Electroacupuncture promotes functional recovery after spinal cord injury in rats by regulating P2X4R/p38 MAPK signaling pathway and suppressing inflammatory responses

This study aimed to investigate whether electroacupuncture can modulate the purinergic P2X4 receptor (P2X4R)/p38 mitogen-activated protein kinase (MAPK) pathway, thereby reducing inflammatory responses and facilitating functional recovery in a rat model of spinal cord injury (SCI). The SCI model was developed in female rats. The electroacupuncture intervention began on the seventh day after modeling, mainly Jiaji, Dazhui, and Mingmen. Sensory function was evaluated via the mechanical withdrawal threshold (MWT) and thermal withdrawal latency (TWL), while motor function was measured using the Basso, Beattie, and Bresnahan (BBB) scoring system and footprint analysis. To analyze the protein expression related to the P2X4R/p38 MAPK signaling pathways, methods such as immunohistochemistry, immunofluorescence analysis, quantitative real-time PCR, and western blotting were utilized. To evaluate the levels of inflammatory cytokines, ELISAs were utilized. Additionally, after hematoxylin and eosin staining, histological alterations in spinal cord tissue were investigated. The results showed that MWT, TWL, and BBB scores were decreased, while P2X4R, phosphorylated-p38 MAPK, and phosphorylated nuclear factor κB p65 expression levels were increased, tumor necrosis factor-α, interleukin (IL)-1β, and IL-6 levels were elevated, and histopathological damage was more pronounced after SCI. However, electroacupuncture treatment effectively reversed these pathological changes. We demonstrate that electroacupuncture can alleviate SCI in rats by inhibiting the activation of the P2X4R/p38 MAPK pathway and reducing inflammatory response.