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

Abstract

Abstract. The present study was performed to investigate the role of p38 mitogen-activated protein kinase (MAPK) in the resorption of herniated intervertebral discs in 30 rats. In the non-contained 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 non-contained 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 factor-α, and interleukin-1β were observed to exhibit higher expression levels in the non-contained group compared with the contained and p38i groups, at weeks 1 and 4 post-surgery. The expression level of caspase-3 and the densities of apoptotic disc cells were significantly higher in the non-contained group compared with the contained and p38i groups at 4 weeks post-surgery. 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.

Inflammatory Processes Associated with Canine Intervertebral Disc Herniation

“…Importantly, activation of p38 and ERK in our canine samples may not only induce downstream expression of additional inflammatory mediators and matrix degrading enzymes and hence play an important role in disease progression [reviewed in Ref. ( 27 )], but may furthermore be a means to initiate resorption of non-contained herniated disc tissue ( 102 – 104 ).…”

Network Pharmacological Dissection of the Mechanisms of Eucommiae Cortex-Achyranthis Radix Combination for Intervertebral Disc Herniation Treatment

“…97 Mitogen activated protein kinase (MAPK) and Ras pathways are involved in the development and persistence of radicular pain and motor dysfunction by modulating the activities of pro-inflammatory, autophagic, and apoptotic cytokines and regulators, and targeting them can alleviate such pathological responses and further induce resorption of IVDs. [146][147][148][149][150][151][152] The repression of the mammalian target of rapamycin (mTOR) pathway can attenuate IDH-induced pain and radiculopathies. 153 The activity of the neurotrophin pathway is related to inflammatory IVD degeneration and its associated pain responses.…”

Characteristics and mechanisms of resorption in lumbar disc herniation

“…In the rat LDH model, our group observed that when the herniated IVD was ruptured or dissociated, the rate of apoptosis was higher than that of the unruptured and normal IVD [ 131 ]. Among the cytokines released by macrophage infiltration, some cytokines, such as Fas, IL-2, and HIF-α, have been shown to induce apoptosis of intervertebral disc nucleus pulposus cells, thereby promoting LDH reabsorption [ 132 – 134 ].…”

“…Wang et al [ 135 ] found that IL-2 induces apoptosis in NP cells and activates the p38 MAPK signaling pathway. Activated p38MAPK signaling pathway induces apoptosis in NP cells and accelerates the reabsorption of ruptured LDH [ 131 ].…”