Persistent pain alters AMPA receptor subunit levels in the nucleus accumbens.
Persistent pain alters AMPA receptor subunit levels in the nucleus accumbens.
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持续疼痛会改变伏隔核中的 AMPA 受体亚基水平。
DOI：
10.1186/s13041-015-0140-z
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发表时间：
2015-08-12
期刊：
影响因子：
3.6
通讯作者：
Wang J
中科院分区：
文献类型：
--
作者：
Su C;D'amour J;Lee M;Lin HY;Manders T;Xu D;Eberle SE;Goffer Y;Zou AH;Rahman M;Ziff E;Froemke RC;Huang D;Wang J
临床研究发现，各种疼痛状况与抑郁情绪有关。在持续性或慢性疼痛的动物模型中也描述了类似抑郁的行为。在啮齿动物慢性神经病理性疼痛模型中，伏隔核(NAC)中α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic酸的GluA1亚单位(AMPA)受体水平的升高被发现可以抑制抑郁症状。然而，在动物模型中，可逆性术后疼痛或炎性疼痛对抑郁等情感行为的影响尚未得到很好的表征。也不知道在不同的疼痛条件下，需要多长时间才能引起NAC中AMPA受体亚单位的变化。在这项研究中，我们比较了三种疼痛模型的行为和生化变化：用于术后疼痛的爪状切开(PI)模型，用于持续性但可逆炎性疼痛的完全弗氏佐剂(CFA)模型，以及用于慢性术后神经病理性疼痛的备用神经损伤(SNI)模型。在所有三种模型中，大鼠都出现了抑郁症状，同时出现感觉异常痛觉。然而，在这三种模型中，NAC突触的GluA1水平不同。在PI模型中，NAC突触AMPA型受体的GluA1亚单位的水平没有改变。在CFA模型中，持续疼痛一段时间(7d)后，GluA1水平升高，导致缺乏GluA2的AMPA受体的形成。然而，随着疼痛症状开始缓解，GluA1水平恢复到基线水平。与此同时，在疼痛持续超过14天的SNI模型中，GluA1水平在疼痛变得持续并保持高水平后开始上升。此外，我们发现，阻断NAC中缺乏GluA2的AMPA受体只在持续性疼痛模型中进一步减轻抑郁症状。我们的研究表明，虽然短期和持续性疼痛都可以触发抑郁样行为，但NAC中GluA1的上调可能代表了一种独特的适应性反应，以最大限度地减少持续性疼痛状态下的抑郁症状。
A variety of pain conditions have been found to be associated with depressed mood in clinical studies. Depression-like behaviors have also been described in animal models of persistent or chronic pain. In rodent chronic neuropathic pain models, elevated levels of GluA1 subunits of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors in the nucleus accumbens (NAc) have been found to inhibit depressive symptoms. However, the effect of reversible post-surgical pain or inflammatory pain on affective behaviors such as depression has not been well characterized in animal models. Neither is it known what time frame is required to elicit AMPA receptor subunit changes in the NAc in various pain conditions. In this study, we compared behavioral and biochemical changes in three pain models: the paw incision (PI) model for post-incisional pain, the Complete Freund’s Adjuvant (CFA) model for persistent but reversible inflammatory pain, and the spared nerve injury (SNI) model for chronic postoperative neuropathic pain. In all three models, rats developed depressive symptoms that were concurrent with the presentation of sensory allodynia. GluA1 levels at the synapses of the NAc, however, differed in these three models. The level of GluA1 subunits of AMPA-type receptors at NAc synapses was not altered in the PI model. GluA1 levels were elevated in the CFA model after a period (7 d) of persistent pain, leading to the formation of GluA2-lacking AMPA receptors. As pain symptoms began to resolve, however, GluA1 levels returned to baseline. Meanwhile, in the SNI model, in which pain persisted beyond 14 days, GluA1 levels began to rise after pain became persistent and remained elevated. In addition, we found that blocking GluA2-lacking AMPA receptors in the NAc further decreased the depressive symptoms only in persistent pain models. Our study shows that while both short-term and persistent pain can trigger depression-like behaviors, GluA1 upregulation in the NAc likely represents a unique adaptive response to minimize depressive symptoms in persistent pain states.