Department of Biological Applications and Technology, University of Ioannina, 45110 Ioannina, Greece.
Institute of Biosciences, University Research Center of Ioannina, 45110 Ioannina, Greece.
Int J Mol Sci. 2024 Aug 24;25(17):9185. doi: 10.3390/ijms25179185.
The insular cortex is an important hub for sensory and emotional integration. It is one of the areas consistently found activated during pain. While the insular's connections to the limbic system might play a role in the aversive and emotional component of pain, its connections to the descending pain system might be involved in pain intensity coding. Here, we used anterograde tracing with viral expression of mCherry fluorescent protein, to examine the connectivity of insular axons to different brainstem nuclei involved in the descending modulation of pain in detail. We found extensive connections to the main areas of descending pain control, namely, the periaqueductal gray (PAG) and the raphe magnus (RMg). In addition, we also identified an extensive insular connection to the parabrachial nucleus (PBN). Although not as extensive, we found a consistent axonal input from the insula to different noradrenergic nuclei, the locus coeruleus (LC), the subcoereuleus (SubCD) and the A5 nucleus. These connections emphasize a prominent relation of the insula with the descending pain modulatory system, which reveals an important role of the insula in pain processing through descending pathways.
脑岛是感觉和情绪整合的重要中枢。它是在疼痛期间始终被发现激活的区域之一。虽然脑岛与边缘系统的连接可能在疼痛的厌恶和情绪成分中发挥作用，但它与下行疼痛系统的连接可能参与疼痛强度编码。在这里，我们使用病毒表达 mCherry 荧光蛋白的顺行示踪技术，详细检查了脑岛轴突与不同脑干核的连接，这些核参与下行疼痛调制。我们发现与主要的下行疼痛控制区域有广泛的连接，即导水管周围灰质（periaqueductal gray，PAG）和中缝大核（raphe magnus，RMg）。此外，我们还确定了脑岛与臂旁核（parabrachial nucleus，PBN）之间广泛的连接。虽然没有那么广泛，但我们发现脑岛对不同去甲肾上腺素能核的轴突输入是一致的，包括蓝斑（locus coeruleus，LC）、下蓝斑（subcoeruleus，SubCD）和 A5 核。这些连接强调了脑岛与下行疼痛调制系统的重要关系，揭示了脑岛通过下行途径参与疼痛处理的重要作用。
