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：

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2-溴棕榈酸酯通过维持线粒体裂变/融合平衡和功能来减轻炎症疼痛

 抽象的

炎性疼痛会激活星形胶质细胞并增加脊髓中炎性细胞因子的释放。线粒体融合和分裂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，我们旨在探讨蛋白质棕榈酰化抑制剂 2-溴棕榈酸酯 (2-BP) 对疼痛行为调节的影响。给大鼠足底注射完全弗氏佐剂（CFA）建立炎性疼痛模型。在CFA诱导的炎性痛大鼠脊髓中，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。因此，CFA 诱导活性氧 (ROS) 产生和 Bcl-2 相关 X 蛋白 (BAX) 表达。鞘内注射2-BP可显着逆转大鼠炎性痛的疼痛行为。此外，2-BP还降低了Drp1的表达，升高了OPA1的表达，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表达的调节具有类似的作用。 2-BP 还增加线粒体膜电位并降低 BAX、ROS 和促炎细胞因子的水平。这些结果表明，2-BP 可能通过调节线粒体裂变/融合平衡和功能来减轻 CFA 治疗大鼠的炎性疼痛。