Abstract

Inflammatory pain activates astrocytes and increases inflammatory cytokine release in the spinal cord. Mitochondrial fusion and fission rely on the functions of dynamin-related protein 1 (Drp1) and optic atrophy 1 (OPA1), which are essential for the synaptic transmission and plasticity. In the present study, we aimed to explore the effects of 2-bromopalmitate (2-BP), an inhibitor of protein palmitoylation, on the modulation of pain behavior. Rats were intraplantar injected with complete Freund’s adjuvant (CFA) to establish an inflammatory pain model. In the spinal cord of rats with CFA-induced inflammatory pain, the expression of astrocyte-specific glial fibrillary acidic protein (GFAP) and contents of proinflammatory cytokines IL-1β and TNF-α were increased. Mitochondrial Drp1 was increased, while OPA1 was decreased. Consequently, CFA induced reactive oxygen species (ROS) production and Bcl-2-associated X protein (BAX) expression. The intrathecal administration of 2-BP significantly reversed the pain behaviors of the inflammatory pain in rats. Moreover, 2-BP also reduced the Drp1 expression, elevated the OPA1 expression, and further reduced the GFAP, IL-1β, and TNF-α expression and ROS production. Furthermore, in vitro study proved a similar effect of 2-BP on the regulation of Drp1 and OPA1 expression. 2-BP also increased the mitochondrial membrane potential and decreased the levels of BAX, ROS, and proinflammatory cytokines. These results indicate that 2-BP may attenuate the inflammatory pain of CFA-treated rats via regulating mitochondrial fission/fusion balance and function.

中文翻译：

---

2-溴棕榈酸酯通过维持线粒体裂变/融合平衡和功能减轻炎症性疼痛

摘要

炎性疼痛激活星形胶质细胞并增加脊髓中炎性细胞因子的释放。线粒体融合和裂变依赖于动力相关蛋白1（Drp1）和视神经萎缩1（OPA1）的功能，这对于突触传递和可塑性至关重要。在本研究中，我们旨在探讨2-棕榈棕榈酸酯（2-BP）（一种蛋白质棕榈酰化抑制剂）对疼痛行为的调节作用。大鼠足底内注射完全弗氏佐剂（CFA）以建立炎性疼痛模型。在CFA引起的炎性疼痛的大鼠脊髓中，星形胶质细胞特异性胶质纤维酸性蛋白（GFAP）的表达以及促炎细胞因子IL-1β和TNF-α的含量增加。线粒体Drp1增加，而OPA1减少。所以，CFA诱导了活性氧（ROS）的产生和Bcl-2相关的X蛋白（BAX）的表达。鞘内注射2-BP可明显逆转大鼠炎性疼痛的疼痛行为。此外，2-BP还降低了Drp1表达，提高了OPA1表达，并进一步降低了GFAP，IL-1β和TNF-α的表达以及ROS的产生。此外，体外研究证明2-BP对Drp1和OPA1表达的调节具有相似的作用。2-BP还增加了线粒体膜电位，并降低了BAX，ROS和促炎细胞因子的水平。这些结果表明2-BP可以通过调节线粒体的裂变/融合平衡和功能减轻CFA治疗的大鼠的炎性疼痛。