Chronic Pain Leads to Concomitant Noradrenergic Impairment and Mood Disorders
Chronic Pain Leads to Concomitant Noradrenergic Impairment and Mood Disorders
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DOI：
10.1016/j.biopsych.2012.06.033
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发表时间：
2013-01-01
影响因子：
10.6
通讯作者：
Berrocoso, Esther
中科院分区：
文献类型：
--
作者：
Alba-Delgado, Cristina;Llorca-Torralba, Meritxell;Berrocoso, Esther
研究背景：慢性疼痛患者存在以持续情绪低落和焦虑为特征的长期情绪障碍的高风险。我们提出，这可能是与蓝斑和前额皮质相关的去肾上腺素能回路功能损伤的结果，在那里情绪和感觉疼痛过程重叠。方法：我们使用坐骨神经慢性收缩损伤作为雄性Sprague-Dawley大鼠的神经性疼痛模型来评估可能诱发情绪障碍的时间依赖性变化（损伤后2、7、14和28天）。这是通过行为、电生理、微透析、免疫组织化学和Western blot检测的组合来测量的。结果：正如预期的那样，神经损伤在测试期间产生了早期和稳定的感觉疼痛阈值下降。相比之下，长期神经性疼痛（受伤后28天）导致无法应对紧张情况，引发抑郁和焦虑样行为，甚至比与疼痛感知相关的厌恶更强烈。这些行为改变的开始与去甲肾上腺素能功能障碍的中断相吻合，明显表现为：LC破裂活动增加；酪氨酸羟化酶和去甲肾上腺素转运蛋白的表达；α 2-肾上腺素受体在LC中的表达和敏感性增强。结论：长期神经性疼痛导致焦虑-抑郁样行为，这种行为比对痛苦经历的厌恶更为主要。这些变化与抑郁症的去甲肾上腺素能系统损伤一致。
Background: Patients suffering chronic pain are at high risk of suffering long-lasting emotional disturbances characterized by persistent low mood and anxiety. We propose that this might be the result of a functional impairment in noradrenergic circuits associated with locus coeruleus (LC) and prefrontal cortex, where emotional and sensorial pain processes overlap.Methods: We used a chronic constriction injury of sciatic nerve as a model of neuropathic pain in male Sprague-Dawley rats to assess the time-dependent changes that might potentially precipitate mood disorders (2, 7, 14, and 28 days after injury). This was measured through a combination of behavioral, electrophysiological, microdialysis, immunohistochemical, and Western blot assays.Results: As expected, nerve injury produced an early and stable decrease in sensorial pain threshold over the testing period. By contrast, long-term neuropathic pain (28 days after injury) resulted in an inability to cope with stressful situations, provoking depressive and anxiogenic-like behaviors, even more intense than the aversiveness associated with pain perception. The onset of these behavioral changes coincided with irruption of noradrenergic dysfunction, evident as: an increase in LC bursting activity; in tyrosine hydroxylase expression and that of the noradrenaline transporter; and enhanced expression and sensitivity of alpha 2-adrenoceptors in the LC.Conclusions: Long-term neuropathic pain leads to anxio-depressive-like behaviors that are more predominant than the aversion of a painful experience. These changes are consistent with the impairment of noradrenergic system described in depressive disorders.