Department of Neurophysiology, Center for Brain Research, Medical University of Vienna, A-1090 Vienna, Austria.
Science. 2012 Jan 13;335(6065):235-8. doi: 10.1126/science.1211726.
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.
疼痛刺激激活伤害性 C 纤维，并在其脊髓末端诱导突触长时程增强（LTP）。C 纤维突触的 LTP 代表了疼痛放大（痛觉过敏）和疼痛记忆痕迹的细胞模型。μ-阿片受体激动剂在 C 纤维突触上产生强大但可逆的抑制作用，使得持续应用低剂量阿片类药物成为疼痛治疗的金标准。我们发现，高阿片类药物剂量的短暂应用可逆转 C 纤维突触的各种形式的活性依赖性 LTP。去敏化涉及 Ca2+依赖性信号转导和 α-氨基-3-羟基-5-甲基-4-异恶唑丙酸受体磷酸化状态的正常化。这也逆转了行为动物的痛觉过敏。因此，阿片类药物不仅可以暂时抑制疼痛，还可以消除脊髓对疼痛的记忆痕迹。
