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.

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

24-month Real-World Study of Spinal Cord Stimulation in Failed Back Surgery Patients with Refractory Pain

BACKGROUND: Failed Back Surgery Syndrome (FBSS) causes disability and lowers health-related quality of life (HRQoL) for patients. Many patients become refractory to Conventional Medical Management (CMM) and Spinal Cord Stimulation (SCS) is advised. However, comparative effectiveness research of both clinical approaches still lacks further evidence. OBJECTIVES: This study describes Comparative Effectiveness Research of CMM versus SCS to provide real world evidence regarding the appropriate means for FBSS management, in terms of Patient-Reported Outcomes Measures. STUDY DESIGN: Naturalistic, pragmatic, prospective observational multicenter SEFUDOCE-study SETTING: FBSS patients attending clinical programmed visits in Pain Unit at Hospital Universitario de La Princesa and at Hospital General Universitario de Alicante (Spain). METHODS: Study evaluates the impact on pain, functional limitation, and HRQoL of CMM versus SCS in the management of FBSS. Patients completed Pain Detect Questionnaire, Oswestry Disability Index, EQ-5D-3L, Medical Outcomes Study Sleep Scale, and Hospital Anxiety and Depression Scale at baseline and at 3, 6, 12, 18 and 24 months. Longitudinal data were analysed with repeated-measures one-way analysis of variance adjusting by confounders. RESULTS: Eighty-five adults patients with FBSS receiving treatment according to current clinical practice were assessed. After 24 months, the PainDETECT Questionnnaire showed that CMM patients maintained similar scores, while SCS patients reduced their overall score (current pain: 6 CMM versus 4.21 SCS, P = 0.0091; intensity strongest pain: 7.77 CMM versus 6.07 SCS, P = 0.0103; average pain: 6.46 CMM versus 4.75 SCS, P = 0.0012). For the Oswestry Disability Index, the Medical Outcomes Study Sleep Scale, and the Hospital Anxiety and Depression Scale no significant inter-group differences were found. EQ-5D utility improved in SCS patients from baseline (baseline: 0.32 CMM versus 0.22 SCS; 24-month: 0.37 CMM versus 0.63 SCS, P = 0.026). Twenty-four month follow-up showed unlikely presence of neuropathic pain and moderate disability in SCS patients, whereas the CMM patients maintained baseline health state. LIMITATIONS: Given the nature of the intervention, conducting a blinded study was not considered practically feasible. A larger sample could also overcome having younger patients in the SCS arm. CONCLUSIONS: SCS may improve the HRQoL and functionality of FBSS patients with refractory pain in the long-term compared to CMM alone. KEY WORDS: Chronic pain management, conventional medical management, failed back surgery syndrome, observational study, spinal cord stimulation

Early Clinical Outcome of Comparative Study between Revision Operation and Radiofrequency Treatment for Management of Failed Back Surgery Syndrome

Objective: Intractable back pain and radicular pain after lumbosacral spine surgery are challenges for surgeons because the pathophysiology of failed back surgery syndrome (FBSS) remains unknown. Various medications, exercise, reoperation, spinal cord stimulation, and various interventional treatments, such as epidural injection, and radiofrequency treatment, have been suggested as treatment options. However, the clinical outcomes for each treatment are unclear. Methods: We retrospectively evaluated clinical outcomes of consecutive FBSS patients who underwent revision operation or radiofrequency treatment from 2014 to 2017, who previously showed response to nerve block. Pain was analyzed preoperatively and 1 month, 6 months, and 12 months postoperatively using a visual analogue scale (VAS). Short Form 36 (SF-36) health survey and Oswestry Disability Index (ODI) scores were assessed preoperatively and 12 months postoperatively. Results: A total of 70 patients was included in the present study (33 males, 37 females). When comparing preoperative and postoperative 12-month results, back pain VAS score decreased from 5.5 to 4.2 for revision operation and from 5.1 to 4.7 for radiofrequency treatment. Leg pain VAS score decreased from 6.5 to 4.02 for revision operation and 6.2 to 4.3 for radiofrequency treatment. ODI score decreased from 70.9 to 36.1 for revision operation and 70.2 to 36.1 for radiofrequency treatment. SF-36 score increased from 28.9 to 64.1 for revision operation and from 29.6 to 59.6 for radiofrequency treatment. Differences between treatments were not statistically significant after 12 months (p>0.05) but were at 1 month (p=0.01). Conclusion: Compared with revision operation, radiofrequency treatment is not inferior on early clinical outcome (up to 1 year following the treatment) in terms of pain relief, functional capacity, patient satisfaction, and quality of life in patients with FBSS. Radiofrequency treatment can be considered in patients who are not good candidates for surgical treatment based on imaging results or underlying diseases and who are responsive to diagnostic/therapeutic nerve blocks.