Chemogenetic Silencing of the Locus Coeruleus-Basolateral Amygdala Pathway Abolishes Pain-Induced Anxiety and Enhanced Aversive Learning in Rats
Chemogenetic Silencing of the Locus Coeruleus-Basolateral Amygdala Pathway Abolishes Pain-Induced Anxiety and Enhanced Aversive Learning in Rats
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DOI：
10.1016/j.biopsych.2019.02.018
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发表时间：
2019-06-15
影响因子：
10.6
通讯作者：
Berrocoso, Esther
中科院分区：
文献类型：
--
作者：
Llorca-Torralba, Meritxell;Suarez-Pereira, Irene;Berrocoso, Esther
背景：疼痛影响感觉和情绪厌恶反应，慢性时常引起焦虑相关疾病。然而，焦虑和慢性pain.METHODS之间的相互作用的神经机制仍然不清楚：我们的特点是在大鼠模型的感觉，情绪和认知神经性疼痛（慢性压迫性损伤）的后果。此外，我们确定了蓝斑（LC）神经元的作用，项目的基底外侧杏仁核（BLA）使用DREADD（设计师受体专门激活的设计师药物）。结果：慢性压迫性损伤导致感觉超敏反应在短期和长期。否则，长期疼痛导致焦虑样的个人资料（在高架零迷宫和开放领域的测试），以及增加的反应学习厌恶的情况下（在被动回避和恐惧条件反射测试）和非情绪认知任务的损害（在新的对象识别和对象模式的分离测试）。LC-BLA通路的化学发生阻断和β-肾上腺素能受体的BLA内或全身拮抗作用消除了长期疼痛诱导的焦虑和增强的恐惧学习。相比之下，该通路的化学发生激活诱导焦虑样行为，并增强了假手术动物的厌恶性学习和记忆指数，尽管它对短期和长期慢性压迫性损伤动物几乎没有影响。有趣的是，调制的LC-BLA活动没有修改感觉知觉或情节memory.CONCLUSIONS：我们的研究结果表明，尺寸与疼痛的处理独立的途径，并有一个过度激活的LC-BLA通路时，焦虑和慢性疼痛共病，这涉及β-肾上腺素能受体的活动。
BACKGROUND: Pain affects both sensory and emotional aversive responses, often provoking anxiety-related diseases when chronic. However, the neural mechanisms underlying the interactions between anxiety and chronic pain remain unclear.METHODS: We characterized the sensory, emotional, and cognitive consequences of neuropathic pain (chronic constriction injury) in a rat model. Moreover, we determined the role of the locus coeruleus (LC) neurons that project to the basolateral amygdala (BLA) using a DREADD (designer receptor exclusively activated by designer drugs).RESULTS: Chronic constriction injury led to sensorial hypersensitivity in both the short term and long term. Otherwise, long-term pain led to an anxiety-like profile (in the elevated zero maze and open field tests), as well as increased responses to learn aversive situations (in the passive avoidance and fear conditioning tests) and an impairment of nonemotional cognitive tasks (in the novel object recognition and object pattern of separation tests). Chemogenetic blockade of the LC-BLA pathway and intra-BLA or systemic antagonism of beta-adrenergic receptors abolished both long-term pain-induced anxiety and enhanced fear learning. By contrast, chemogenetic activation of this pathway induced anxiety-like behaviors and enhanced the aversive learning and memory index in sham animals, although it had little effect on short- and long-term chronic constriction injury animals. Interestingly, modulation of LC-BLA activity did not modify sensorial perception or episodic memory.CONCLUSIONS: Our results indicate that dimensions associated with pain are processed by independent pathways and that there is an overactivation of the LC-BLA pathway when anxiety and chronic pain are comorbid, which involves the activity of beta-adrenergic receptors.