ABSTRACT
Intervertebral disc degeneration (IDD) is a chronic skeletal muscle degenerative disease, which is considered the main cause of low back pain. It seriously affects the quality of life of patients and consequently brings a heavy economic burden to their families and the society. Although IDD is considered a natural process in degenerative lesions, it is mainly caused by aging, trauma, genetic susceptibility and other factors. It is closely related to changes in the tissue structure and function, including the progressive destruction of extracellular matrix, cell aging, cell death of the intervertebral disc (IVD), inflammation, and impairment of tissue biomechanical function. Currently, the treatment of IDD is aimed at alleviating symptoms rather than at targeting pathological changes in the IVD. Furthermore, the mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) signaling pathway is closely related to various pathological processes in IDD, and the activation of the MAPK/ERK pathway promotes the degradation of the IVD extracellular matrix, cell aging, apoptosis, and inflammatory responses. It also induces autophagy and oxidative stress that accelerate the IVD process. In our current review, we summarize the latest developments in the negative regulation of IDD after activation of the MAPK/ERK signaling pathway and emphasize on its influence on IDD. Targeting this pathway may become an attractive treatment strategy for IDD in the near future.
Subject(s)
Anti-Inflammatory Agents/therapeutic use , Extracellular Signal-Regulated MAP Kinases/antagonists & inhibitors , Intervertebral Disc Degeneration/drug therapy , Intervertebral Disc/drug effects , Protein Kinase Inhibitors/therapeutic use , Animals , Extracellular Matrix/drug effects , Extracellular Matrix/enzymology , Extracellular Matrix/pathology , Extracellular Signal-Regulated MAP Kinases/metabolism , Humans , Inflammation Mediators/metabolism , Intervertebral Disc/enzymology , Intervertebral Disc/pathology , Intervertebral Disc/physiopathology , Intervertebral Disc Degeneration/enzymology , Intervertebral Disc Degeneration/pathology , Intervertebral Disc Degeneration/physiopathology , Molecular Targeted Therapy , Signal TransductionABSTRACT
BACKGROUND: Lumbar fusion is considered to the gold standard for treatment of spinal degenerative diseases but results in adjacent segment degeneration and acquired spinal instability. Total disc replacement is a relatively new alternative avoiding the occurrence of the above complications. The systematic review and meta-analysis was designed to evaluate whether total disc replacement exhibited better outcomes and safety. METHODS: PubMed, Web of Science, Embase, the Cochrane Library, Chinese National Knowledge Infrastructure Database(CNKI), Wangfang database, and VIP database were searched for RCTs comparing total disc replacement with lumbar fusion. All statistical analyses were carried out using the RevMan5.3 and STATA12.0 software. RESULTS: Of 1116 citations identified by our search strategy, 14 RCTs met the inclusion criteria. Compared to lumbar fusion, total disc replacement significantly improved ODI, VAS, SF-36, patient satisfaction, overall success, reoperation rate, ODI successful, reduced operation time, shortened duration of hospitalization, decreased postsurgical complications. However, total disc replacement did not show a significant difference regarding blood loss, consumption of analgesics, neurologic success and device success with lumbar fusion. And charges were significantly lower for total disc replacement compared with lumbar fusion in the 1-level patient group, while charges were similar in the 2-level group. CONCLUSION: Total disc replacement is recommended to alleviate the pain of degenerative lumbar diseases, improve the state of lumbar function and the quality of life of patients, provide a high level of security, have better health economics benefits for 1-level patients.
Subject(s)
Intervertebral Disc Degeneration/surgery , Lumbar Vertebrae/pathology , Spinal Fusion , Total Disc Replacement , Humans , Intervertebral Disc Degeneration/diagnosis , Randomized Controlled Trials as Topic , Spinal Fusion/adverse effects , Spinal Fusion/methods , Total Disc Replacement/adverse effects , Total Disc Replacement/methods , Treatment OutcomeABSTRACT
OBJECTIVE: We aimed to perform a systematic review and meta-analysis to compare the treatment effects of unstable shoes and flat shoes on lower back pain patients. DATA SOURCES: Literature databases, including PubMed, Web of Science, and EMBASE (up to June 2019), were searched systematically. REVIEW METHODS: Two authors independently screened the retrieved records and identified the randomized controlled trials where patients with lower back pain who wore unstable shoes as intervention and wore flat shoes as a control. Relevant data were extracted for meta-analysis using Review Manager 5.3 software. The Grading of Recommendations Assessment, Development and Evaluation approach was used to assess the pooled outcome evidence levels. RESULTS: Five randomized controlled trials and 251 patients were included in the analysis. The meta-analysis results showed that there was a tendency toward a reduction in the Roland-Morris disability questionnaire score (mean difference (MD) -2.16, 95% confidence interval (CI) -4.28 to -0.03, I2 = 53%) and pain score (MD -0.84, 95% CI -1.66 to -0.02, I2 = 84%) in patients wearing unstable shoes compared to those wearing flat shoes. There was no significant difference in the life quality scores between the unstable shoe and flat shoe groups (MD -0.59, 95% CI -6.18 to 5.01, I2 = 0%). Functional disability and pain scores were determined to have very low-quality evidence, and life quality scores were determined to have low-quality evidence according to the Grading of Recommendations Assessment, Development and Evaluation analysis. CONCLUSION: Unstable shoes may be effective in treating lower back pain in the clinic, but the conclusion was limited by the current low-quality studies.
