse effects such as nausea, vomiting, drowsiness, urinary retention, and constipation, and in large doses may lead to respiratory depression. Moreover, recent studies indicate that opioids per se may amplify acute pain and in some cases may result in the long-term potentiation of nociceptive pathways (i.e., opioid-induced hyperalgesia, OIH) [2].…”
Section: Introductionmentioning
confidence: 99%