Astrocyte elimination in the lumbar enlargement attenuates neuropathic pain after spinal cord injury

Neuropathic pain after spinal cord injury (SCI) can impose heavy physical, psychological and economic burdens on patients. However, the effects of currently available treatments are limited. Previous evidence has supported the concept that astrocytes play a critical role in persistent neuropathic pain after SCI. Therefore, we explored the effect of astrocyte elimination in the spinal cord on the attenuation of neuropathic pain. In this study, we constructed a reliable mouse spinal cord contusion model of neuropathic pain and measured pain-related phenotypes with an electronic von Frey apparatus and a cold/hot plate. Immunofluorescence staining revealed that astrocyte activation was increased in the lumbar enlargement of mice with SCI-induced pain, including the three largest ascending tracts and the superficial dorsal horn (SDH). Through transgenic mice injected with an adeno-associated virus (AAV) vector and diphtheria toxin (DT), resident astrocytes in the lumbar enlargement were targeted and eliminated, and the three symptoms of neuropathic pain (mechanical allodynia, thermal hyperalgesia, and cold hyperalgesia) were attenuated. RNA sequencing analysis showed that astrocyte elimination activated the type I interferon (IFN) signalling pathway. Furthermore, we found that oligodendrocyte activation in the lumbar enlargement was decreased at one week after astrocyte elimination. Our study demonstrates that astrocyte elimination after SCI can attenuate neuropathic pain and that this pain relief may be closely associated with type I IFN signalling activation and oligodendrocyte inhibition, providing some clues for the treatment of neuropathic pain.