分泌到枕三叉神经核尾部（SP5C）的炎症细胞因子可能增强炎症反应并引起颞下颌关节紊乱（TMD）相关的疼痛。我们通过两步法将三苯基膦（TPP）附着在负载钌（Ru）纳米酶的立方体脂质体金属有机骨架（MOF）表面。此设计针对线粒体，被命名为Mito-Ru MOF。该结构清除自由基和活性氧（ROS）并减轻氧化应激。本研究旨在调查Mito-Ru MOF改善TMD疼痛的效果和机制。完全弗氏佐剂（CFA）在三叉神经刷新皮肤区域中向颞下颌关节（TMJ）注射可以诱导炎症性疼痛最少持续10天。肿瘤坏死因子-α（TNF-α）、核因子κ-B（NF-κB）、长非编码RNA核泪滴组装转录本1（lncRNA NEAT1）和ROS也被证明在TMD小鼠的SP5C中被显著上调。此外，单次Mito-Ru MOF处理可以缓解TMD疼痛3天，并降低TNF-α、NF-κB、lncRNA NEAT1和ROS的表达。在TMD小鼠中，NF-κB沉默可以下调NEAT1的表达。因此，Mito-Ru MOF通过TNF-α/NF-κB/NEAT1通路抑制了ROS的产生并缓解了CFA诱导的TMD疼痛。因此，Mito-Ru MOF能有效治疗与严重急性炎症反应相关的TMD和其他疾病的疼痛。

Inflammatory cytokines that are secreted into the spinal trigeminal nucleus caudalis (Sp5C) may augment inflammation and cause pain associated with temporomandibular joint disorders (TMD). In a two-step process, we attached triphenylphosphonium (TPP) to the surface of a cubic liposome metal-organic framework (MOF) loaded with ruthenium (Ru) nanozyme. The design targeted mitochondria and was designated Mito-Ru MOF. This structure scavenges free radicals and reactive oxygen species (ROS) and alleviates oxidative stress. The present study aimed to investigate the effects and mechanisms by which Mito-Ru MOF ameliorates TMD pain. Intra-temporomandibular joint (TMJ) injections of complete Freund's adjuvant (CFA) induced inflammatory pain for ≥10 d in the skin areas innervated by the trigeminal nerve. Tumor necrosis factor-alpha (TNF-α), nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), long non-coding RNA nuclear paraspeckle assembly transcript 1 (lncRNA NEAT1), and ROS also have been proved to be significantly upregulated in the Sp5C of TMD mice. Moreover, a single Mito-Ru MOF treatment alleviated TMD pain for 3 d and downregulated TNF-α, NF-κB, lncRNA NEAT1, and ROS. NF-κB knockdown downregulated NEAT1 in the TMD mice. Hence, Mito-Ru MOF inhibited the production of ROS and alleviated CFA-induced TMD pain via the TNF-α/NF-κB/NEAT1 pathway. Therefore, Mito-Ru MOF could effectively treat the pain related to TMD and other conditions associated with severe acute inflammatory activation.