One of the primary causes of Failed Back Syndrome is peridural fibrosis (PF),Citation2 which is characterized by overproduction of scar tissue between dura mater and surrounding tissue following laminectomy.Citation1
PF following spinal surgery, results in adhesion generation around the neural tissue, causing neural entrapment symptoms similar to those existing prior to surgery and may require additional surgery that however may lead to serious complications, and is more challenging or even dangerous.Citation3
Various biophysical barriers (such as ADCON-L, hyaluronic acid) and pharmacological agents (such as steroids, mitomycine-C, aprotinin, etc.) have been used to prevent overproduction of scar tissue, thus reducing the risk for PF, but only limited success has been achieved.
Although therapeutic activities of some have been reported; no adequate solution has been defined to reduce the PF formation, yet.
Hyaluronic acid, synthesized in the human body, can inhibit the cytokine formation and reduce the lymphocyte, macrophage, and granulocyte migration into the extracellular matrix in vitro and for these properties, it has been used in some clinics to reduce epidural fibrosis formation.Citation4,Citation5
Polyethylene glycol, which is both biocompatible and neurocompatible polymer, may not come in collision with healing process and it used to be a biological barrier in many surgical areas and as dural barrier in neurosurgery, but there is insufficient data about its effects to the formation of epidural fibrosis in literature.Citation6–7
Platelet rich plasma (PRP) has been successfully used in Orthopedics and Rheumatology and in many other fields, but its impact on the formation of the PF has not been fully identified.Citation8
Since the problem of PF following decompression remains open for investigation both in animals and human beings, in this study, the authors compared four biophysical barriers (hyaluronic acid, dural barrier, activated polyethylene glycol and polyethylene imine dural barrier and platelet rich plasma) in reducing the occurrence of PF following wide (L3 to L5) laminectomy in animal model (Wistar albino rats).Citation9
In this investigation study, 2 of 26 rats, were sacrificed by removing their total blood that was used for preparation of PRP, while the remaining 24 rats were randomly included into 4 groups (SHAM-no agent, HAS, PEG, and PRP). The way for randomization is not described by the authors. Then L3 to L5 laminectomy was performed in all 24 rats and experimental agents were administered to all rats.
The surgical technique, which the authors described, seems to be autraumatic (surgical microscope, no cauterization to the surgical side etc.) and this seems for me to reduce possible mechanical provocation and development of PF. An advantage in methods section (inclusion criteria) is the rejection of rats with surgery-related neurologic lesion to avoid misinterpretation of the obtained results.
Histopathology, which was performed post-mortem in spinal colons from all animals was correct since well established methods (Haematoyxlin-eosin staining and Massons trichrome), were used. To examine fibrosis thickness the authors accurately took five random regions of the specimens, thus increasing the reliability of the results. The grading of the fibrosis was made using the established method by Kasimcan MO et al.Citation10 Real-time PCR gene expression analysis was performed by using the gene expression Kits. The statistical methods used are the appropriate, although I cannot understand the reason of taking P-values < 0.0083 for Tukey HSD Multiple Comparisons test and the Bonferroni correction test.
However, a weak point is the lack of power analysis to determine if the number of the rats included in each group was adequately enough to test the hypothesis of this study. The latter should be taken in consideration because one rat from the SHAM group and 2 from the HAS group, were left out of study. This theoretically, decreases the number of the rats in these two groups and might furthermore decrease the value of the results derived from this study.
Another issue is the lack of any cultures for bacteria after rats' death in the retrieved specimens, however in contrary there are histopathological findings against infection.
Correctly, according to the relative literature, real time-polimerase chain reaction was used to obtain Collagen type-1 and type-3, transforming Growth Factor-1β, and Tumor Necrosis Factor-α gene expressions.
As the authors reported in the final paragraph of the Discussion there were some limitations, from which I see only the lack of advanced immunohistochemical and other advanced histopathological analysis methods (fluorescence microscopy, electron microscopy) and advanced biochemical analysis methods (westerns blood, ELISA).
Generally, the authors made a good job in this experimental study demonstrating that polyethylene glycol and polyethylene imine dural barrier and platelet rich plasma could decrease PF formation in rats.
Based on the results of this well performed investigation, I recommend further investigations in animals and humans beings.
DECLARATION OF INTEREST
The author has no conflict of interest
REFERENCES
- Skaf G, Bouclaous C, Alaraj A, Chamoun R. Clinical outcome of surgical treatment of failed back surgery syndrome. Surg Neurol. 2005;64:483e489. doi:10.1016/j.surneu.2005.04.009.
- Zhang C, Kong X, Ning G, Liang Z, Qu T, Chen F. All-trans retinoic acid prevents epidural fibrosis through NF-kB signaling pathway in post-laminectomy rats. Neuropharmacology. 2014;79:275e281. doi:10.1016/j.neuropharm.2013.11.010.
- Ronnberg K, Lind B, Zoega B, Gadeholt-Gothlin G, Halldin K, Gellerstedt M, et al. Peridural scar and its relation to clinical outcome: a randomised study on surgically treated lumbar disc herniation patients. Eur Spine J. 2008;17(12):1714–1720. doi:10.1007/s00586-008-0805-8. PMID:18946688.
- Kato T, Haro H, Komori H, Shinomiya K. Evaluation of hyaluronic acid sheet for the prevention of postlaminectomy adhesions. Spine J. 2005;5(5):479–488. doi:10.1016/j.spinee.2005.01.010. PMID:16153573.
- Leask A, Abraham DJ. TGF-beta signaling and the fibrotic response. FASEB J. 2004;18(7):816–826. doi:10.1096/fj.03-1273rev. PMID:15117886.
- Bakar B, Kose EA, Balci M, Atasoy P, Sarkarati B, Alhan A, et al. Evoluation of the neurotoxicity of the polyethylene glycol hydrogel dural sealant. Turk Neurosurg. 2013;23(1):16–24 PMID:23344862.
- Weinstein JS, Liu KC, Delashaw JB Jr, Burchiel KJ, van Loveren HR, Vale FL, et al. The safety and effectiveness of a dural sealant system for use with nonautologous duraplasty materials. J Neurosurg. 2010;112(2):28–43. doi:10.3171/2009.6.JNS081540.
- Yan L, Li X, Wang J, Sun Y, Wang D, Gu J. Immunomodulatory effectiveness of tacrolimus in preventing epidural scar adhesion after laminectomy in rat model. Eur J Pharmacol. 2013;699:194e199. doi:10.1016/j.ejphar.2012.11.037.
- Effectivity of biophysical barriers in Peridurla Fibrosis. J Invest Surg. (In press).
- Kasimcan MO, Bakar B, Aktas S, Alhan A, Yilmaz M. Effectiveness of the biophysical barriers on the peridural fibrosis of a postlaminectomy rat model: an experimental research. Injury. 2011;42(8):778–781. doi:10.1016/j.injury.2010.12.017. PMID:21392759.