Chronic, pathological pain remains a global health problem and a challenge to basic and clinical sciences. A major obstacle to preventing, treating or reverting chronic pain has been that the nature of neural circuits underlying the diverse components of the complex, multidimensional experience of pain is not well understood. Moreover, chronic pain involves diverse maladaptive plasticity processes, which have not been decoded mechanistically in terms of involvement of specific circuits and cause-effect relationships. This review aims to discuss recent advances in our understanding of circuit connectivity in the mammalian brain at the level of regional contributions and specific cell types in acute and chronic pain. A major focus is placed on functional dissection of sub-neocortical brain circuits using optogenetics, chemogenetics and imaging technological tools in rodent models with a view towards decoding sensory, affective and motivational-cognitive dimensions of pain. The review summarizes recent breakthroughs and insights on structure-function properties in nociceptive circuits and higher order sub-neocortical modulatory circuits involved in aversion, learning, reward and mood and their modulation by endogenous GABAergic inhibition, noradrenergic, cholinergic, dopaminergic, serotonergic and peptidergic pathways. The knowledge of neural circuits and their dynamic regulation via functional and structural plasticity will be beneficial towards designing and improving targeted therapies.

中文翻译：

---

大脑中的细胞回路及其在急性和慢性疼痛中的调节作用。

慢性病理性疼痛仍然是全球性的健康问题，也是对基础科学和临床科学的挑战。预防，治疗或逆转慢性疼痛的主要障碍是，对复杂的多维疼痛体验的不同组成部分所依据的神经回路的本质尚未完全了解。此外，慢性疼痛涉及多种适应不良的可塑性过程，就涉及特定回路和因果关系而言，尚未通过机械方式进行解码。这篇综述旨在讨论我们在急性和慢性疼痛中区域贡献水平和特定细胞类型水平上对哺乳动物大脑中电路连通性的理解的最新进展。主要研究重点是利用光遗传学对亚皮下神经回路的功能解剖，啮齿动物模型中的化学遗传学和影像学技术工具，旨在解读疼痛的感觉，情感和动机-认知维度。综述总结了在伤害性回路和涉及厌恶，学习，奖赏和情绪的高阶亚神经调节回路及其通过内源性GABA能抑制，去甲肾上腺素能，胆碱能，多巴胺能，血清素能和肽能通路的调节作用中的最新突破和见解。通过功能和结构可塑性，了解神经回路及其动态调节的知识将有助于设计和改进靶向疗法。综述总结了在伤害性回路和涉及厌恶，学习，奖赏和情绪的高阶亚神经调节回路及其通过内源性GABA能抑制，去甲肾上腺素能，胆碱能，多巴胺能，血清素能和肽能通路的调节作用中的最新突破和见解。通过功能和结构可塑性，了解神经回路及其动态调节的知识将有助于设计和改进靶向疗法。综述总结了在伤害性回路和涉及厌恶，学习，奖赏和情绪的高阶亚神经调节回路及其通过内源性GABA能抑制，去甲肾上腺素能，胆碱能，多巴胺能，血清素能和肽能通路的调节作用中的最新突破和见解。通过功能和结构可塑性，了解神经回路及其动态调节的知识将有助于设计和改进靶向疗法。