Needle-Knife Therapy Relieves Inflammation and Neuronal Apoptosis in Cervical Spondylotic Radiculopathy via IRE1α-XBP1 Signaling

Study Design Translational animal study. Objective To investigate the therapeutic effects of needle-knife therapy in cervical spondylotic radiculopathy (CSR) rat models. This study also aims to determine whether these effects are mediated via inositol-requiring enzyme 1 alpha (IRE1α)-X-box binding protein 1 (XBP1) axis. Methods A CSR rat model was established via spinal canal insertion. The IRE1α activator IXA4 was administered to enhance IRE1α-XBP1 signaling activity. Motor function and pain sensitivity were evaluated using paw withdrawal mechanical threshold (PWMT), paw withdrawal thermal latency (PWTL), and gait scoring. Microglial activation was evaluated by immunofluorescence staining for ionized calcium-binding adapter molecule 1 (Iba1) and tumor necrosis factor-alpha (TNF-α). Neuronal apoptosis was assessed via TUNEL/NeuN double immunofluorescence, qRT-PCR, and Western blotting (WB). Key proteins in the IRE1α-XBP1 signaling were analyzed using WB. Results CSR rats exhibited spinal cord inflammation, neuronal apoptosis, and aberrant activation of the IRE1α-XBP1 pathway. Needle-knife therapy significantly mitigated spinal cord pathology. The treatment suppressed inflammatory cytokines, inhibited pro-inflammatory microglial activation, and inhibited activation of IRE1α-XBP1 signaling. Administration of IXA4 partially reversed these protective effects. Conclusion Needle-knife therapy ameliorates inflammation and neuronal apoptosis in CSR. These effects are associated with downregulation of the IRE1α-XBP1 signaling.