The effect of resolvin D2 on radicular pain caused by lumbar disc herniation

Abstract

Objective To explore the effect of resolvin D2 (RvD2) on radicular pain induced by intervertebral disc herniation. Methods Thirty-six male Sprague-Dawley rats were randomly divided into a sham operation group, a model group and an RvD2 group, each of 12. Non-compressive lumbar disc herniation was induced in the rats in the model and RvD2 groups using the autologous nucleus pulposus filling method. Those in the sham group had the surgical site exposed without any other treatment. After the modeling, 10 μl of phosphate-buffered saline solution was administered intrathecally to the rats in the sham and model groups for 3 days, while the rats in the RvD2 group received 10 ng/10 μl of RvD2 intrathecally as well. Paw withdrawal thresholds (50%PWT) were observed 1 day before modeling and 7 days afterward for the rats of all three groups. On the 7th day after modeling, the L4 to L6 spinal dorsal horns on the surgery side were resected to detect the protein expression of phosphorylated protein kinase B (p-AKT), protein kinase B (t-AKT), phosphorylated glycogen synthase kinase 3β (p-GSK-3β) and glycogen synthase kinase 3β (GSK-3β) using western blotting. The protein levels of tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6), transforming growth factor-β1 (TGF-β1) and interleukin-10 (IL-10) were determined using enzyme-linked immunosorbent assays. Results On the 1st and 7th day after modeling, significant differences were observed between the model and sham groups in terms of the 50%PWT. From the 3rd day the average 50%PWT in the RvD2 group was significantly higher than that of the model group at the same time points. On the 7th day after the modeling the average p-AKT and p-GSK-3β protein levels of the model and RvD2 groups were significantly different from that of the sham group, and the model group′s average was also of significantly different from that of the RvD2 group. The average protein levels of the pro-inflammatory cytokines TNF-α and IL-6, as well as of the anti-inflammatory factors TGF-β1 and IL-10 in the dorsal horns of the model group and the RvD2 group were also significantly different on the 7th day, and both were significantly different from the sham group′s average. Conclusion RvD2 can alleviate radicular pain in rats with non-compressive disc herniation. The mechanisms might involve inhibition of GSK-3β activity, down-regulation of pro-inflammatory factors and up-regulation of anti-inflammatory factors. Key words: Resolvin D2; Lumbar disc herniation; Radicular pain; Inflammation; Mediators