• Yi Zhong, Yangliang Huang, Yuming Hu, Mingxian Xu, Lirong Zhu, and Zhen Deng.
• Key Laboratory of Neuroscience, School of Basic Medical Science, Guangzhou Medical University, Guangzhou, China.
• Spine. 2019 Oct 1; 44 (19): E1112-E1121.

Study DesignA controlled, randomized, animal study.ObjectiveThe aim of this study was to investigate the role of src-family kinases/p38 pathway in a rat model of lumbar disc herniation (LDH).Summary Of Background DataLDH always generates radicular pain, and the mechanism remains unclear. We have reported that spinal src-family kinases (SFKs) may be involved in the process, but the downstream mechanism needs further investigation.MethodsLDH was induced by implantation of autologous nucleus pulposus (NP), harvest from the tail, in lumbar 4/5 spinal nerve roots of rat. Von Frey filaments and radiant heat tests were performed to determine mechanical and thermal pain threshold respectively. Basso, Beattie, and Bresnahan (BBB) scale was assessed to test the locomotor function. The protein level of p-SFKs, t-SFKs, p-p38, t-p38 in spinal cord was examined by western blotting analysis. Cellular location of p-p38 was determined by immunochemistry staining. Spinal tumor necrosis factor-alpha (TNF-α), interleukin (IL)-1β, and IL-6 levels were detected by enzyme-linked immunosorbent assay (ELISA).ResultsRats with NP implantation showed persistent ipsilateral mechanical allodynia and thermal hyperalgesia, which manifested as obvious decrease of paw withdrawal threshold (PWT) and paw withdrawal latency (PWL). BBB scale indicated the locomotor function of hindpaws in rats with NP implantation kept intact. Western blotting and immunohistochemistry staining revealed that phosphorylated SFKs (p-SFKs) and phosphorylated p38 MAPK (p-p38) were sequentially upregulated in ipsilateral spinal dorsal horn, but not in contralateral side of rats with NP. Intrathecal delivery of SFKs inhibitor reduced spinal p-p38 expression. Both SFKs and p38 inhibitors alleviated pain behaviors in a dose-responsive manner without disturbing locomotor function and reduced spinal expression of TNF-α, IL-1β, and IL-6 in rats with NP.ConclusionSpinal SFKs contribute to radicular pain by activation of p38 MAPK and increasing pro-inflammatory cytokines expression in rats with NP implantation. Targeting SFKs/p38 pathway may be helpful for alleviating radicular pain.Level Of EvidenceN/A.

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