Pain Research Center, Department of Anesthesiology, University of Cincinnati Medical Center, Cincinnati, OH, USA.
Pain Research Center, Department of Anesthesiology, University of Cincinnati Medical Center, Cincinnati, OH, USA; Department of Physiology, Gachon Pain Center, Gachon University College of Medicine, Incheon, South Korea.
Brain Behav Immun. 2024 Mar;117:51-65. doi: 10.1016/j.bbi.2024.01.003. Epub 2024 Jan 6.
Microglia, resident immune cells in the central nervous system, play a role in neuroinflammation and the development of neuropathic pain. We found that the stimulator of interferon genes (STING) is predominantly expressed in spinal microglia and upregulated after peripheral nerve injury. However, mechanical allodynia, as a marker of neuropathic pain following peripheral nerve injury, did not require microglial STING expression. In contrast, STING activation by specific agonists (ADU-S100, 35 nmol) significantly alleviated neuropathic pain in male mice, but not female mice. STING activation in female mice leads to increase in proinflammatory cytokines that may counteract the analgesic effect of ADU-S100. Microglial STING expression and type I interferon-ß (IFN-ß) signaling were required for the analgesic effects of STING agonists in male mice. Mechanistically, downstream activation of TANK-binding kinase 1 (TBK1) and the production of IFN-ß, may partly account for the analgesic effect observed. These findings suggest that STING activation in spinal microglia could be a potential therapeutic intervention for neuropathic pain, particularly in males.
小胶质细胞是中枢神经系统中的固有免疫细胞，在神经炎症和神经性疼痛的发展中发挥作用。我们发现干扰素基因刺激物（STING）主要表达于脊髓小胶质细胞，并在外周神经损伤后上调。然而，外周神经损伤后作为神经性疼痛标志物的机械性痛觉过敏并不需要小胶质细胞 STING 表达。相比之下，特异性激动剂（ADU-S100，35nmol）激活 STING 显著缓解雄性小鼠的神经性疼痛，但对雌性小鼠无效。雌性小鼠中 STING 的激活导致促炎细胞因子增加，可能抵消 ADU-S100 的镇痛作用。小胶质细胞 STING 表达和 I 型干扰素-β（IFN-β）信号传导是雄性小鼠中 STING 激动剂镇痛作用所必需的。从机制上讲，TANK 结合激酶 1（TBK1）的下游激活和 IFN-β的产生可能部分解释了观察到的镇痛作用。这些发现表明，脊髓小胶质细胞中 STING 的激活可能成为治疗神经性疼痛的一种潜在治疗干预手段，尤其是在男性中。
