I am a
Home I AM A Search Login

Papers of the Week


Papers: 11 Jan 2025 - 17 Jan 2025


2024 Dec


Acta Pharm Sin B


39807339


14


12

Spinal astrocyte-derived interleukin-17A promotes pain hypersensitivity in bone cancer mice.

Authors

Liu H, Lv X, Zhao X, Yi L, Lv N, Xu W, Zhang Y

Abstract

Spinal microglia and astrocytes are both involved in neuropathic and inflammatory pain, which may display sexual dimorphism. Here, we demonstrate that the sustained activation of spinal astrocytes and astrocyte-derived interleukin (IL)-17A promotes the progression of mouse bone cancer pain without sex differences. Chemogenetic or pharmacological inhibition of spinal astrocytes effectively ameliorates bone cancer-induced pain-like behaviors. In contrast, chemogenetic or optogenetic activation of spinal astrocytes triggers pain hypersensitivity, implying that bone cancer-induced astrocytic activation is involved in the development of bone cancer pain. IL-17A expression predominantly in spinal astrocytes, whereas its receptor IL-17 receptor A (IL-17RA) was mainly detected in neurons expressing VGLUT2 and PAX2, and a few in astrocytes expressing GFAP. Specific knockdown of IL-17A in spinal astrocytes blocked and delayed the development of bone cancer pain. IL-17A overexpression in spinal astrocytes directly induced thermal hyperalgesia and mechanical allodynia, which could be rescued by CaMKII inhibitor. Moreover, selective knockdown IL-17RA in spinal or neurons, but not in astrocytes, significantly blocked the bone cancer-induced hyperalgesia. Together, our findings provide evidence for the crucial role of sex-independent astrocytic signaling in bone cancer pain. Targeting spinal astrocytes and IL-17A/IL-17RA-CaMKII signaling may offer new gender-inclusive therapeutic strategies for managing bone cancer pain.