Neuron-restrictive silencer factor in periaqueductal gray contributes to remifentanil-induced postoperative hyperalgesia via repression of the mu-opioid receptor
Neuron-restrictive silencer factor in periaqueductal gray contributes to remifentanil-induced postoperative hyperalgesia via repression of the mu-opioid receptor
复制标题
导水管周围灰质神经元限制性沉默因子通过抑制μ阿片受体导致瑞芬太尼术后痛觉过敏
DOI：
10.1016/j.jns.2015.03.018
复制
发表时间：
2015-05-15
影响因子：
4.4
通讯作者：
Gu, Xiaoping
中科院分区：
文献类型：
--
作者：
Lu, Cui'e;Shi, Linyu;Gu, Xiaoping
背景：超短效多阿片受体（MOR）激动剂瑞芬太尼在临床前和临床研究中均可诱导术后痛觉过敏。然而，确切的机制尚不清楚，尽管阿片受体表达的变化可能是一个相关的特征。神经元限制性沉默因子（NRSF）是特定神经元细胞中MOR表达的重要调控因子。通过小鼠术后切口疼痛模型，我们评估了MOR和NRSF的表达，并研究了NRSF表达的中断是否可以预防手术切口和皮下输注瑞芬太尼引起的术后伤害性致敏。方法：分别采用足部退断机械阈值（PWMT）和足部退断热潜伏期（PWTL）评价手术和脑室注射NRSF反义寡核苷酸后的机械异常性痛和热痛觉过敏。Western blotting分析MOR和NRSF的表达水平。结果：术中输注瑞芬太尼后NRSF表达水平升高，导致肾导水管周围灰质（PAG）中MOR表达抑制。用NRSF反义寡核苷酸阻断NRSF可显著提高MOR的表达水平，减轻术中输注瑞芬太尼引起的机械性异常痛和热痛觉过敏。结论：NRSF是PAG中MOR的负调节因子，参与瑞芬太尼术后致痛觉过敏。PAG中的NRSF可能是这种疼痛治疗的潜在靶点。(C) 2015 Elsevier B.V.版权所有
Background: The ultra-short-acting mu-opioid receptor (MOR) agonist remifentanil induces postoperative hyperalgesia both in preclinical and clinical research studies. However, the precise mechanisms remain unclear, although changes in opioid receptor expression might be a correlative feature. Neuron-restrictive silencer factor (NRSF) functions as a crucial regulator of MOR expression in specific neuronal cells. Using a mouse model of incisional postoperative pain, we assessed the expression of MOR and NRSF and investigated whether disruption of NRSF expression could prevent the postoperative nociceptive sensitization induced by surgical incision and subcutaneous infusion of remifentanil.Methods: Paw withdrawal mechanical threshold (PWMT) and paw withdrawal thermal latency (PWTL) were independently used to assess mechanical allodynia and thermal hyperalgesia after surgery and cerebral ventricle injection of NRSF antisense oligonucleotide. Western blotting analyses were preformed to assess the expression levels of MOR and NRSF.Results: NRSF expression levels were enhanced after intraoperative infusion of remifentanil, resulting in repression of MOR expression in the periaqueductal gray (PAG). NRSF blockade with an NRSF antisense oligonucleotide significantly enhanced the expression levels of MOR and alleviated mechanical allodynia and thermal hyperalgesia induced by intraoperative infusion of remifentanil.Conclusion: NRSF functions as a negative regulator of MOR in PAG and contributes to remifentanil-induced postoperative hyperalgesia. NRSF in PAG may be a potential target for this pain therapy. (C) 2015 Elsevier B.V. All rights reserved.