p38 mitogen-activated protein kinase inhibition modulates nucleus pulposus cell apoptosis in spontaneous resorption of herniated intervertebral discs: An experimental study in rats.

The present study was performed to investigate the role of p38 mitogen­activated protein kinase (MAPK) in the resorption of herniated intervertebral discs in 30 rats. In the non­contained and p38 MAPK inhibition (p38i) groups, two coccygeal intervertebral discs (IVDs) were removed and wounded prior to relocation into the subcutaneous space of the skin of the back. In the contained group, the cartilage endplates maintained their integrity. Furthermore, SB203580 was injected intraperitoneally into the p38i group, whereas saline was injected into the other two groups. In the non­contained group, the weight of the relocated IVDs decreased to a greater extent over time when compared with the contained and p38i groups. Phosphorylated p38, tumor necrosis factor­α, and interleukin­1ß were observed to exhibit higher expression levels in the non­contained group compared with the contained and p38i groups, at weeks 1 and 4 post­surgery. The expression level of caspase­3 and the densities of apoptotic disc cells were significantly higher in the non­contained group compared with the contained and p38i groups at 4 weeks post­surgery. In conclusion, p38 MAPK induces apoptosis in IVDs, while also accelerating the resorption of the relocated IVDs. Thus, p38 MAPK may be important in spontaneous resorption of IVDs.