Lab for Clinical and Integrative Neuroscience, Trinity College Institute for Neuroscience, School of Psychology, Trinity College Dublin, D02 PN40 Dublin, Ireland.
Compass Physio, A83 YW96 Enfield, Ireland.
Int J Mol Sci. 2024 Aug 8;25(16):8636. doi: 10.3390/ijms25168636.
Pain perception is the consequence of a complex interplay between activation and inhibition. Noradrenergic pain modulation inhibits nociceptive transmission and pain perception. The main source of norepinephrine (NE) in the central nervous system is the Locus Coeruleus (LC), a small but complex cluster of cells in the pons. The aim of this study is to review the literature on the LC-NE inhibitory system, its influence on chronic pain pathways and its frequent comorbidities. The literature research showed that pain perception is the consequence of nociceptive and environmental processing and is modulated by the LC-NE system. If perpetuated in time, nociceptive inputs can generate neuroplastic changes in the central nervous system that reduce the inhibitory effects of the LC-NE complex and facilitate the development of chronic pain and frequent comorbidities, such as anxiety, depression or sleeping disturbances. The exact mechanisms involved in the LC functional shift remain unknown, but there is some evidence that they occur through plastic changes in the medial and lateral pathways and their brain projections. Additionally, there are other influencing factors, like developmental issues, neuroinflammatory glial changes, NE receptor affinity and changes in LC neuronal firing rates.
疼痛感知是激活和抑制之间复杂相互作用的结果。去甲肾上腺素能疼痛调制抑制伤害性传递和疼痛感知。中枢神经系统中去甲肾上腺素 (NE) 的主要来源是蓝斑 (LC)，这是桥脑中一个小而复杂的细胞群。本研究旨在综述 LC-NE 抑制系统及其对慢性疼痛途径及其常见合并症的影响。文献研究表明，疼痛感知是伤害性和环境处理的结果，并受 LC-NE 系统的调节。如果持续时间过长，伤害性输入会导致中枢神经系统的神经可塑性变化，从而降低 LC-NE 复合物的抑制作用，并促进慢性疼痛和常见合并症（如焦虑、抑郁或睡眠障碍）的发展。LC 功能转移中涉及的确切机制尚不清楚，但有一些证据表明它们通过内侧和外侧通路及其大脑投射的可塑性变化发生。此外，还有其他影响因素，如发育问题、神经炎性神经胶质变化、NE 受体亲和力和 LC 神经元放电率的变化。
