Department of Neurology, Renmin Hospital of Wuhan University, Wuhan 430060, Hubei Province, China.
Department of Neurology, Renmin Hospital of Wuhan University, Wuhan 430060, Hubei Province, China.
Neuroscience. 2020 Dec 15;451:207-215. doi: 10.1016/j.neuroscience.2020.10.019. Epub 2020 Oct 31.
Interleukin-18 (IL-18) is an important regulator of innate and immune responses, and is involved in the pain process, including neuropathic and cancer pain. The current study demonstrated that inflammatory soup (IS) dural infusions elicited the activation of microglia and astrocytes. In comparison, IS dural infusions induced the upregulation of IL-18 and IL-18R in microglia and astrocytes, respectively. Blocking the IL-18 signaling pathway attenuated nociceptive behavior. In comparison, blocking IL-18 signaling also suppressed the activation of astrocytes and nuclear factor-kappa B (NF-κB). IL-18 dural infusions induced nociceptive behavior and glia activation. IL-18 is a product of the activation of microglial toll-like receptor 4 (TLR4), and it acted on IL-18R expressed in astrocytes. Subsequently, it stimulated the activation of nuclear factor-kappa B (NF-κB), leading to the activation of astrocytes. In conclusion, IL-18-mediated microglia/astrocyte interactions in the medullary dorsal horn likely contribute to the development of hyperpathia or allodynia induced by migraines.
白细胞介素-18（IL-18）是先天和免疫反应的重要调节剂，参与疼痛过程，包括神经病理性和癌性疼痛。本研究表明，炎性汤（IS）硬膜内输注可激活小胶质细胞和星形胶质细胞。相比之下，IS 硬膜内输注分别诱导小胶质细胞和星形胶质细胞中 IL-18 和 IL-18R 的上调。阻断 IL-18 信号通路可减轻痛觉行为。相比之下，阻断 IL-18 信号也抑制了星形胶质细胞和核因子-κB（NF-κB）的激活。IL-18 硬膜内输注诱导痛觉行为和神经胶质细胞激活。IL-18 是小胶质细胞 Toll 样受体 4（TLR4）激活的产物，它作用于星形胶质细胞中表达的 IL-18R。随后，它刺激核因子-κB（NF-κB）的激活，导致星形胶质细胞的激活。总之，髓质背角中 IL-18 介导的小胶质细胞/星形胶质细胞相互作用可能导致偏头痛引起的痛觉过敏或痛觉过敏的发展。
