Preoperative Pain Facilitates Postoperative Cognitive Dysfunction via Periaqueductal Gray Matter–Dorsal Raphe Circuit
Preoperative Pain Facilitates Postoperative Cognitive Dysfunction via Periaqueductal Gray Matter–Dorsal Raphe Circuit
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DOI：
10.1016/j.neuroscience.2023.03.019
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发表时间：
2023-03
期刊：
影响因子：
3.3
通讯作者：
Haoyue Deng;Yi Wu;Po Gao;Dexu Kong;Chao Pan;Saihong Xu;Dan Tang;Yingfu Jiao;Da-xiang Wen-Da-xiang-We
中科院分区：
文献类型：
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作者：
Haoyue Deng;Yi Wu;Po Gao;Dexu Kong;Chao Pan;Saihong Xu;Dan Tang;Yingfu Jiao;Da-xiang Wen-Da-xiang-We
术后认知功能障碍（Postoperative cognitive dysfunction，POCD）是一种由药物引起的术后快速发生的疾病，尤其是老年患者，其恢复困难，严重威胁患者的生活质量，因此识别POCD的危险因素并进行早期干预对预防POCD的发生具有重要意义。众所周知，疼痛会损害认知功能，许多手术患者在术前会经历不同程度的疼痛，但这些患者是否易患POCD仍是未知数。在此，我们发现在大鼠后爪注射完全弗氏佐剂（CFA）诱导的慢性疼痛（7天，而不是1天急性疼痛）在暴露于七氟烷麻醉后容易诱导空间认知和记忆障碍。其次，在痛觉机制方面，我们着重研究了中脑导水管周围灰质（PAG），这是一个在痛觉过程中起关键作用的核团。应用病毒示踪和膜片钳技术，观察到大鼠PAG腹外侧区（vlPAG）向邻近的中缝背核（DR）的神经投射，即整个大脑的多巴胺能投射的起源。免疫荧光染色和western blot结果显示，CFA处理7 d和七氟醚处理3 h后，大鼠DR合成5-羟色胺的色氨酸羟化酶2（Tryptophan Hydroxylase 2，TPH 2）显著增加，而vlPAG-DR投射的化学遗传学抑制导致明显的空间学习记忆障碍。我们的研究表明，术前慢性疼痛可能会促进通过PAG-DR神经回路接受麻醉后的认知功能障碍，预防性镇痛应是降低POCD发生率的重要措施。
Postoperative cognitive dysfunction (POCD) is a medically induced, rapidly occurring postoperative disease, which is hard to recover and seriously threatens the quality of life, especially for elderly patients, so it is important to identify the risk factors for POCD and apply early intervention to prevent POCD. As we have known, pain can impair cognition, and many surgery patients experience different preoperative pain, but it is still unknown whether these patients are vulnerable for POCD. Here we found that chronic pain (7 days, but not 1 day acute pain) induced by Complete Freund’s Adjuvant (CFA) injected in the hind paw of rats could easily induce spatial cognition and memory impairment after being exposed to sevoflurane anesthesia. Next, for the mechanisms, we focused on the Periaqueductal Gray Matter (PAG), a well-known pivotal nucleus in pain process. It was detected the existence of neural projection from ventrolateral PAG (vlPAG) to adjacent nucleus Dorsal Raphe (DR), the origin of serotonergic projection for the whole cerebrum, through virus tracing and patch clamp recordings. The Immunofluorescence staining and western blot results showed that Tryptophan Hydroxylase 2 (TPH2) for serotonin synthesis in the DR was increased significantly in the rats treated with CFA for 7 days and sevoflurane for 3 hours, while chemo-genetic inhibition of the vlPAG-DR projection induced obvious spatial learning and memory impairment. Our study suggests that preoperative chronic pain may facilitate cognitive function impairment after receiving anesthesia through the PAG-DR neural circuit, and preventative analgesia should be a considerable measure to reduce the incidence of POCD.