The preventative effect of of Ro5-4864 (peripheral benzodiazepine receptor agonist) on spinal epidural fibrosis after laminectomy in a rat model.

OBJECTIVE: To investigate the histopathological effects of a peripheral benzodiazepine receptor agonist (Ro5-4864) on epidural fibrosis (EF) in an experimental study model (post-laminectomy) in rats. METHODS: A total of 32 albino Wistar rats were randomly divided into four equal groups (n = 8). In Group 1, no treatment was applied after laminectomy (control group). In Group 2, hemostasis was achieved after Laminectomy, and the surgical procedure was terminated by placing a 2-mm absorbable gelatin sponge dipped in saline into the epidural space. In Group 3, low-dose (4 mg/kg) Ro5-4864 was administered 30 minutes before the surgery. In Group 4, high-dose (8 mg/kg) Ro5-4864 was administered 30 minutes before the surgery. A histopathological examination was performed to evaluate arachnoidal invasion and EF. RESULTS: Our data revealed the EF was significantly reduced in rats treated with high-dose Ro5-4864 (Group 4) compared to the control and saline-soaked Spongostan groups (p = 0.000 and p = 0.006, respectively). There was no significant difference between the groups treated with high- and low-dose Ro5-4864. Arachnoidal invasion was not seen in any of the rats in the high-dose R05-4864 group. However, the arachnoidal invasion results did not significantly differ between the study groups (p = 0.052 = 0.05). CONCLUSIONS: Our study showed that Ro5-4864 could be effective in reducing EF in rats after.

Reducing the extent of facetectomy may decrease morbidity in failed back surgery syndrome.

BACKGROUND: Percutaneous transforaminal endoscopic discectomy (PTED) is widely used for the treatment of lumbar disc herniation. Facetectomy in PTED is necessary for accessing the intraspinal region and for decompressing the exiting nerve roots in patients who suffer from hypertrophy of the facet joints. However, this may increase morbidity in failed back surgery syndrome (FBSS) and has not been clearly elucidated. METHODS: A three-dimensional lumbosacral model was reconstructed and validated. And corresponding models after PTED with one-quarter and one-half excisions of the superior articular process were reconstructed. The maximum shear stress on the annulus in L5, von Mises stress of the facet cartilage, maximum principle capsular strain and deformation of the lumbosacral model were calculated using finite element methods. RESULTS: Calculated results show no significant differences in the complete model and the model with one-quarter excision of the superior articular process, but all biomechanical indexes have been deteriorated under most of the loading conditions tested in the model with one-half excision of the superior articular process. CONCLUSIONS: Less facetectomy is better because it may reduce the risk of biomechanical deterioration and consequently, that of FBSS.

Failed back surgery syndrome: a new strategy by the epidural injection of MESNA.

PURPOSE: Evaluate the efficacy and safety of MESNA (sodium 2-mercaptoethanesulfonate) injection into the epidural space in the FBSS. METHODS: We designed a prospective phase II longitudinal study. Six consecutive patients were enrolled. Patients underwent one peridural injection per week for 3 weeks. NRS and ODI were investigated before and 48 h after injections, and at 1 week, 1 month and 2 months after the last procedures. Opioids intake is investigated before procedures and 1 week, 1 month and 3 months after the last procedures. Lumbosacral MRI is performed before the first procedure, at the end and 3 months after the last procedures. RESULTS: From baseline, at 3 months, NRS in standing, sitting and lying position improved, respectively, of 34.29, 30.56 and 26.47%; ODI improved of 20.3%; the average decrease in morphine intake was 20.54%. No difference in MR images was found. Conclusions Our preliminary results suggest that MESNA might be an efficacy alternative to common practice.

Efficacy of topical cross-linked hyaluronic acid hydrogel in preventing post laminectomy/laminotomy fibrosis in a rat model.

Post-laminectomy/laminotomy epidural fibrosis (EF) has been implicated as an important cause of failed back syndrome (FBS). The various clinical approaches used to control EF yield mixed outcomes. Cross-linked hyaluronic acid hydrogel (cHA) was synthesized to increase mechanical stability and residence time. We evaluated the therapeutic attenuation of proliferative EF in laminectomy/laminotomy groups treated and not treated with cHA. A bilateral T11-L1 total laminectomy or unilateral T12 laminotomy was done on four groups (n = 10 each) of Sprague-Dawley rats and then histologically examined 2 months post-surgery: (I) laminectomy group treated with and (II) not treated with cHA, (III) laminotomy group treated with and (IV) not treated with cHA. The grade of EF, the diameters within the spinal canal, dura mater thickness, and the area of the epidural space, subarachnoid space, and conus medullaris space were assessed. The cHA-treated subgroups (I, III) had a significantly lower grade of EF, thinner dura mater, and larger epidural and subarachnoid spaces than did the control subgroups (II, IV) (p < 0.05). The cHA formed a solid interpositional membrane barrier that prevented invasive fibrosis, and also helped reduce pathological changes to the adjacent structures. In conclusion, topically applied cHA is effective for reducing EF.

Mitomycin C induces fibroblasts apoptosis and reduces epidural fibrosis by regulating miR-200b and its targeting of RhoE.

Mitomycin C (MMC) is known to reduce epidural fibrosis, but the underlying mechanisms have not yet been elucidated. Aberrant miR-200b expressions have been reported in multiple types of fibrotic tissues from many diseases. The aim of this study was to clarify the mechanism by which MMC induces fibroblasts apoptosis and reduces epidural fibrosis. The expression of miR-200b in human fibroblasts was determined after MMC treatment, and the targeted association between miR-200b and RhoE was determined using the luciferase activity assay. The effects of MMC and miR-200b on human fibroblasts apoptosis were evaluated using flow cytometry and western blot analysis. The effects of MMC and miR-200b on epidural fibrosis were evaluated using the Rydell classification, hydroxyproline content, apoptotic cell count and histological analysis. The study revealed that MMC could significantly downregulate miR-200b expression and induce human fibroblasts apoptosis. The direct downregulation of miR-200b could induce human fibroblasts apoptosis. Furthermore, we identified the binding sequence for miR-200b within the 3' untranslated region of RhoE. RhoE was confirmed to be a direct target of miR-200b, and RhoE itself acted as a promoter of fibroblasts apoptosis. The inhibition of miR-200b increased fibroblasts apoptosis and reduced epidural fibrosis in rats, which was in accordance with the effect of MMC. This study suggests that MMC induces fibroblasts apoptosis and reduces epidural fibrosis by regulating miR-200b expression and its targeting of RhoE.

Alpha-lipoic acid inhibits peridural fibrosis following laminectomy through the inactivation of TGF-ß1, PDGF, PAI-1 and IL-6 expressions.

AIM: The objective of this study was to investigate the antifibrotic effect of parenteral administration of alpha-lipoic acid (ALA), which has been reported to reduce fibrosis in the liver, oral mucosa, and peritoneum, in laminectomized rabbits as a potential candidate for the prevention of peridural fibrosis. MATERIAL AND METHODS: Twelve adult New Zealand white male rabbits were divided into control (n=6) and ALA treatment groups (n=6). Laminectomy of the lumbar spine was performed in all animals, and ALA was administered intramuscularly in six rabbits composing the treatment group. Total RNA obtained from the paraffin-embedded tissues was analyzed for transforming growth factor-ß1 (TGF-ß1), plateletderived growth factor (PDGF), plasminogen activator inhibitor-1 (PAI-1) and interleukin-6 (IL-6). RESULTS: mRNA investigations showed that TGF-ß1, PDGF, PAI-1 and IL-6 gene expressions, which constitute strong evidence for the development of fibrosis, were significantly lower in the treatment group compared with the results obtained from the control group. According to the histological peridural grading, the ALA-treated group showed significantly less peridural fibrosis than the control group. CONCLUSION: Intramuscular administration of ALA is a promising treatment for the prevention of peridural fibrosis in the postoperative period.

Immunomodulatory effectiveness of licofelone in preventing epidural fibrosis in post-laminectomy rat.

OBJECTIVE: The object of this study was to investigate the effects of licofelone on the prevention of epidural fibrosis (EF) formation in post-laminectomy rat models. METHODS: A controlled double-blinded study was conducted in sixty, healthy adult Wistar rats that underwent laminectomy at the L1-L2 vertebrae levels. All the rats were divided randomly into three groups according to the treatment (via oral gavage): (1) licofelone treatment group; (2) vehicle treatment group; (3) sham group (laminectomy without treatment). All rats were euthanized humanely 4 weeks postoperatively. The macroscopic assessment of EF, hydroxyproline content in epidural scar tissue, histological analysis, and the mRNA measurements of interleukin-6 (IL-6) and transforming growth factor-ß1 were performed. RESULTS: The Rydell score, hydroxyproline content, epidural scar density, and inflammatory factors expressions all suggested better results in licofelone group than the other two groups. CONCLUSION: The application of licofelone could reduce hydroxyproline deposits, inflammatory factors expressions and prevent epidural adhesions in post-laminectomy rats.

[Jiawei shentong zhuyu decoction prevented the occurrence of failed back surgery syndrome and its effect on serum TNF-alpha a clinical study].

OBJECTIVE: To explore the clinical roles of Jiawei Shentong Zhuyu Decoction (JSZD) in preventing the occurrence of failed back surgery syndrome (FBSS), and to observe its effect on serum tumor necrosis factor-alpha (TNF-alpha). METHODS: Totally 100 patients prepared for surgical operation due to lumbar intervertebral disc herniation were randomly assigned to the treatment group and the control group according to random number table, 50 cases in each group. Patients in the treatment group additionally took JSZD, one dose per day, taken in two portions, once in the morning and once in the evening. Those in the control group took Celecoxib Capsule (200 mg each time, once per day) and Mecobalamin Tablet (0.5 mg each time, 3 times per day). They only took Mecobalamin Tablet from the 11th day. All patients were treated for 30 days. Japanese Orthopaedic Association (JOA) score was performed before treatment, at week 1, after treatment, at 6 months of followed-ups, and at 12 months of followed-ups. And the levels of TNF-alpha in the peripheral blood were observed before treatment and at one month after treatment. RESULTS: Totally 93 patients completed the followed-up study. The JOA scores were improved after treatment, at 6 and 12 months of followed-ups (P < 0.05, P < 0.01). The JOA score at 6 months of followed-ups was superior in the treatment group to that of the control group (P < 0.05). Five patients (accounting for 10.6%) suffered from FBSS in the treatment group, while 9 (accounting for 19.6%) suffered from FBSS in the control group. The treatment group was superior to the control group (P < 0.05). The TNFalpha level was improved after treatment in the two groups. Of them, the improvement of TNF-alpha in the treatment group was better than that of the control group (P < 0.05). CONCLUSION: The application of JSZD was effective for preventing the occurrence of FBSS, and improved the serum TNF-alpha level.

Prevention of peridural fibrosis using a cyclooxygenase-2 inhibitor (nonsteroidal anti-inflammatory drug) soaked in absorbable gelatin sponge: an experimental comparative animal model.

STUDY DESIGN: Experimental study. OBJECTIVE: To evaluate the efficacy and safety of peridural parecoxib-soaked absorbable gelatin sponge, and cellulose membrane on peridural fibrosis prevention in an animal model. SUMMARY OF BACKGROUND DATA: Postoperative peridural fibrosis is one of the causes of failed back surgery syndrome. Nonsteroidal anti-inflammatory drugs inhibit the inflammatory response, while an absorbable gelatin sponge or cellulose membrane interposes between the dura and the paraspinal muscle to staunch the surgical bleeding. These mechanisms may prevent peridural fibrosis. METHODS: Forty L5-L6 laminectomized adult Sprague-Dawley rats were randomly allocated into 4 groups. The high parecoxib group received 6 mg of parecoxib soaked into an absorbable gelatin sponge placed over the dura. The low parecoxib group was given 2 mg of parecoxib soaked into an absorbable gelatin sponge. The dura in the cellulose group was covered with a cellulose membrane, while the control group received normal saline drip before surgical wound closure. All rats were killed at 6 weeks for histopathological assessment. The fibroblast density, inflammatory cell density, fibrous adherence, and adverse events were quantified. The obtained results were analyzed statistically. RESULTS: The respective mean fibroblast density in the high parecoxib, low parecoxib, cellulose, and control groups was 217.77 ± 51.76, 317.51 ± 126.92, 321.80 ± 90.94, and 328.48 ± 73.41 cells/mm², while the respective mean inflammatory cell density was 539.65 ± 236.52, 910.17 ± 242.59, 1011.84 ± 239.30, and 1261.78 ± 319.68 cells/mm². The mean fibroblast and inflammatory cell densities of the high parecoxib group were significantly lower than the control. The high parecoxib group also showed statistically less fibrous adherence than low parecoxib, cellulose, and control groups. CONCLUSION: The high-dose parecoxib-soaked absorbable gelatin sponge can prevent peridural fibrosis without complications. The low-dose parecoxib and cellulose membrane provided no significant benefit vis-à-vis prevention of peridural fibrosis, as adduced from the lack of any statistically significant difference between the test and control rats.

Alpha-lipoic acid reduces peridural fibrosis after laminectomy of lumbar vertebrae in rabbits.

BACKGROUND: Peridural fibrosis is an inevitable healing process causing failed back surgery syndrome after lumbar spinal operations. In this study, alpha-lipoic acid (ALA), reported to reduce fibrosis in liver, oral mucosa, and peritoneum, investigated as a potential candidate for prevention of peridural fibrosis. METHOD: Twelve adult New Zealand white male rabbits were divided into control (n = 5) and ALA groups (n = 7). Laminectomy of lumbar spine was performed and ALA was applied on the exposed dura mater topically in ALA group. RESULTS: According to histological peridural grading, the ALA group (median grade 1) showed significantly less peridural fibrosis than the control group (median grade 3, p = 0.005). CONCLUSIONS: ALA is a promising substance in the prevention of peridural fibrosis, especially in early preoperative and postoperative period.

Predictors of surgical, general and follow-up complications in lumbar spinal stenosis relative to patient age as emerged from the Spine Tango Registry.

INTRODUCTION: Published opinions regarding the outcomes and complications in older patients have a broad spectrum and there is a disagreement whether surgery in older patients entails a higher risk. Therefore this study examines the risk of surgery for lumbar spinal stenosis relative to age in the pooled data set of the Spine Tango registry. MATERIALS AND METHODS: Between May 2005 and February 2010 the database query resulted in 1,764 patients. The patients were subdivided into three socio-economically relevant age groups: <65 years, 65-74 years, ≥75 years. Frequencies for occurred surgical, general and follow-up complications were assessed. Multivariate and univariate logistic regressions were performed to reveal predictors for respective complication types. RESULTS AND DISCUSSION: Our study found that age, ASA status and blood loss were significant co-varieties for the occurrence of general complications. The risk of general complications is increased in older versus younger patients. Fusion or rigid stabilization does not lead to more complications. Surgical complications as well as complication rates at follow-up showed no significant age-related variation. Physician-based outcome was good or excellent in over 80% of patients in all age groups.

Prevention of scar tissue formation in spinal surgery: state of the art and review of the literature.

Recurrent radicular pain after lumbar micro-discectomy may lead to reduced quality of life of the patient. Lumbar epidural fibrosis is believed to be one of the mechanisms involved in the genesis of the pain. The use of absorbable gel temporarily separating disc remnants, muscle or bone structures from the nerve roots could reduce the amount of scar tissue surrounding the nerve, reduce tethering and therefore pain, improve outcomes and facilitate revision surgery. The author reviews the literature on prevention techniques for lumbar epidural fibrosis. The most recent studies on new compounds are encouraging in terms of safety and clinical efficacy.

Mindfulness-based stress reduction for failed back surgery syndrome: a randomized controlled trial.

CONTEXT: Previous studies on the effect of mindfulness-based stress reduction (MBSR) therapy on chronic pain syndromes have been hampered by study design. OBJECTIVE: To evaluate short-term efficacy of MBSR therapy for improving quality of life in adults with failed back surgery syndrome (FBSS). DESIGN: A single-center, prospective, randomized, single-blind, parallel-group clinical trial. PATIENTS AND SETTING: Participants were recruited from a multidisciplinary spine and rehabilitation center in the greater Portland, Maine, area. INTERVENTIONS AND MAIN OUTCOME MEASURES: Patients were randomly assigned at baseline to receive either MBSR therapy plus traditional therapy or traditional therapy alone for an 8-week period. Those receiving MBSR therapy completed weekly group sessions, and the control group continued with their traditional care as prescribed by their medical care providers. At study enrollment and at 12-week follow-up, all participants completed questionnaires on pain, quality of life, functionality, analgesic use, and sleep quality. Patients in the intervention group also completed questionnaires at 40-week follow-up. RESULTS: The final analysis included 25 patients with FBSS; 15 patients were in the MBSR intervention arm, and 10 in the control group. At 12-week follow-up, patients in the intervention arm had a mean 7.0-point increase (on an 108-point [corrected] scale) in pain acceptance and quality of life on the Chronic Pain Assessment Questionnaire, a mean 3.6-point [corrected] decrease (on a 24-point scale) in functional limitation on the Roland-Morris Disability Questionnaire, a mean 6.9-point [corrected] reduction (on a 30-point scale) in pain level on the Summary Visual Analog Scale for Pain, a mean 1.5-point [corrected] reduction (on a 4-point scale) in frequency of use and potency of analgesics used for pain and recorded on logs, and a mean 2.0-point [corrected] increase (on a 5-point scale) in sleep quality on the abridged Pittsburgh Sleep Quality Inventory. These results were statistically and clinically significant compared to outcomes for the control group. CONCLUSION: The results suggest that MBSR can be a useful clinical intervention for patients with FBSS.

[Failed back surgery syndrome].

The most confusing point in management of the patients with failed back surgery syndrome (FBSS) is that the presence of FBSS is judged not by the objective symptom such as neurological deficit evaluated by medical staff but by the subjective symptom including feeling of pain, disability and satisfaction on medical treatment. In this paper, diagnosis, cause and prevention of FBSS are summarized.

Effect of cepea extract-heparin and allantoin mixture on epidural fibrosis in a rat hemilaminectomy model.

AIM: Epidural fibrosis following a laminectomy procedure is a serious problem that results in failed back surgery syndrome. Aserious number of manuscripts have explained its possible mechanism and results but no effective preventive surgical technique or treatment is currently present. MATERIAL AND METHODS: We used a rat hemilaminectomy model at lumbar fourth level. In the treatment group (n:10), the hemilaminectomy sites were filled with cepea extract-allantoin and heparin mixture as sterile cream form. In the second group, the same surgical procedure was performed and the site was filled with physiological saline. All animals were terminated after 6 weeks and laminectomy sites removed en-bloc. Epidural fibrosis was evaluated and compared using semi-quantitative histopathological scoring scales. RESULTS: In the physiological saline group, the fibrosis score was 10.3 points and 90% of the subjects had acute inflammatory reaction, 80% chronic inflammatory reaction and 100% showed bone destruction and reparation process. In the cepea extract group, these values were fibrosis score 4.2 points, 0% acute inflammatory reaction, 33.3% chronic inflammatory reaction and 10% bone destruction and reparation process, respectively. CONCLUSION: This study showed that aloe cepea extract-allantoin and heparin mixture diminished epidural scarring formation effectively with decreased scores of acute and chronic inflammation, compared to the physiological saline solution group.

Comparison of Oxiplex and Gore-Tex effectivity in an experimental peridural fibrosis model.

OBJECTIVE: The authors conducted a study to compare the effectiveness of Oxiplex and Gore-tex in preventing postlaminectomy peridural fibrosis in rats. Peridural fibrosis is a common cause of pain in patients undergoing spinal surgery. To prevent scar formation numerous materials and methods have been employed such as non steroidal anti-inflammatory drugs (NSAIDs), Gelfoam, Oxiplex, Gore-tex, carboxymethil cellulose, Adcon-L, autogenous adipose grefting, mitomisin, and radiotherapy have been investigating for a long time, but only moderate success has been obtained. METHODS: Laminectomies were performed at the fourth lumbar vertebra (L-4) in 30 rats. Oxiplex or Gore-Tex was applied over the dura mater with the aim to perform a blinded evaluation of their effects. In the control group, only a L-4 laminectomy was performed. Animals were sacrificed 28 days after the surgical procedure. The extent of peridural fibrosis was evaluated on spine specimens by histological analysis. RESULTS: Both groups of animals treated with either Oxiplex or Gore-Tex showed a significant reduction in the degree of peridural fibrosis as compared to the control group. However no significant difference in the prevention of peridural fibrosis was observed between the Oxiplex and Gore-Tex groups. CONCLUSIONS: This experimental model has shown that Oxiplex and Gore-Tex are effective methods to prevent peridural fibrosis and dural adhesions at the postlaminectomy areas.

[Can failed back surgery be prevented? Psychological risk factors for postoperative pain after back surgery]. / Lässt sich eine "failed back surgery" verhindern? Psychologische Risikofaktoren für postoperative Schmerzen nach Wirbelsäulenoperationen.

Aside from the surgical technique used, the development of peri- and postoperative pain and impairments in patients following intervertebral disk surgery is also determined to a crucial extent by psychological factors. Based on a systematic literature review, we checked whether evidence-based recommendations could be deduced on how to take into account psychological risk factors in back surgery in order to avoid postoperative complications, such as failed back surgery syndrome. The current state of research suggests three groups of risk factors: (1) negative psychological factors, (2) preexisting pain chronification, and (3) psychological disorders. In the case of elective intervertebral disk surgery, these factors should therefore be determined and identified preoperatively and taken into account in the indication for surgery. Multimodal treatments could conceivably prove to be more effective, or else psychological pain management therapy might be considered prior to surgery so as to avoid postoperative complications. If surgery is medically unavoidable despite existing risk factors, postoperative treatment should incorporate psychological pain management therapy at an early stage in the context of a multidisciplinary approach.