Low back pain due to epidural fibrosis is a major complication after spine surgery. Macrophages infiltrate the wound area post laminectomy, but the role of macrophages in epidural fibrosis remains largely elusive. In a mouse model of laminectomy, macrophage depletion decreased epidural fibrosis. CD146, an adhesion molecule involved in cell migration, is expressed by macrophages. CD146-defective macrophages exhibited impaired migration, which was mediated by reduced expression of CCR2 and suppression of the MAPK/ERK signaling pathway. CD146-defective macrophages suppress the MAPK/ERK signaling pathway by increasing Erdr1. In vivo, CD146 deficiency decreased macrophage infiltration and reduced extracellular matrix deposition in wound tissues. Moreover, the anti-CD146 antibody AA98 suppressed macrophage infiltration and epidural fibrosis. Taken together, these findings demonstrated that CD146 deficiency alleviates epidural fibrosis by decreasing the migration of macrophages via the Erdr1/ERK/CCR2 pathway. Blocking CD146 and macrophage infiltration may help alleviate epidural fibrosis.

Postoperative epidural fibrosis (EF) is still a major limitation to the success of spine surgery. Fibrotic adhesions in the epidural space, initiated via local trauma and inflammation, can induce difficult-to-treat pain and constitute the main cause of failed back surgery syndrome, which not uncommonly requires operative revision. Manifold agents and methods have been tested for EF relief in order to mitigate this longstanding health burden and its socioeconomic consequences. Although several promising strategies could be identified, few have thus far overcome the high translational hurdle, and there has been little change in standard clinical practice. Nonetheless, notable research progress in the field has put new exciting avenues on the horizon. In this review, we outline the etiology and pathogenesis of EF, portray its clinical and surgical presentation, and critically appraise current efforts and novel approaches toward enhanced prevention and treatment.

Epidural fibrosis (EF), associated with various biological factors, is still a major troublesome clinical problem after laminectomy. In the present study, we initially demonstrate that sensory nerves can attenuate fibrogenic progression in EF animal models via the secretion of calcitonin gene-related peptide (CGRP), suggesting a new potential therapeutic target. Further studies showed that CGRP could inhibit the reprograming activation of fibroblasts through PI3K/AKT signal pathway. We subsequently identified metformin (MET), the most widely prescribed medication for obesity-associated type 2 diabetes, as a potent stimulator of sensory neurons to release more CGRP via activating CREB signal way. We copolymerized MET with innovative polycaprolactone (PCL) nanofibers to develop a metformin-grafted PCL nanoscaffold (METG-PCLN), which could ensure stable long-term drug release and serve as favorable physical barriers. In vivo results demonstrated that local implantation of METG-PCLN could penetrate into dorsal root ganglion cells (DRGs) to promote the CGRP synthesis, thus continuously inhibit the fibroblast activation and EF progress for 8 weeks after laminectomy, significantly better than conventional drug loading method. In conclusion, this study reveals the unprecedented potential of sensory neurons to counteract EF through CGRP signaling and introduces a novel strategy employing METG-PCLN to obstruct EF by fine-tuning sensory nerve-regulated fibrogenesis.

Introduction Lumbar and leg pain can be caused by many factors, including scar tissue in the epidural space. Epidural fibrosis may cause chronic radicular low back pain. Adhesions in the epidural space may occur due to surgical or non-surgical reasons. Epidural adhesiolysis, i.e., neuroplasty, eliminates the pain-causing effects of scar tissue by releasing the nerve from the scar tissue or decompressing the nerve. In light of this information, this study was conducted to evaluate the effectiveness of percutaneous epidural neuroplasty interventions performed in the algology clinic in patients with lumbar epidural fibrosis who have and have not undergone lumbar surgery. Methods The sample of this retrospective study consisted of 72 patients with chronic radicular low back pain, finding fibrosis in the epidural region on contrast-enhanced magnetic resonance imaging (MRI), filling defect after epidurogram, and caudal epidural neuroplasty. Patients\' visual analog scale (VAS) and Oswestry disability index (ODI) scores, pregabalin, duloxetine, and opioid doses were evaluated before and one month and six months after having neuroplasty. Results The VAS and ODI scores and pregabalin, duloxetine, and opioid doses decreased significantly in patients who had had caudal epidural neuroplasty at post-procedure endpoints compared to before the procedure (p<0.001). The paired temporal comparisons of the data of the patients who underwent epidural neuroplasty procedures before the procedure, one month after the procedure, and six months after the procedure revealed significant differences in the VAS and ODI scores (p<0.001). Additionally, the analysis of patients\' VAS scores revealed that the pre-procedure VAS scores decreased significantly more one month after the procedure in patients without a history of lumbar surgery than in patients with a history of lumbar surgery. Conclusions The findings of our study demonstrated that fluoroscopy-guided percutaneous epidural neuroplasty alleviated pain and improved physical functions and quality of life. In conclusion, percutaneous epidural neuroplasty is a safe and effective treatment method for patients with lumbar epidural fibrosis.

UNASSIGNED: Histopathological examination of the effects of Tisseel, Cova, Glubran and Coseal, which are used for sealing purposes in spinal surgery practice, on epidural fibrosis is aimed.
UNASSIGNED: Forty Sprague Dawley rats were randomly divided into five groups in our study as Group 1 (n=8) control group (Laminectomy); Group 2 (n=8) Cova group (Laminectomy + Cova); Group 3 (n=8) Tissel group (Laminectomy + Tisseel); Group 4 (n=8) Coseal group (Laminectomy + Coseal); and Group 5 Glubrane group (Laminectomy + Glubrane). Control group was only applied laminectomy. After laminectomy to other groups, Cova was applied to the 2nd group, Tissel to the 3rd group, Coseal to the 4th group and Glubran to the 5th group in surgical fields. After the rats were monitored in separate cages for 6 weeks after the operation, the relevant spinal level was extracted and the samples were examined histopathologically and the results were evaluated statistically.
UNASSIGNED: It was found that there was a statistically significant difference in Tisseel and Glubran groups in terms of fibrosis grading compared to the control group, and this had a positive effect on fibrosis. Compared to the control group, there was no statistically significant difference on fibrosis in Cova and Coseal groups.
UNASSIGNED: As dura adhesive agents used in spinal surgery practice did not increase spinal epidural fibrosis statistically significantly, we concluded that these products can be used safely during spinal surgery if necessary.

Laminectomy is a widely employed surgical procedure for the treatment of spinal stenosis, but it may lead to epidural fibrosis (EF) and failed back surgery syndrome. Cinnamaldehyde, a phenylpropanoid found in cinnamon, has demonstrated antioxidant and anti-inflammatory properties. In the present study, we hypothesized that topical application and systemic administration of cinnamaldehyde could be helpful in the prevention of EF in a rat laminectomy model.
The rats were randomly assigned to control, local, and systemic Tween-80 and local and systemic cinnamaldehyde experimental groups (n = 6, per group). In the control group, just laminectomy was performed. In local treatment groups, applications were done just after the laminectomy onto dura. In systemic treatment groups, intraperitoneal administrations were performed following skin suturing. The degree of epidural fibrosis was evaluated macroscopically and histopathologically 4 weeks later.
Macroscopic assessment revealed decreased EF with both topical and systemic cinnamaldehyde application, whereas microscopic examination results were not significant.
Our findings provide the first experimental evidence of cinnamaldehyde\'s potential protective effects against EF.

Epidural fibrosis after all spinal surgeries is an important surgical issue. Various biological and non-biological materials have been tried to inhibit epidural fibrosis, which is deemed to be the most important cause of pain after spinal surgery. Olive oil, nigella sativa oil and soybean oil employed in oral nutrition in clinics involving liquid fatty acids, palmatic acid, linoleic acid, stearic acid and palmitoleic acid. The effectiveness of olive oil, nigella sativa oil and soybean oil on epidural fibrosis was researched on for the first time in laminectomy model.

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Fifty adult male Wistar albino rats weighing between 300 and 400 grams were used in the research. A total of 5 groups were formed: sham (Group I) (n = 10), no application was created; Group II (n = 10) 1 cc saline; Group III (n = 10) 1 cc olive oil; Group IV (n = 10) 1 cc nigella sativa oil; Group V (n = 10); 1 cc soybean oil was applied topically to the epidural region after laminectomy. The total spine of the rats was dissected, histopathological and immuno­chemical measurements were conducted. Neuro-histopathological results were scored semi-quantitatively in terms of vascular modification, neuron degeneration, gliosis and bleeding criteria.

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The lowest level of fibrosis and connective tissue proliferation was observed in the group where nigella sativa oil was used after the operation, followed by the group treated with olive oil and lastly with the group given soybean oil.

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Nigella sativa oil and olive oil are very efficient for lowering the degree of epidural fibrosis and adhesions following laminectomy and can be employed as a simple, inexpensive and highly biocompatible material in clinical practice.

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Az epiduralis fibrosis minden gerincműtét után fontos sebészeti probléma. Különböző biológiai és nem biológiai anyagokkal próbálták gátolni az epiduralis fibrosist, amit a gerincműtétek utáni fájdalom legfontosabb okának tartanak. Az olívaolaj, a Nigella sativa (fekete kömény) olaj és a szójaolaj a klinikákon a táplálásban szájon át alkalmazott, palmatinsav-, linolsav-, sztearinsav- és palmitoleinsav-tartalmú folyékony zsírsavak. Az olívaolaj, a Nigella sativa-olaj és a szójaolaj hatékonyságát az epiduralis fibrosisra kutatócsoportunk vizsgálta először laminectomiás modellben.

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Ötven felnőtt, 300–400 gramm közötti súlyú hím Wistar albínó patkányt hasz­náltunk a kutatásban. Összesen öt cso­portot alakítottunk ki: sham (I. csoport) (n = 10), nem volt kezelve; II. csoport (n = 10) 1 koncentrált sóoldat; III. csoport (n = 10) 1 koncentrált olí­vaolaj; IV. csoport (n = 10) 1 koncentrált Ni­gella sativa-olaj; V. csoport (n = 10); 1 kon­centrált szójaolajat helyileg alkalmaztunk az epiduralis régióra a laminectomia után. A pat­kányok teljes gerincét felboncoltuk, szövettani és immunkémiai méréseket végeztünk. A neu­rohisztopatológiai eredményeket fél­kvantitatív módon pontoztuk az érrendszeri elváltozás, a neuronok degenerációja, a gliosis és a vérzési kritériumok alapján.

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A fibrosis és a kötőszöveti proliferáció legalacsonyabb szintje abban a csoportban volt megfigyelhető, ahol a műtét után Nigella sativa-olajat használtak, ezt követte az olívaolajjal kezelt csoport, végül pedig a szójaolajjal kezelt csoport.

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A Nigella sativa-olaj és az olívaolaj nagyon hatékonyan csökkenti a laminectomiát követő epiduralis fibrosist és az összenövések mértékét, és egyszerű, olcsó és nagymértékben biokompatibilis anyagként alkalmazhatók a klinikai gyakorlatban.

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OBJECTIVE: We propose a vast study to examine the effect of high-frequency bipolar coagulation used in the operating room to prevent the development of epidural fibrosis after lumbar microdiscectomy.
METHODS: A total of 1004 participants were divided into two groups: no high-frequency bipolar coagulation (NC group) and high-frequency bipolar coagulation (C group). Postoperative epidural fibrosis, infection rates, reoperation status, and dural injury complications during the operation were recorded.
RESULTS: Considering the epidural fibrosis rates of the two groups, epidural fibrosis was seen in 10.6% of the patients in the NC group. In contrast, it was seen in only 6.2% of the patients in the C group.
CONCLUSIONS: The complication of epidural fibrosis that develops after lumbar microsurgery operations both impairs patient comfort and brings with it the complications of reoperation. After performing hemostasis with bipolar, coagulating the annulus may effectively reduce epidural fibrosis and prevent reoperation.

UNASSIGNED: Epidural fibrosis is one of the problems that can be seen after spinal surgery. The aim of this study was to investigate the possible preventive role of medical ozone (O) treatment on epidural fibrosis.
UNASSIGNED: Twenty-four Sprague Dawley rats were randomly split into four groups: control (C), O, laminectomy (L), and L+O groups. Animals in the C group were sacrificed at the beginning of the experiment. The L and L+O groups had L procedure, while O treatment was supplied for the O and O+L groups. After 42 days of follow-up, for histological evaluation and biochemical measurements, the ratio of epidural fibrosis and catalase (CAT) with malondialdehyde (MDA) levels in serum, respectively, were analyzed in terms of statistical differences.
UNASSIGNED: Histologically, a distinct difference was o bserved in the epidural space after O treatment. A significant difference in epidural fibrosis areas is found to be between the O, L, and O+L groups (P < 0,0001). There was no statistically significant difference between CAT and MDA levels that were obtained by spectrophotometric analysis.
UNASSIGNED: Histological results suggest that medical O treatment after L can be used as an alternative method to prevent epidural fibrosis. Further studies with wide cohorts and interval measures are required to detail the effects of doses.

OBJECTIVE: The present study aimed to determine the topical and systemic efficacy of tranexamic acid (TXA) on epidural fibrosis in a rat laminectomy model.
METHODS: Thirty-two 12-month-old adult Sprague-Dawley rats were used in this study. Each rat underwent bilateral laminectomy at the L1 and L2 vertebral levels. Rats were divided into four groups : in group I (control group, n=8), a laminectomy was performed and saline solution was applied into the surgical space. In group II (topical group, n=8), laminectomy was performed and 30 mg/ kg TXA was applied to the surgical site before skin closure. In group III (systemic group, n=8), 30 mg/kg TXA was administered intravenously via the tail vein in the same session as the surgical procedure. In group IV (topical and systemic group, n=8), TXA was administered 30 mg/kg both topical and intravenous. The rats were sacrificed at 4 weeks postoperatively. Masson\'s trichrome and hematoxylin and eosin were used to assess acute inflammatory cells, chronic inflammatory cells, vascular proliferation, and epidural fibrosis.
RESULTS: Epidural fibrosis, acute inflammation, chronic inflammation, and sum histologic score value were significantly lower in the systemic TXA group, systemic and topical TXA groups than in the control group (p<0.05). In addion, the sum histologic score was significantly lower in the topical TXA group than in the control group (p<0.05).
CONCLUSIONS: In this study, epidural fibrosis formation was prevented more by systemic application, but the topical application was found to be effective when compared to the control group. As a result, we recommend the systemic and topical use of TXA to prevent epidural fibrosis during spinal surgery.