RESUMEN
Objective To investigate the analgesic effect of Resolvin D1 (RvD1) on radicular pain induced by herniated nucleus pulposusand its underlying mechanism.Methods Fifty-six male rats were randomly divided intoa sham group,a model group,a 10 ng group anda 100 ng group,each of 14.The rat model of non-compressive lumber disc herniation was established in all except the sham group.The former two groups were then injected with 10 μl of phosphate buffer solution (PBS) while the latter 2 groups were injected with 10 μl of PBS containing 10 and 100 ng of RvD1 respectively daily for three successive days.The rats' 50％ paw withdrawal threshold (PWT) was evaluated 1 day before and on 7 successive days after surgery.On day 7 the rats' spinal cords were removed to assess the expression of tumor necrosis factor-or (TNF-α),interlukin-1β (IL-1β) and interlukin-10 (IL-10) using ELISA methods.The levels of ERK and NF-κB/p65 were measured using Western blotting.Results Theaverage 50％PWT of the model group decreased significantly from day 1 to day 7 compared with the sham group,but was significantly lower thanthe RvD1 10 ng group from day 3 to day 7.Moreover the 50％PWT in the RvD1 100 ng group increased significantlyfrom day 2 to day 7 compared with the model group (P＜0.05).The average expression of both TNF-α and IL-1β of the model group was upregulated significantly and that of IL-10 decreased significantly compared with the sham group.Compared with the model group,the expression of TNF-α and IL-1β decreased significantly (P＜0.05)and the level of IL-10 was significantlyup-regulated (P＜0.05) both in the RvD1 10 ng group and 100 ng group.Moreover,the changes were larger in the RvD1 100 ng group (P＜0.05).Compared with the sham group,the levels of p-ERK and NF-κB/p65 in the model group were significantly up-regulated (P＜0.05).Compared with the model group,intrathecal injection of RvD1 (10 ng or 100 ng) significantly decreased the expressions of p-ERK and NF-κB/p65 (P＜0.05).Moreover,the decrease wasgreater in the RvD1 100 ng group (P＜0.05).Conclusions RvD1 might alleviate the radicular inflammation and pain byregulating the balance of inflammatory mediators and activation of p-ERK and NF-κB/p65 pathways.It may offer novel therapeutic approaches for the management of lumbar disc herniation.
RESUMEN
Objective To investigate the effect of lipoxin A4 LXA4) on radicular pain caused by intervertebral disc herniation.Methods Non-compressive intervertebral disc herniation was induced into forty-eight adult male Sprague-Dawley rats,and they were divided into a sham group (sham operation + 10 μl normal saline),a control group (modeled + 10 μl normal saline),an LXA4 10 ng group (modeled + 10 ng LXA4) and an LXA4 100 ng group (modeled + 100 ng LXA4),with 12 rats in each group.The normal saline (10 μl) or LXA4 (10 μl) was administered intrathecally right after the operation and on each of the three succeeding days.General behavior was observed and the 50％ paw withdrawal threshold (50％ PWT) was measured.On postoperative day 7 all the rats were killed and the ipsilateral lumbar (L4~) segments of their spinal dorsal horns were removed for determination of the expression of p-JNK,t-JNK,p-ERK and t-ERK proteins using western blotting.TNF-α,IL-1β and TGF-β1 expression were determined using ELISA.Results There was no significant difference in the 50％PWT of the sham group before and after surgery,but the 50％ PWTs of the control group and the LXA4 10 ng group were significantly decreased after the operation compared with their values beforehand and significantly lower than the value of the sham group at all time points.Moreover,the 50％ PWT of the LXA4 10 ng group on postoperative days 3 and 5 was significantly higher than the control group;as was the value of the LXA4 100 ng group on postoperative days 2,3,4,5,6 and 7.The p-JNK and p-ERK expression in the control group,the LXA4 10 ng group and the LXA4 100 ng group were all increased significantly more than in the sham group,but their expression in the LXA4 10 ng group and LXA4 100 ng group were decreased significantly more in a dose-dependent manner compared with the control group,with the LXA4 100 ng group showing the greatest decrease.There were no significant differences in t-JNK or t-ERK expression within each group.Conclusion LXA4 can alleviate radicular pain caused by non-compressive lumbar intervertebral disc herniation.The underlying mechanism involves inhibiting the activation of the ERK and JNK pathways,reducing the expression of pro-inflammatory cytokines and increasing the expression of anti-inflammatory cytokines.