Temperature-sensitive hydrogel loaded with DNase I alleviates epidural fibrosis in a mouse model of laminectomy

Excessive epidural fibrosis attached to the dura mater is the major cause of recurrent failed back surgery syndrome after spine surgery. Neutrophil extracellular traps (NETs) promote epidural fibrosis, raising the possibility that the DNA backbone of NETs may be a potential target in the therapy of epidural fibrosis. Human body temperature-sensitive hydroxypropyl chitin hydrogel solutions were prepared to encapsulate DNase I, which gradually decomposed in vivo. DNase I, which was released from temperature-sensitive hydrogels, destroyed the DNA backbone of NETs and dispersed the clustering of myeloperoxidase (MPO) in NETs. Evidence from MRI, H&E and Masson staining supported that hydroxypropyl chitin hydrogels loaded with DNase I were nontoxic and reduced epidural fibrosis. As expected, fibronectin in the wound was significantly abridged in the mice treated with hydrogels loaded with DNase I. Compared with the gelatin sponge absorbing DNase I, temperature-sensitive hydroxypropyl chitin hydrogels loaded with DNase I were more powerful in the therapy of epidural fibrosis. These results indicate that temperature-sensitive hydroxypropyl chitin hydrogels were effective in DNase I encapsulation and alleviation of epidural fibrosis in a mouse model of laminectomy.

The Preventive Effect of Decorin on Epidural Fibrosis and Epidural Adhesions After Laminectomy

Laminectomy is commonly performed to treat degenerative spinal diseases by reducing compression on the spinal cord and nerve roots. The postoperative epidural fibrosis and epidural adhesions may result in failed back surgery syndrome, which is characterized by the symptoms of lower back pain or leg pain. There is currently no satisfactory treatment for this complication. The pathological processes of epidural fibrosis and epidural adhesions are relevant to the proliferation of fibroblasts, transdifferentiation of fibroblasts into myofibroblasts, and the excessive deposition of extracellular matrix (ECM) protein. According to reports, transforming growth factor-β1 (TGF-β1) played a vital role in the development of fibrosis by promoting aforementioned processes. Decorin, an endogenous proteoglycan and natural inhibitor of TGF-β1, has exhibited prominent anti-fibrosis activity in various scar formation and fibrosis models of many organs. However, the preventive effect of decorin on epidural fibrosis and epidural adhesions requires further investigation. Here, we investigated the therapeutic effects and potential mechanisms of decorin on epidural fibrosis and epidural adhesions. Our results indicated that decorin could significantly suppress the TGF-β1-induced proliferation, transdifferentiation, and extracellular matrix production in primary fibroblasts. Furthermore, Smad2/3 signaling pathway had been demonstrated to be involved in the preventive effect of decorin. Moreover, administration of decorin in vivo could notably inhibit epidural fibrosis and epidural adhesions after laminectomy. To date, there is no approved therapy to target TGF-β1 for the treatment of epidural fibrosis and epidural adhesions after laminectomy. Our research proved the anti-fibrosis effect of decorin, which may provide an effective and promising treatment for epidural fibrosis and epidural adhesions.

The Influence of Missing Data on Disabilities in Patients Treated with High-Dose Spinal Cord Stimulation: A Tipping Point Sensitivity Analysis

New waveforms have changed the field of Spinal Cord Stimulation (SCS) to optimize therapy outcomes, among which is High-Dose SCS (HD-SCS). Missing observations are often encountered when conducting clinical trials in this field. In this study, different approaches with varying assumptions were constructed to evaluate how conclusions may be influenced by these assumptions. The aim is to perform a tipping point sensitivity analysis to evaluate the influence of missing data on the overall conclusion regarding the effectiveness of HD-SCS on disability. Data from the Discover study were used, in which 185 patients with Failed Back Surgery Syndrome were included. Disability was evaluated before SCS and after 1, 3 and 12 months of HD-SCS. During the second, third and fourth visit, data from 130, 114 and 90 patients were available, respectively. HD-SCS resulted in a significant decrease in disability scores based on the analysis of observed data and with multiple imputations. The tipping point sensitivity analysis revealed that the shift parameter was 17. Thus, the conclusion concerning the time effect under a “missing at random” mechanism is robust when the shift parameter for the disability score is 17. From a clinical point of view, a shift of 17 points on disability is not very plausible. Therefore we tend to consider the conclusions drawn under “missing at random” as being robust.

Efficacy of electroacupuncture in patients with failed back surgery syndrome: study protocol for a randomized controlled trial

Background Persistent pain following back surgery called failed back surgery syndrome remains a major treatment challenge. The aim of this study is to evaluate the efficacy and safety of electroacupuncture on relieving back pain in FBSS patients. Methods/design This is a randomized, single-blind, single-site, placebo-controlled trial. A total of 144 eligible FBSS patients will be randomly assigned to the electroacupuncture, manual acupuncture, or sham acupuncture group in a 1:1:1 ratio. Each group will receive 2 treatment sessions per week for 12 weeks. The primary outcome will be low back pain intensity based on the 11-point numerical rating scale (NRS). The secondary outcomes include Oswestry Disability Index (ODI) questionnaire, Beck Depression Inventory-II (BDI-II), Pittsburgh Sleep Quality Index (PSQI), and analgesic consumption. All clinical outcomes will be collected at baseline, during the treatment phase (at 8 and 12 weeks), and at the 16-, 24- and 36-week follow-ups. All data will be analyzed based on the intention-to-treat principle and adverse events will be assessed during the trial. Discussion This pilot randomized controlled trial will evaluate the efficacy of electroacupuncture for treating failed back surgery syndrome. The outcomes will determine whether electroacupuncture is efficacious in relieving low back pain as well as improving the quality of life in failed back surgery syndrome patients. Trial registration Chinese Clinical Trial Registry ChiCTR2000040144. Registered on 22 November 2020