The Effect of Medial Branch Block on Postoperative Residual Pain Relieve After Percutaneous Kyphoplasty: A Randomized Controlled Trial With 12-Month Follow-up.

BACKGROUND: Percutaneous kyphoplasty (PKP) is a minimally invasive technique, and effective treatment, for an osteoporotic vertebral compression fracture (OVCF). Residual back pain is the most common complication of PKP. Medial branch block (MBB) is a treatment option for painful OVCF, it can break the vicious cycle to release short- or long-term pain. OBJECTIVES: We aimed to determine the effects of MBB on postoperative residual back pain in OVCF patients after PKP surgery. STUDY DESIGN: A randomized, controlled, single-center trial. SETTING: Medical university center and local hospitals. METHODS: A total of 198 patients were recruited and randomly assigned to either the MBB or Non-MBB group. In the MBB group, patients received MBB during PKP surgery, the injection contained a mixture of lidocaine and budesonide. The Non-MBB group was injected with normal saline in the target nerve area during PKP surgery. The primary outcome was back pain assessed by the Visual Analog Scale (VAS), and residual back pain was defined as a VAS score greater than or equal to 4. The secondary outcomes included physical function assessed by Patient-Reported Outcome Measurement Information System Physical Function (PROMIS PF) and satisfaction with surgery was assessed using the S6 satisfaction scale. All parameters were measured at baseline, 1 day, 1 week, 1 month, 3, 6, and 12 months after the intervention. RESULTS: A total of 179 patients, including 91 patients in the MBB group and 88 patients in the Non-MBB group, were included for a comprehensive assessment. The VAS score in the MBB group was significantly lower than in the Non-MBB group within a one-month follow-up. PROMIS PF score in the MBB group was significantly higher than in the Non-MBB group within a one-month follow-up. The incidence of residual back pain in the MBB group was lower than the Non-MBB group within a one-month follow-up. The MBB group had a significantly higher satisfaction rate compared with the Non-MBB group at final follow-up. LIMITATIONS: Firstly, patients are from a single institution and the sample size is small. Secondly, some of the potential factors which may lead to back pain, such as infection, new symptomatic compression fracture, and serious cement leakage, did not occur. Thirdly, the conservative treatment group is not included. Finally, we were unable to determine individual differences in pain tolerance. CONCLUSIONS: MBB can effectively relieve back pain and reduce the incidence of residual back pain in OVCF patients after PKP surgery. Besides, it can also significantly improve postoperative physical function and patients' satisfaction with treatment.

An assessment of morphological and pathological changes in paravertebral muscle degeneration using imaging and histological analysis: a cross-sectional study.

BACKGROUND: The high signal of paravertebral muscle (PVM) on T2-weighted image (T2WI) is usually considered to be fatty degeneration. However, it is difficult to distinguish inflammatory edema from fatty degeneration on T2WI. The purpose of this study was to identify different types of PVM high signal in patients with low back pain (LBP) through magnetic resonance imaging (MRI) and histology. METHODS: Seventy patients with LBP underwent MRI. The signal change of multifidus both on T2WI and fat suppression image (FSI) was quantified by Image J. Furthermore, 25 of the 70 patients underwent surgery for degenerative lumbar disease and their multifidus were obtained during the operation. Histological analysis of the samples was performed by HE staining. RESULT: Three types of PVM signal changes were identified from the MRI. Type 1 (n = 36) indicated fatty degeneration characterized by a high signal on T2WI and low signal on FSI. High signal on both T2WI and FSI, signifying type 2 meant inflammatory edema (n = 9). Type 3 (n = 25) showed high signal on T2WI and partial signal suppression on FSI, which meant a combination of fatty degeneration and inflammatory edema. Histological results were consistent with MRI. Among the 25 patients who underwent surgery, type 1 (n = 14) showed adipocytes infiltration, type 2 (n = 3) showed inflammatory cells infiltration and type 3 (n = 8) showed adipocytes and inflammatory cells infiltration. CONCLUSION: From our results, there are three types of pathological changes in patients with PVM degeneration, which may help to decide on targeted treatments for LBP.

Maltol inhibits the progression of osteoarthritis via the nuclear factor-erythroid 2-related factor-2/heme oxygenase-1 signal pathway in vitro and in vivo.

Osteoarthritis (OA) is a common degenerative joint disease characterized by articular cartilage degeneration and inflammation. Currently, there is hardly any effective treatment for OA due to its complicated pathology and the severe side effects of the treatment drugs used. It has been reported that maltol, a Maillard reaction product derived from ginseng, inhibits inflammation and oxidative stress in several animal models. However, the potential anti-inflammatory effects of maltol in OA treatment are unknown. This study aimed to evaluate the anti-inflammatory effects of maltol on interleukin (IL)-1ß-induced mouse chondrocytes and protective effects of maltol on these chondrocytes in medial meniscus destabilization (DMM) OA mouse models. Mice, randomly divided into maltol (n = 15), vehicle (n = 15) and control (n = 15) groups were treated with the same dose of maltol or saline, respectively. The cartilage tissues were extracted for histological analysis 8 weeks postoperative. For the in vitro studies, chondrocytes were treated with 10 ng mL-1 IL-1ß combined with maltol at different concentrations. In vitro assays showed that the maltol pre-treatment significantly inhibited the expressions of multiple inflammatory factors induced by IL-1ß, such as inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), prostaglandin E2 (PGE2), nitric oxide (NO), interleukin-6 (IL-6) and tumor necrosis factor (TNF-α). In addition, maltol alleviated the degradation of the extracellular matrix (ECM) by inhibiting the expressions of matrix metalloproteinase-13 (MMP13) and thrombospondin motif 5 (ADAMTS5), as well as reversing the degradation of aggrecan and collagen II. Moreover, maltol suppressed nuclear factor kappa B (NF-κB) signaling by activating the nuclear factor-erythroid 2-related factor-2 (Nrf2) in in vitro and in vivo studies. These findings indicate that maltol reduces the inflammation induced by IL-1ß in chondrocytes. Therefore, the results of this study indicated that maltol may be a potential drug for the effective treatment of OA.

Inhibition of Rac1 activity by NSC23766 prevents cartilage endplate degeneration via Wnt/ß-catenin pathway.

Cartilage endplate (CEP) degeneration has been considered as one of important factors related to intervertebral disc degeneration (IVDD). Previous researches have showed that Rac1 played a pivotal role in chondrocyte differentiation. However, the effect of Rac1 during the process of CEP degeneration remains unclear. Herein, we explored the effect of Rac1 on CEP degeneration and elucidated the underlying molecular mechanism. We found expression of Rac1-GTP increased in human-degenerated CEP tissue and IL-1ß-stimulated rat endplate chondrocytes (EPCs). Our study revealed that Rac1 inhibitor NSC23766 treatment promoted the expression of collagen II, aggrecan and Sox-9, and decreased the expression of ADTAMTS5 and MMP13 in IL-1ß-stimulated rat EPCs. Moreover, we also found that NSC23766 could suppress the activation of Wnt/ß-catenin pathway, suggesting that the beneficial effects of Rac1 inhibition in EPCs are mediated through the Wnt/ß-catenin signalling. Besides, puncture-induced rats models showed that NSC23766 played a protective role on CEP and disc degeneration. Collectively, these findings demonstrated that Rac1 inhibition delayed the EPCs degeneration and its potential mechanism may be associated with Wnt/ß-catenin pathway regulation, which may help us better understand the association between Rac1 and CEP degeneration and provide a promising strategy for delaying the progression of IVDD.

Glycyrrhizin inhibits osteoarthritis development through suppressing the PI3K/AKT/NF-κB signaling pathway in vivo and in vitro.

Osteoarthritis (OA) is a serious and frequently occurring disease in the elderly, characterized by cartilage degeneration and proliferation of bone structure. Glycyrrhizin, a compound extracted from licorice, has been reported to have various important biological activities, such as antioxidant properties and anti-inflammatory action. However, it has not been reported whether glycyrrhizin has a positive effect on OA development. Our study aimed to evaluate the effects of glycyrrhizin on human OA chondrocytes. In the present study, we discovered that glycyrrhizin remarkably suppressed the interleukin (IL)-1ß-induced level of nitric oxide (NO), prostaglandin E2 (PGE2), tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6) and the production of cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOs), metalloproteinase3 (MMP3), metalloproteinase13 (MMP13) and a disintegrin and metalloproteinase with thrombospondin motifs5 (ADAMTS5). In addition, glycyrrhizin inverted the degradation of aggrecan and collagen II. Moreover, it significantly inhibited IL-1ß-stimulated PI3K/AKT phosphorylation and NF-κB mobilization in human OA chondrocytes. In vivo, glycyrrhizin treatment prevented the destruction of cartilage in mice OA models. In summary, all the results demonstrate that glycyrrhizin may be a potential therapeutic approach for OA.

Inhibition of EZH2 ameliorates cartilage endplate degeneration and attenuates the progression of intervertebral disc degeneration via demethylation of Sox-9.

BACKGROUND: Cartilaginous endplate (CEP) degeneration is considered as one of the major causes of intervertebral disc degeneration (IVDD) which causes low back pain. Recent studies have proved that epigenetic alteration is involved in a variety of diseases. This work explored the role of histone methyltransferase enhancer of zeste homologue 2 (EZH2) in CEP degeneration, as well as its underlying epigenetic mechanisms, and confirmed the effect of EZH2 knockdown on delaying IVDD development. METHODS: Western blotting, immunofluorescence staining, and ChIP assay were applied to demonstrate the molecular mechanism of EZH2 in CEP tissue. The therapeutic potential of EZH2 was investigated using puncture-induced rat models. FINDINGS: The EZH2 expression was upregulated in human and rat CEP tissue. It was also found that the overexpression of EZH2 suppressed the expression of Collagen II, aggrecan and Sox-9, and promoted the expression of ADTAMTS5 and MMP13 in rat endplate chondrocytes (EPCs), which could be reversed by EZH2 silencing. The correlation between EZH2 and Sox-9 was further explored, while overexpression of Sox-9 could reverse the effect of EZH2 in rat EPCs. Moreover, inhibition of EZH2 upregulated the level of Sox-9 by demethylating H3K27me3 at Sox-9 promoter sites, revealing the regulatory mechanism of EZH2 on Sox-9. Meanwhile, puncture-induced rat models showed that EZH2 knockdown exerted a protective effect on CEP and disc degeneration. INTERPRETATION: This study reveals that EZH2 inhibition is a promising strategy for mitigating the symptoms and progression of IVDD. FUNDING: This study was funded by the Natural Science Foundation of Zhejiang Province (Y16H060034). Authors declare that the funders had no involvement in the study design, data analysis and interpretation of the results.