Depressive-like States Heighten the Aversion to Painful Stimuli in a Rat Model of Comorbid Chronic Pain and Depression
Depressive-like States Heighten the Aversion to Painful Stimuli in a Rat Model of Comorbid Chronic Pain and Depression
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DOI：
10.1097/aln.0b013e3182657b3e
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发表时间：
2012-09-01
期刊：
影响因子：
8.8
通讯作者：
Berrocoso, Esther
中科院分区：
文献类型：
--
作者：
Bravo, Lidia;Antonio Mico, Juan;Berrocoso, Esther
背景：慢性疼痛和抑郁是两种复杂的状态，具有感觉/躯体和情绪成分，在合并症的情况下它们可能会相互加剧，导致预后较差。方法：作者评估了大鼠模型中的感觉和情绪成分，该模型将慢性压迫性损伤（CCI，一种慢性神经病理性疼痛模型）与不可预测的慢性轻度应激（CMS，一种实验性应激）相结合。 抑郁症模型）。此外，还评估了前扣带皮层中细胞外信号调节激酶 1 和 2 的磷酸化/激活以及神经元密度。测试了四组：假对照、假 CMS、CCI 对照和 CCI-CMS。 结果：CMS 选择性地增强了接受 CCI 的动物对痛苦经历的厌恶，如在 20、25 和 30 分钟的地方逃避/回避测试中测量的那样（CCICMS（平均值 +/- SEM）：75.68 +/- 3.32、66.75 +/- 4.70、 77.54 +/- 3.60 对比 CCI 对照：分别为 44.66 +/- 6.07、43.17 +/- 6.92、52.83 +/- 5.92），同时细胞外信号调节激酶磷酸化/激活的积累增加（CCI-CMS：4.17 +/- 0.52 对比假对照：0.96 +/- 0.05）以及前扣带皮层神经元密度降低。相比之下，慢性疼痛并没有加剧 CMS 大鼠的抑郁特征（快感缺乏和行为绝望）。此外，抑郁症增强了对某些特定感觉疼痛形式的感知，例如冷异常性疼痛，但对机械阈值没有影响。结论：这些发现支持抑郁症导致慢性疼痛患者解释疼痛时情绪功能障碍的理论。此外，疼痛-抑郁的组合动物模型可能为研究疼痛和抑郁的共病提供有价值的工具。
Background: Chronic pain and depression are two complex states with sensory/somatic and emotional components, and they may mutually exacerbate one another in conditions of comorbidity, leading to a poorer prognosis.Methods: The authors have evaluated the sensory and emotional components in a rat model combining chronic constriction injury (CCI, a model of chronic neuropathic pain) with unpredictable chronic mild stress (CMS, an experimental model of depression). In addition, the phosphorylation/activation of the extracellular signal-regulated kinases 1 and 2 and neuronal density was also evaluated in the anterior cingulate cortex. Four groups were tested: sham-control, sham-CMS, CCI-control, and CCI-CMS.Results: CMS selectively heightens aversion to painful experiences in animals subjected to CCI, as measured in the place escape/avoidance test at 20, 25, and 30 min (CCICMS (mean +/- SEM): 75.68 +/- 3.32, 66.75 +/- 4.70, 77.54 +/- 3.60 vs. CCI-control: 44.66 +/- 6.07, 43.17 +/- 6.92, 52.83 +/- 5.92, respectively), in conjunction with an increase in the accumulation of phosphorylation/activation of the extracellular signal-regulated kinases (CCI-CMS: 4.17 +/- 0.52 vs. sham-control: 0.96 +/- 0.05) and a decrease in neuronal density in the anterior cingulate cortex. In contrast, chronic pain did not exacerbate the characteristic profile of depression (anhedonia and behavioral despair) in rats subjected to CMS. Furthermore, depression enhances the perception of some specific modalities of sensorial pain such as cold allodynia but has no influence on mechanical threshold.Conclusions: These findings support the theory that depression leads to emotional dysfunction in the interpretation of pain in patients suffering chronic pain. In addition, combined animal models of pain-depression may provide a valuable tool to study the comorbidity of pain and depression.