Clinical study on the treatment of discogenic low back pain by endoscopic "isolation zone" technique through pedicle-flavum tunnel

Clinical study on the treatment of discogenic low back pain by endoscopic "isolation zone" technique through pedicle-flavum tunnel | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Clinical study on the treatment of discogenic low back pain by endoscopic "isolation zone" technique through pedicle-flavum tunnel lu wang, cai cheng, lingxia li, yuan xue This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-1761550/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Objective : To explore the surgical strategy and clinical effects of the "isolation zone" technique through pedicle-flavum tunnel for the treatment of discogenic low back pain under percutaneous spinal endoscopy. Methods : From September 2017 to September 2020, the author treated patients with intervertebral discogenic low back pain with lateral approach percutaneous spinal endoscopic surgery under local anesthesia. The working channel is inserted through the anatomical pedicle-flavum tunnel and performed neuralization and corresponding segmental nerve roots are decompressed throughout the process, forming an "isolation zone" around the nerve root without contact with the nucleus pulposus and annulus fibrosus. The visual analogue scale (Visual Analogue Scale, VAS) and Oswestry Disability Index (ODI) of low back pain and pain around the buttocks were recorded before and 1, 3, 6, and 12 months after the operation, and the modified MacNab criteria were evaluated. curative effect. A total of 45 patients completed surgery and received complete postoperative follow-up. Results : The 45 patients in this group all completed the operation successfully. There was no patient who could not tolerate the pain of local anesthesia and was forced to interrupt. The operation time was 65 to 125 minutes, with an average of 94.71±17.67 minutes. The average follow-up time for all patients was 12-18 months. , An average of 13.6±1.9months, the VAS scores for lower back pain and pain around the hips were 6.95±1.02 before surgery, 2.64±0.71 at 1 month after surgery, 1.80±0.54 at 3 months after surgery, and at 6 months after surgery 1.42±0.50, 12 months after surgery, 1.27±0.45; Oswsetry dysfunction index was 72.84±5.95 before surgery, 35.11±5.30 at 1 month after surgery, 25.22±4.85 at 3 months after surgery, and 6 months after surgery It was 16.78±4.63, and it was 10.91±2.36 after 12 months. The VAS score and ODI index of low back pain, lower limb pain at different time points after operation were significantly improved compared with that before operation (P<0.01). The effect of modified MacNab was excellent in 24 cases, good in 13 cases, and fair in 8 cases. The excellent and good rate was 82.22%. Among them, 1 patient developed femoral nerve palsy after endoscopic surgery, and was given a conservative treatment plan for neurotrophic therapy, acupuncture and moxibustion, and functional exercise. The symptoms disappeared 4 weeks after the operation. One patient developed neck and back pain during the operation and was considered as a class. The hypertension of the spinal cord was treated with removal of water pressure and oxygen inhalation, and the symptoms disappeared after 30 minutes. There were no serious surgical complications such as permanent nerve damage and intervertebral space infection in all cases. Conclusion : Percutaneous spinal endoscopic "isolation zone" technology through pedicle-flavum tunnel is a minimally invasive spinal surgery technique for the treatment of discogenic low back pain with safe operation and satisfactory clinical results. percutaneous spinal endoscopic discogenic low back pain isolation zone pedicle-flavum tunnel minimally invasive Figures Figure 1 Figure 2 1. Introduction Discogenic low back pain (DLBP) is a common type of spinal degenerative disease. It is the pain with or without leg pain and sometimes associated with sitting intolerance, an extension catch, diffificulty lifting, or an inability to maintain the same posture.The clinical symptoms of discogenic low back pain often occur repeatedly for a long time, causing great pain to patients, seriously affecting the quality of daily life and become a serious medical and social problem responsible for disability both in work and recreation[1, 2].The traditional treatment of discogenic low back pain is mainly conservative treatment (rest, drug treatment, physiotherapy, etc.), but it often can not fundamentally solve the problem of intervertebral disc annulus fibrosus tear[3]. For patients with ineffective conservative treatment, lumbar fusion surgery is often used to remove the degenerative intervertebral disc and stabilize the diseased segments, however, the traditional fusion surgery destroys the normal and stable structure of the spine, with high treatment cost and great surgical trauma, and the improvement of lumbar pain, spinal function and quality of life after fusion is not satisfactory[4] . Previous studies all adopted intradiscal technique, which belongs to Yeung endoscopic spine system(YESS) technique[5, 6]. The intradiscal radiofrequency therapy (PIRFT) and intradiscal electrothermal therapy (IDET) are also used in the treatment of DLBP[4, 7]. The treatment principle is to treat the annulus fibrosus fissure through intradiscal radiofrequency or high temperature, so as to destroy the pathway formed by inflammatory mediators in pain transmission, However, due to the limitation of puncture location, the postoperative effect of some patients is poor [8]. The endoscopic operation needs to first confirm the important anatomical structure "disc-flavum space", the nerve decompression can be carried out smoothly and orderly after the structure is clearly identified. Sensitive, especially prone to neurological damage during microscopic decompression. The concept of pedicle-flavum tunnel, a pathological structure of the spine, was first proposed by Xue Yuan et al. [9, 10]. It is a non-neural pathway that exists between the lateral side of the thoracic and lumbar ligamentum flavum or intervertebral disc and its adjacent upper and lower pedicles. Based on this background , the author used the "isolation zone" technique of lateral percutaneous endoscopic treatment of discogenic low back pain. This study retrospectively analyzed the clinical data of 45 patients with discogenic low back pain treated by spinal surgery in our hospital from September 2017 to September 2020, and discussed the surgical techniques and clinical effects of minimally invasive spinal endoscopy "isolation zone" technique through pedicle-flavum tunnel in the treatment of DLBP.The effect is summarized as follows. 2. Methods 2.1 Patient Demographics Of the 45 patients , age range 26~62, average (48.3±10.1) years. L4/5 29 cases, L5/S1 16 cases, case inclusion criteria :① There are low back and lumbosacral pain symptoms that affect daily life, without typical sciatic nerve pain. Prolonged sitting, standing, bending and physical labor can cause pain and discomfort in the lumbar back, hip, greater trochanter and groin, and the nature of pain is generally dull pain; ② Preoperative X-ray, CT, MRI and other imaging data showed single segment disc lesions, mostly mild herniation of intervertebral disc, no stenosis of bilateral lateral recess and no obvious collapse of intervertebral space. There was a high signal area of annulus fibrosus tear behind the responsible segment disc, and the MRI image showed hiz (high intensity zone)(Fig 2. a-b); ③ Physical examination showed no serious lower limb nerve dysfunction, and straight leg rising test was negative; ④ After strict conservative treatment, it is ineffective, and the symptoms seriously affect daily life and work; ⑤ Using the mixture of low concentration lidocaine and triamcinolone acetonide for intervertebral foramen responsible segmental nerve block, the visual analog scale (VAS) of pain decreased by more than 60% within 24 hours. Case exclusion criteria:1. Local segmental spinal instability or slippage ;2. Complicated with spinal tumor or myelopathy 3.Coagulation dysfunction 4. Complicated with mental disorders can not surgery. 2.2 Surgery Regular oral nonsteroidal anti-inflammatory analgesics (represented by diclofenac sodium), central skeletal muscle relaxants (represented by tizanidine hydrochloride) were administered 48 hours before operation. all patients underwent lateral position and performed the operation under the guidance of G arm X-ray machine. Local anesthesia (1% ropivacaine 10ml 2% lidocaine 30ml 0.9% saline 45ml) was used in all patients. The anesthesia levels were skin and subcutaneous, lumbar dorsal fascia, articular process joint and disc surface. All patients with discogenic low back pain use the pedicle-flavum tunnel "isolation zone" technique.The key technical points are:Intraoperative positioning of the puncture needle and placement of the endoscopic working channel through the pedicle-flavum tunnel without the passage of neurovascular，cleaning the inflammatory hyperplasia tissue on the surface of intervertebral disc and nerve root, sinus vertebral plexus block, cleaning and denervation of annulus fibrosus tear, removal of protruding nucleus pulposus tissue and intervertebral disc formation, denervation around the posterior longitudinal ligament, and forming an "isolation zone" of inflammatory factors and pain nerve conduction around nerve root and dura mater, To achieve the purpose of treating discogenic low back pain. Specific methods: The 18G puncture needle was used to puncture the bottom of the superior articular process of the target intervertebral space. The needle tip of the anterior and posterior X-ray fluoroscopy during the operation was located at the inner edge of the superior articular process, and the needle tip of the lateral X-ray fluoroscopy during the operation was located at the bottom of the superior articular process and protruded the lower edge of the intervertebral disc. Place the guide wire, cut the skin about 7 mm, place 2, 3.5, 4.5 and 5.5 mm catheters step by step to expand the soft tissue, place the Tom Shidi locator along the guide wire（Fig 1.a）, fix the tip of the Tom Shidi locator at the tip of the facet joint under fluoroscopy, point the tip to the protruding target of the intervertebral disc, gently hammer the bone penetrating the facet joint, appropriately adjust the depth of the Tom Shidi locator into the spinal canal according to the protruding position of the intervertebral disc（Fig 1.c-d）, and replace the guide wire after the positioning is confirmed by frontal and lateral fluoroscopy, Bone drills with diameters of 4.5, 6, 7, 8 and 9 mm（Fig 1.b） were successively inserted along the guide wire for intervertebral foramen plasty（Fig 1.e-f）. Replace the guide wire, insert the expansion guide rod, insert the 7.5mm working channel along the guide rod, and confirm that the working channel reaches the target through frontal and lateral fluoroscopy(Fig 2.c-d). The spinal endoscope was placed through the working channel. Through the central working channel of the 3.7 mm endoscope, the nucleus pulposus forceps were used to clean the local soft tissue and explore the tear of the annulus fibrosus. The red inflammatory soft tissue scattered on the surface and the nucleus pulposus tissue with severe degeneration and poor elasticity below were mainly cleaned, and the tear of the annulus fibrosus was removed with forceps. The flexible bipolar radiofrequency was used to denervate the edge of the fibrous ring and the interior of the intervertebral nucleus pulposus. The forceps were used to moderately remove some fibrous rings of the intervertebral disc to the proximal, caudal and contralateral sides. The removal range was that the proximal side could reach the posterior lower edge of the upper vertebral body, the caudal side could reach the posterior upper edge of the lower vertebral body, and the longitudinal fibers of the posterior longitudinal ligament could be exposed on the contralateral side. When there is sufficient space on the ventral side of the nerve root and the dural sac during the operation of the responsible segment, the edge and surface of the residual fibrous ring and the surface of the affected side of the posterior longitudinal ligament shall be electro coagulated and denervated by flexible bipolar radiofrequency. When the blood vessels on the surface of the nerve root are filled, there is autonomous pulsation, and the ventral and dorsal space is sufficient (Fig 2. e), after the subjective symptoms of the patient are reduced, the endoscope and working channel shall be withdrawn, and the incision shall be sutured. 2.3 Postoperative Management and Observation Index Postoperative routine administration of infection prevention, dehydration and detumescence, neurotrophic and corresponding symptomatic treatment.Get out of bed properly under the protection of waist orthosis or support on the first day after the operation（Waist orthosis or support protection for 3 weeks,get out of bed step by step），Guide patients to do lumbar dorsal muscle function exercise, straight leg raising（SLR）exercise and lumbar spine health care program daily.Regular follow-up, assess the patient's postoperative neurological improvement by the preoperative and postoperative different time points of back and lower extremity pain VAS score, dysfunction index (Oswestry disability index,ODI),at the last follow-up using improved Macnab criteria to evaluate the final clinical efficacy. 2.4 Statistical Analysis The data were analyzed by spss 22.0 statistical software(SPSS Inc, Chicago, IL). The measurement data were expressed by mean ± standard deviation (x ± s) are used to represent all the measurement data in this study，and the counting data are expressed as absolute number or rate (%). The comparison was made by ANOVA of repeated measurement data, Results were considered to be statistically signifificant if the P value was less than 0.05. 3. Results Clinical Outcomes Among the 45 patients, 1 had neck and back pain during the operation, which was considered as spinal cord like hyperbaric reaction. The symptoms disappeared 30 minutes after the removal of water pressure and oxygen inhalation. There was no forced interruption due to intolerable pain of local anesthesia. The operation time was 65~125 (94.7±17.7) min. The VAS score of lumbosacral pain was 6.95±1.02 before operation, 2.64±0.71 one month after operation, 1.80±0.54 three months after operation, 1.42±0.50 six months after operation and 1.27±0.45 12 months after operation; Oswsetry dysfunction index was 72.84±5.95 preoperatively, 35.1±5.30 one month postoperatively, 25.22±4.85 three months postoperatively, 16.78±4.63 six months postoperatively, and 10.91±2.36 12 months postoperatively. There was significant improvement compared with that before operation (p<0.01) (Table 1). At the last follow-up, the curative effect of modified macnab was excellent in 24 cases, good in 13 cases and fair in 8 cases. The excellent and good rate was 82.2% (Table 2). Postoperative reexamination of lumbar MRI showed that the tears of the fibrous ring at the responsible segment disappeared, and the "isolation area" at the ventral side of the dura mater and the ventral side of the nerve root healed well (Fig 2. f-i). Table 1 The VAS scores and Oswestry Disability Index(ODI)scores preoperatively and at each time point postoperatively Preoperative One month after operation Three months after operation Six months after operation Twelve months after operation VAS 6.95±1.02 2.64±0.71 ① 1.80±0.54 ① 1.42±0.50 ① 1.27±0.45 ① ODI 72.84±5.95 35.11±5.30 ① 25.22±4.85 ① 16.78±4.63 ① 10.91±2.36 ① Note：①Compared with preoperative, P＜0.01 Table 2 Evaluation of Modified MacNab Grading Standard after Operation excellent good fair Poor superior rate Total29cases 24 cases 13 cases 8 cases 0 cases 82.2% Complications One case of postoperative femoral nerve paralysis was treated conservatively with neuronutrition, acupuncture physiotherapy and functional exercise, and the symptoms disappeared 4 weeks after operation. There were no serious complications such as permanent nerve injury and intervertebral space infection. Discussion Discogenic low back pain is one of the common spinal degenerative diseases in clinic. It is mainly manifested in atypical low back pain and lower limb pain. The pain sites are mostly found in the lower waist, hip, hip and groin areas, posterolateral thigh and knee joints. The positioning is inaccurate. The symptoms will worsen when standing, sitting and bending for a long time[2, 11]. There is no typical sciatica, and the straight leg elevation test is mostly negative[12]. At present, it is believed that the pathogenesis of discogenic low back pain mainly includes the following points: ① local rupture of annulus fibrosus caused by intervertebral disc degeneration, and the production of inflammatory factors stimulates the pain receptors of sinus and vertebral nerves densely covered with intervertebral discs to cause pain[13]; ② The nerve endings proliferating in the nucleus pulposus at the annulus fibrosus gap induce lumbar pain under the combined action of nucleus pulposus pressure stimulation and inflammatory mediators[14]; ③ The central type of intervertebral disc herniation and fibrous ring tear squeeze the posterior longitudinal ligament and dural sac backward to form continuous stimulation of inflammatory media and form synergistic lumbar pain; ④ Due to the stimulation of inflammatory mediators, a large number of neovascularized pannus are formed in the area around the annulus fissuring, gradually forming scattered inflammatory lesions, aggravating the pain stimulation of new nerve fibers [15]. For discogenic low back pain, it is very necessary to determine the responsible segment. In addition to the lumbar MRI showing the signal change of the intervertebral disc with hiz and Modic signs and Schmorl nodules on the posterolateral side, discography, induction test and trans foraminal nerve block are important diagnostic techniques[16]. The angiography and induction test is to inject methylene blue into the intervertebral disc of the responsible segment[17]. During intervertebral disc imaging, methylene blue contrast agent flows out from the nucleus pulposus to the outer layer of the annulus fibrosus through the inner layer gap of the annulus fibrosus. The pressure generated by the contrast agent acts on the granulation tissue and the nerve fibers distributed therein, inducing the aggravation of lumbar pain, which is the basis for the replication of lumbar pain[18]. However, methylene blue is destructive to the normal intervertebral disc tissue[19]. In addition, False positive induction test will also lead to inaccurate preoperative judgment of responsible segments. Sometimes, it is necessary to make comparison of adjacent normal segments, which also increases the complexity of preoperative diagnosis[20]. Therefore, we prefer to use trans foraminal nerve drug block for preoperative diagnostic treatment. Under local infiltration anesthesia, the mixture of low concentration lidocaine and triamcinolone acetonide is injected into the lateral surface of the diseased intervertebral disc, and the analgesic effect is achieved by blocking the continuous nerve activity that produces pain. Trans foraminal nerve root block has high diagnostic value in discogenic low back pain. By confirming the responsible segment and observing the symptom relief, it is not only helpful to make a clear diagnosis, but also can provide a reference for the follow-up endoscopic treatment to a certain extent. Patients with discogenic low back pain can undergo segmental block surgery if their vas decreases by ≥ 60% within 24 hours after nerve root block via intervertebral foramen, otherwise it may be necessary to increase endoscopic decompression segments or change the treatment plan. The concept of the anatomical structure of the pedicle-flavum tunnel was first proposed by Xue Yuan et al[9, 10]. It is a neurovascular pathway that exists between the lateral side of the ligamentum flavum of the spine and its adjacent upper and lower pedicles. At first, this concept was applied to the ligamentum flavum of the thoracic spine. Surgical decompression therapy for spinal stenosis secondary to ossification[10], related studies have described a single-segment thoracic ligamentum flavum ossification of the ligamentum flavum through the nerve root channel, the octagonal free thoracic superior articular process and the ossified ligamentum flavum and surgery The method of posterior decompression of the thoracic spine after block resection[21]. Later, this anatomical pathway has also been applied to other parts of the spine such as the lumbar spine. The cause of the difficulty in microscopic treatment of discogenic low back pain is the adhesion and compression of the dorsal dura and nerve roots by the proliferating inflammatory soft tissue and herniated intervertebral disc. However, the areas of the superior and inferior pedicle-flavum tunnel formed between the anterior lateral superior border and posterior lateral inferior border of the herniated disc and the adjacent pedicles and dorsal ligamentum flavum belong to the anervous area and there is an appropriate operating space. Although there are many treatment schemes for discogenic low back pain, such as lumbar fusion surgery, intradiscal intervention technologies such as intradiscal electrotherapy, intradiscal injection of platelet rich plasma or hepatocytes, intradiscal ozone technology, etc., the above technologies are controversial at present, and the treatment results are often uncertain[22, 23]. On the basis of modern spinal endoscopy for the treatment of lumbar disc herniation, It is concluded that the "isolation zone" technique under spinal endoscopy can block or damage the main sensory nerve - sinus vertebral nerve, which is densely covered with pain conduction on the surface of the fibrous ring behind the intervertebral disc and the posterior longitudinal ligament, and comprehensively clean up the pathogenic inflammatory medium in the spinal canal and the intervertebral disc, so as to achieve a better clinical effect than the traditional image-guided or endoscopic minimally invasive treatment technique in the intervertebral disc[24]. Compared with the traditional spinal endoscopic nucleus pulposus removal, the details of this "isolation zone" technology in the treatment of discogenic low back pain are more complex than those of the traditional endoscopic discectomy. The technical requirements are to explore all the pain conducting nerve sinus vertebral nerve distribution areas, including the inflammatory tissue around the nerve root, the fibrous ring and the surface of the posterior longitudinal ligament, the intervertebral disc The whole running area of nerve root canal and the inflammatory tissue around the outlet nerve root. The "isolated area" spinal endoscopy technology used in this study has the following advantages in the treatment of discogenic low back pain: ① nerve block through the intervertebral foramen can accurately determine the responsible segment of discogenic low back pain, and avoid the damage to the intervertebral disc caused by the traditional intradiscal injection of contrast agent and the false-positive test; ② Endoscopic treatment of the responsible segment through the intervertebral foramen not only has less damage to the stable structure of the lumbar spine, but also preserves the spinal motor unit. It has advantages over the traditional fusion surgery in preventing the adjacent segment lesions after lumbar surgery; ③ Under local anesthesia, the patients can autonomously reflect the nerve function of the lower limbs during the operation. The risk of nerve injury is small, and the postoperative recovery is fast. They can exercise early; ④ The pathogenic factors of the responsible segments were comprehensively treated to achieve the purpose of treating discogenic low back pain. However, severe sinus and vertebral nerve stimulation may occur during the local anesthesia operation, and the complete establishment of the "isolation area" requires careful treatment of the soft tissue in the spinal canal, intervertebral disc, annulus fibrosus and posterior longitudinal ligament. The operator has high requirements for the technique of endoscopic operation. It is recommended to carry out the operation on the premise of good intraoperative pain management and mastering the technique of lateral intervertebral foraminal endoscopy. Conclusion On the basis of this study, the "isolation zone" technique through pedicle-flavum tunnel presents a safe and effective treatment for patients with DLBP during the early follow-up stage. Through a safe anatomical tunnel to make annuloplasty of the inflflammation and fully remove the pathogenic factors is the key point for a good result. Trans foraminal nerve root block has high diagnostic value for discogenic low back pain. By confirming the responsible segment and observing the symptom relief, it is not only helpful to make a clear diagnosis, but also can provide a reference for the follow-up endoscopic treatment to a certain extent. However, due to its study design and evidence level, a multicenter randomly study with larger amount cases and longer follow-up need to be conducted. Declarations Ethics approval and consent to participate The Ethics Committee of the Cangzhou central Hospital affifiliated to TianJin medical University approved this study (No. 20210205). All subjects provided informed consent to take part in the study. Consent for publication Written informed consent for publication was obtained from all participants. Competing Interests The authors declare that they have no competing interests. Author contributions Lu Wang performed the study. Cai Cheng and Yuan Xue conceived of the study and participated in its design. Lu Wang and Lingxia Li was responsible for coordination, data collection/ interpretation, and proofreading of the final manuscript. All authors read and approved the fnal manuscript. Funding This study was supported by the 2021 Hebei medical science research project plan of china(20210205) . Availability of data and materials The data and code used to support the fndings of this study are available from the corresponding author upon reasonable request. Acknowledgements Support from numerous colleagues, friends, and experts from Cangzhou central Hospital and Tianjin Medical University General Hospital is gratefully acknowledged. Author details 1 Department of Orthopedics,Cangzhou central hospital, Tianjin Medical University，Cangzhou, Hebei, China. 2 Department of clinical pharmacy, People's Hospital of Cangzhou City, Cangzhou, Hebei, China.3 Department of Orthopedics,Tianjin Medical University General Hospital,Tian jin ,China. References Zhang, Y.G., et al., Clinical diagnosis for discogenic low back pain. Int J Biol Sci, 2009. 5(7): p. 647-58. Kallewaard, J.W., et al., 15. Discogenic low back pain. Pain Pract, 2010. 10(6): p. 560-79. Peng, B., et al., Prospective clinical study on natural history of discogenic low back pain at 4 years of follow-up. 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Journal of neurological surgery. Part A, Central European neurosurgery, 2019. Zhang, X., et al., Clinical Evaluation and Magnetic Resonance Imaging Assessment of Intradiscal Methylene Blue Injection for the Treatment of Discogenic Low Back Pain. Pain Physician, 2016. 19(8): p. E1189-E1195. Yang, Z., et al., [Surgery tactics for ossification of ligamentum flavum associated with dural ossification in the thoracic spine]. Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi, 2012. 26(4): p. 401-5. Schneider, B.J., et al., The effectiveness of intradiscal biologic treatments for discogenic low back pain: a systematic review. Spine J, 2021. Bonetti, M., et al., Non-discogenic low back pain treated with oxygen-ozone: outcome in selected applications. J Biol Regul Homeost Agents, 2020. 34(4 Suppl. 1): p. 21-30. SPECIAL ISSUE: OZONE THERAPY. Manabe, H., et al., Thermal Annuloplasty Using Percutaneous Endoscopic Discectomy for Elite Athletes with Discogenic Low Back Pain. Neurol Med Chir (Tokyo), 2019. 59(2): p. 48-53. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-1761550","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":114217716,"identity":"94a1f6ea-30d4-4153-aa2d-af899337287f","order_by":0,"name":"lu wang","email":"","orcid":"","institution":"Cangzhou Central Hospital","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"lu","middleName":"","lastName":"wang","suffix":""},{"id":114217717,"identity":"dac14e77-49ab-4bfe-bd7e-12ad04e50d30","order_by":1,"name":"cai cheng","email":"","orcid":"","institution":"Cangzhou Central Hospital","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"cai","middleName":"","lastName":"cheng","suffix":""},{"id":114217718,"identity":"3ff1f408-3ed6-4f81-9281-12c449e820db","order_by":2,"name":"lingxia li","email":"","orcid":"","institution":"People's Hospital of Cangzhou","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"lingxia","middleName":"","lastName":"li","suffix":""},{"id":114217719,"identity":"7ef1ec83-e6e7-42de-8624-27a6cdbd8c9f","order_by":3,"name":"yuan xue","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA6UlEQVRIiWNgGAWjYBADOSA2ACIL4rUYQ7VIEK8lsQGshYEILQY3ko9J89TcSV/b3rx1w48CCQb+9u4Ehp87cGuRnJGWJs1z7FnutjPHym72AB0mcebsBsbeM7i18EvkmEnzsB3O3XYjx+wGD1CLgUTuBmbGNtxa2CTyv0nz/Ducbnb/jdnNP8RoAdrCJs3bdjgBaIXZbaJskex5Zmw5t++w4bYzaWW3ZQwkeEB+OdiLR4vB8eSHN958Oyxvdvzwtptv/tjI8bf3bnzwE48WIGBBiQseEHEArwYGBuYPBBSMglEwCkbBSAcAG1tQG467zMQAAAAASUVORK5CYII=","orcid":"","institution":"Tianjin Medical University General Hospital","correspondingAuthor":true,"submittingAuthor":false,"prefix":"","firstName":"yuan","middleName":"","lastName":"xue","suffix":""}],"badges":[],"createdAt":"2022-06-15 13:59:08","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-1761550/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-1761550/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":22961559,"identity":"2a409353-42d4-4802-9552-54411a595ca4","added_by":"auto","created_at":"2022-06-22 18:43:39","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":769321,"visible":true,"origin":"","legend":"\u003cp\u003e\u0026nbsp;a: Tom shidi locator and combined with guide wire;\u0026nbsp;b:\u0026nbsp;Bone drill and combined with guide wire ;\u0026nbsp;c: Intraoperative lateral X-ray of Tom shidi locator;\u0026nbsp;d: Intraoperative AP X-ray of Tom shidi locator;\u0026nbsp;e:\u0026nbsp;Intraoperative lateral X-ray of bone drill. f： Intraoperative AP X-ray of bone drill.\u003c/p\u003e","description":"","filename":"Figure1.png","url":"https://assets-eu.researchsquare.com/files/rs-1761550/v1/a0969b77e466da5f385d9ef1.png"},{"id":22962371,"identity":"fecd5ac0-322e-46e5-a299-804855ed883b","added_by":"auto","created_at":"2022-06-22 18:48:39","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":677655,"visible":true,"origin":"","legend":"\u003cp\u003ea-b: High intensity zone of L4 / 5 segment intervertebral disc annulus fibrosus can be seen in the\u0026nbsp;preoperative lumbar MRI;\u0026nbsp;c-d: The working channel of spinal endoscopy during operation ; Figure e: Intraoperative images showed the \"isolation area\" formed in the nerve root and ventral dura after endoscopic decompression;\u0026nbsp;f-g: One week after operation, the lumbar MRI was rechecked, and the signal of fibrillar ring tear disappeared;the range of ventral decompression of dura mater was sufficient;\u0026nbsp;h-i: The lumbar MRI was reexamined 10 months after operation, the tear of fibrous ring disappeared; the surgical scope of \"isolation area\" healed well.\u003c/p\u003e\u003cp\u003eComplications\u003c/p\u003e\u003cp\u003e\u003cbr\u003e\u003c/p\u003e","description":"","filename":"Figure2.png","url":"https://assets-eu.researchsquare.com/files/rs-1761550/v1/c3103e9288e8f7374e0256a8.png"},{"id":32964646,"identity":"98b59fde-f756-4d4c-a3ca-4ee58262a900","added_by":"auto","created_at":"2023-02-15 08:44:33","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1659948,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-1761550/v1/a885e5b8-9f3b-4341-b07c-2f2660f4650d.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"\u003cp\u003eClinical study on the treatment of discogenic low back pain by endoscopic \"isolation zone\" technique through pedicle-flavum tunnel\u003c/p\u003e","fulltext":[{"header":"1. Introduction","content":"\u003cp\u003eDiscogenic low back pain (DLBP) is a common type of spinal degenerative disease. It is the pain with or without leg pain and sometimes associated with sitting intolerance, an extension catch, diffificulty lifting, or an inability to maintain the same posture.The clinical symptoms of discogenic low back pain often occur repeatedly for a long time, causing great pain to patients, seriously affecting the quality of daily life and become a serious medical and social problem responsible for disability both in work and recreation[1, 2].The traditional treatment of discogenic low back pain is mainly conservative treatment (rest, drug treatment, physiotherapy, etc.), but it often can not fundamentally solve the problem of intervertebral disc annulus fibrosus tear[3].\u003c/p\u003e\n\u003cp\u003eFor patients with ineffective conservative treatment, lumbar fusion surgery is often used to remove the degenerative intervertebral disc and stabilize the diseased segments, however, the traditional fusion surgery destroys the normal and stable structure of the spine, with high treatment cost and great surgical trauma, and the improvement of lumbar pain, spinal function and quality of life after fusion is not satisfactory[4]\u0026nbsp;.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003ePrevious studies all adopted intradiscal technique, which belongs to Yeung endoscopic spine system(YESS) technique[5, 6]. The intradiscal radiofrequency therapy (PIRFT) and intradiscal electrothermal therapy (IDET) are also used in the treatment of DLBP[4, 7]. The treatment principle is to treat the annulus fibrosus fissure through intradiscal radiofrequency or high temperature, so as to destroy the pathway formed by inflammatory mediators in pain transmission, However, due to the limitation of puncture location, the postoperative effect of some patients is poor\u0026nbsp;[8].\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe endoscopic operation needs to first confirm the important anatomical structure \u0026quot;disc-flavum\u0026nbsp;space\u0026quot;, the nerve decompression can be carried out smoothly and orderly after the structure is clearly identified. Sensitive, especially prone to neurological damage during microscopic decompression. The concept of\u0026nbsp;pedicle-flavum tunnel, a pathological structure of the spine, was first proposed by Xue Yuan et al.\u0026nbsp;[9, 10]. It is a non-neural pathway that exists between the lateral side of the thoracic and lumbar ligamentum flavum or intervertebral disc and its adjacent upper and lower pedicles. Based on this background , the author used the \u0026quot;isolation zone\u0026quot; technique of lateral percutaneous endoscopic treatment of discogenic low back pain.\u003c/p\u003e\n\u003cp\u003eThis study retrospectively analyzed the clinical data of 45 patients with discogenic low back pain treated by spinal surgery in our hospital from September 2017 to September 2020, and discussed the surgical techniques and clinical effects of minimally invasive spinal endoscopy \u0026quot;isolation zone\u0026quot; technique through pedicle-flavum tunnel in the treatment of DLBP.The effect is summarized as follows.\u003c/p\u003e"},{"header":"2. Methods","content":"\u003cp\u003e\u003cstrong\u003e\u003cem\u003e2.1 Patient\u0026nbsp;Demographics\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eOf the 45 patients , age range 26~62, average (48.3\u0026plusmn;10.1) years. L4/5 29 cases, L5/S1 16 cases, case inclusion criteria :① There are low back and lumbosacral pain symptoms that affect daily life, without typical sciatic nerve pain. Prolonged sitting, standing, bending and physical labor can cause pain and discomfort in the lumbar back, hip, greater trochanter and groin, and the nature of pain is generally dull pain; ② Preoperative X-ray, CT, MRI and other imaging data showed single segment disc lesions, mostly mild herniation of intervertebral disc, no stenosis of bilateral lateral recess and no obvious collapse of intervertebral space. There was a high signal area of annulus fibrosus tear behind the responsible segment disc, and the MRI image showed hiz (high intensity zone)(Fig 2. a-b); ③ Physical examination showed no serious lower limb nerve dysfunction, and straight leg rising test was negative; ④ After strict conservative treatment, it is ineffective, and the symptoms seriously affect daily life and work; ⑤ Using the mixture of low concentration lidocaine and triamcinolone acetonide for intervertebral foramen responsible segmental nerve block, the visual analog scale (VAS) of pain decreased by more than 60% within 24 hours.\u003c/p\u003e\n\u003cp\u003eCase exclusion criteria:1. Local segmental spinal instability or slippage ;2. Complicated with spinal tumor or myelopathy 3.Coagulation dysfunction 4. Complicated with mental disorders can not surgery.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003e2.2 Surgery\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eRegular oral nonsteroidal anti-inflammatory analgesics (represented by diclofenac sodium), central skeletal muscle relaxants (represented by tizanidine hydrochloride) were administered 48 hours before operation. all patients underwent lateral position and performed the operation under the guidance of G arm X-ray machine.\u003c/p\u003e\n\u003cp\u003eLocal anesthesia (1% ropivacaine 10ml 2% lidocaine 30ml 0.9% saline 45ml) was used in all patients. The anesthesia levels were skin and subcutaneous, lumbar dorsal fascia, articular process joint and disc surface.\u003c/p\u003e\n\u003cp\u003eAll patients with discogenic low back pain use the\u0026nbsp;pedicle-flavum tunnel\u0026nbsp;\u0026quot;isolation zone\u0026quot; technique.The key technical points are:Intraoperative positioning of the puncture needle and placement of the endoscopic working channel through the\u0026nbsp;pedicle-flavum tunnel\u0026nbsp;without the passage of neurovascular，cleaning the inflammatory hyperplasia tissue on the surface of intervertebral disc and nerve root, sinus vertebral plexus block, cleaning and denervation of annulus fibrosus tear, removal of protruding nucleus pulposus tissue and intervertebral disc formation, denervation around the posterior longitudinal ligament, and forming an \u0026quot;isolation zone\u0026quot; of inflammatory factors and pain nerve conduction around nerve root and dura mater, To achieve the purpose of treating discogenic low back pain.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eSpecific methods: The 18G puncture needle was used to puncture the bottom of the superior articular process of the target intervertebral space. The needle tip of the anterior and posterior X-ray fluoroscopy during the operation was located at the inner edge of the superior articular process, and the needle tip of the lateral X-ray fluoroscopy during the operation was located at the bottom of the superior articular process and protruded the lower edge of the intervertebral disc. Place the guide wire, cut the skin about 7 mm, place 2, 3.5, 4.5 and 5.5 mm catheters step by step to expand the soft tissue, place the Tom Shidi\u0026nbsp;locator\u0026nbsp;along the guide wire（Fig 1.a）, fix the tip of the Tom Shidi\u0026nbsp;locator\u0026nbsp;at the tip of the facet joint under fluoroscopy, point the tip to the protruding target of the intervertebral disc, gently hammer the bone penetrating the facet joint, appropriately adjust the depth of the Tom Shidi\u0026nbsp;locator\u0026nbsp;into the spinal canal according to the protruding position of the intervertebral disc（Fig 1.c-d）, and replace the guide wire after the positioning is confirmed by frontal and lateral fluoroscopy, Bone drills with diameters of 4.5, 6, 7, 8 and 9 mm（Fig 1.b）\u0026nbsp;were successively inserted along the guide wire for intervertebral foramen plasty（Fig 1.e-f）. Replace the guide wire, insert the expansion guide rod, insert the 7.5mm working channel along the guide rod, and confirm that the working channel reaches the target through frontal and lateral fluoroscopy(Fig 2.c-d). The spinal endoscope was placed through the working channel. Through the central working channel of the 3.7 mm endoscope, the nucleus pulposus forceps were used to clean the local soft tissue and explore the tear of the annulus fibrosus. The red inflammatory soft tissue scattered on the surface and the nucleus pulposus tissue with severe degeneration and poor elasticity below were mainly cleaned, and the tear of the annulus fibrosus was removed with forceps. The flexible bipolar radiofrequency was used to denervate the edge of the fibrous ring and the interior of the intervertebral nucleus pulposus. The forceps were used to moderately remove some fibrous rings of the intervertebral disc to the proximal, caudal and contralateral sides. The removal range was that the proximal side could reach the posterior lower edge of the upper vertebral body, the caudal side could reach the posterior upper edge of the lower vertebral body, and the longitudinal fibers of the posterior longitudinal ligament could be exposed on the contralateral side. When there is sufficient space on the ventral side of the nerve root and the dural sac during the operation of the responsible segment, the edge and surface of the residual fibrous ring and the surface of the affected side of the posterior longitudinal ligament shall be electro coagulated and denervated by flexible bipolar radiofrequency. When the blood vessels on the surface of the nerve root are filled, there is autonomous pulsation, and the ventral and dorsal space is sufficient\u0026nbsp;(Fig 2. e), after the subjective symptoms of the patient are reduced, the endoscope and working channel shall be withdrawn, and the incision shall be sutured.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003e2.3\u0026nbsp;Postoperative\u0026nbsp;Management and\u0026nbsp;Observation\u0026nbsp;Index\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003ePostoperative routine administration of infection prevention, dehydration and detumescence, neurotrophic and corresponding symptomatic treatment.Get out of bed properly under the protection of waist orthosis or support on the first day after the operation（Waist orthosis or support protection for 3 weeks,get out of bed step by step），Guide patients to do lumbar dorsal muscle function exercise, straight leg raising（SLR）exercise and lumbar spine health care program daily.Regular follow-up, assess the patient\u0026apos;s postoperative neurological improvement by the preoperative and postoperative different time points of back and lower extremity pain VAS score, dysfunction index (Oswestry disability index,ODI),at the last follow-up using improved Macnab criteria to evaluate the final clinical efficacy.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003e2.4 Statistical Analysis\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe data were analyzed by spss 22.0 statistical software(SPSS Inc, Chicago, IL). The measurement data were expressed by mean \u0026plusmn; standard deviation (x \u0026plusmn; s) are used to represent all the measurement data in this study，and the counting data are expressed as absolute number or rate (%). The comparison was made by ANOVA of repeated measurement data, Results were considered to be statistically signifificant if the P value was less than 0.05.\u003c/p\u003e"},{"header":"3. Results","content":"\u003cp\u003e\u003cstrong\u003e\u003cem\u003eClinical Outcomes\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAmong the 45 patients, 1 had neck and back pain during the operation, which was considered as spinal cord like hyperbaric reaction. The symptoms disappeared 30 minutes after the removal of water pressure and oxygen inhalation. There was no forced interruption due to intolerable pain of local anesthesia. The operation time was 65~125 (94.7\u0026plusmn;17.7) min. The VAS score of lumbosacral pain was 6.95\u0026plusmn;1.02 before operation, 2.64\u0026plusmn;0.71 one month after operation, 1.80\u0026plusmn;0.54 three months after operation, 1.42\u0026plusmn;0.50 six months after operation and 1.27\u0026plusmn;0.45 12 months after operation; Oswsetry dysfunction index was 72.84\u0026plusmn;5.95 preoperatively, 35.1\u0026plusmn;5.30 one month postoperatively, 25.22\u0026plusmn;4.85 three months postoperatively, 16.78\u0026plusmn;4.63 six months postoperatively, and 10.91\u0026plusmn;2.36 12 months postoperatively. There was significant improvement compared with that before operation (p\u0026lt;0.01) (Table 1). At the last follow-up, the curative effect of modified macnab was excellent in 24 cases, good in 13 cases and fair in 8 cases. The excellent and good rate was 82.2% (Table 2). Postoperative reexamination of lumbar MRI showed that the tears of the fibrous ring at the responsible segment disappeared, and the \u0026quot;isolation area\u0026quot; at the ventral side of the dura mater and the ventral side of the nerve root healed well (Fig 2. f-i).\u003c/p\u003e\n\u003cp\u003eTable 1 The VAS scores and Oswestry Disability Index(ODI)scores preoperatively and at each time point postoperatively\u003c/p\u003e\n\u003ctable border=\"1\" cellpadding=\"0\" cellspacing=\"0\" width=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"7.176287051482059%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" width=\"14.820592823712948%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003ePreoperative\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"18.720748829953198%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eOne month after operation\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"19.81279251170047%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eThree months after operation\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"18.252730109204368%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eSix months after operation\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" width=\"21.21684867394696%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eTwelve months after operation\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"7.176287051482059%\"\u003e\n \u003cp\u003eVAS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" width=\"14.820592823712948%\"\u003e\n \u003cp\u003e6.95\u0026plusmn;1.02\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"18.720748829953198%\"\u003e\n \u003cp\u003e2.64\u0026plusmn;0.71\u003csup\u003e①\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"19.81279251170047%\"\u003e\n \u003cp\u003e1.80\u0026plusmn;0.54\u003csup\u003e①\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"18.252730109204368%\"\u003e\n \u003cp\u003e1.42\u0026plusmn;0.50\u003csup\u003e①\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" width=\"21.21684867394696%\"\u003e\n \u003cp\u003e1.27\u0026plusmn;0.45\u003csup\u003e①\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"7.165109034267913%\"\u003e\n \u003cp\u003eODI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.330218068535826%\"\u003e\n \u003cp\u003e72.84\u0026plusmn;5.95\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" width=\"19.1588785046729%\"\u003e\n \u003cp\u003e35.11\u0026plusmn;5.30\u003csup\u003e①\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"19.781931464174455%\"\u003e\n \u003cp\u003e25.22\u0026plusmn;4.85\u003csup\u003e①\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" width=\"18.53582554517134%\"\u003e\n \u003cp\u003e16.78\u0026plusmn;4.63\u003csup\u003e①\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"21.02803738317757%\"\u003e\n \u003cp\u003e10.91\u0026plusmn;2.36\u003csup\u003e①\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eNote：①Compared with preoperative, P＜0.01\u003c/p\u003e\n\u003cp\u003eTable 2 Evaluation of Modified MacNab Grading Standard after Operation\u003c/p\u003e\n\u003ctable border=\"1\" cellpadding=\"0\" cellspacing=\"0\" width=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"15.978456014362656%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"16.51705565529623%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eexcellent\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"15.978456014362656%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003egood\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"16.337522441651707%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003efair\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"15.978456014362656%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003ePoor\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"19.210053859964095%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003esuperior\u0026nbsp;rate\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"15.978456014362656%\"\u003e\n \u003cp\u003eTotal29cases\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"16.51705565529623%\"\u003e\n \u003cp\u003e24 cases\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"15.978456014362656%\"\u003e\n \u003cp\u003e13 cases\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"16.337522441651707%\"\u003e\n \u003cp\u003e8 cases\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"15.978456014362656%\"\u003e\n \u003cp\u003e0 cases\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"19.210053859964095%\"\u003e\n \u003cp\u003e82.2%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eComplications\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eOne case of postoperative femoral nerve paralysis was treated conservatively with neuronutrition, acupuncture physiotherapy and functional exercise, and the symptoms disappeared 4 weeks after operation. There were no serious complications such as permanent nerve injury and intervertebral space infection.\u0026nbsp;\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eDiscogenic low back pain is one of the common spinal degenerative diseases in clinic. It is mainly manifested in atypical low back pain and lower limb pain. The pain sites are mostly found in the lower waist, hip, hip and groin areas, posterolateral thigh and knee joints. The positioning is inaccurate. The symptoms will worsen when standing, sitting and bending for a long time[2, 11]. There is no typical sciatica, and the straight leg elevation test is mostly negative[12]. At present, it is believed that the pathogenesis of discogenic low back pain mainly includes the following points: ① local rupture of annulus fibrosus caused by intervertebral disc degeneration, and the production of inflammatory factors stimulates the pain receptors of sinus and vertebral nerves densely covered with intervertebral discs to cause pain[13]; ② The nerve endings proliferating in the nucleus pulposus at the annulus fibrosus gap induce lumbar pain under the combined action of nucleus pulposus pressure stimulation and inflammatory mediators[14]; ③ The central type of intervertebral disc herniation and fibrous ring tear squeeze the posterior longitudinal ligament and dural sac backward to form continuous stimulation of inflammatory media and form synergistic lumbar pain; ④ Due to the stimulation of inflammatory mediators, a large number of neovascularized pannus are formed in the area around the annulus fissuring, gradually forming scattered inflammatory lesions, aggravating the pain stimulation of new nerve fibers\u0026nbsp;[15].\u003c/p\u003e\n\u003cp\u003eFor discogenic low back pain, it is very necessary to determine the responsible segment. In addition to the lumbar MRI showing the signal change of the intervertebral disc with hiz and Modic signs and Schmorl nodules on the posterolateral side, discography, induction test and trans foraminal nerve block are important diagnostic techniques[16]. The angiography and induction test is to inject methylene blue into the intervertebral disc of the responsible segment[17]. During intervertebral disc imaging, methylene blue contrast agent flows out from the nucleus pulposus to the outer layer of the annulus fibrosus through the inner layer gap of the annulus fibrosus. The pressure generated by the contrast agent acts on the granulation tissue and the nerve fibers distributed therein, inducing the aggravation of lumbar pain, which is the basis for the replication of lumbar pain[18]. However, methylene blue is destructive to the normal intervertebral disc tissue[19]. In addition, False positive induction test will also lead to inaccurate preoperative judgment of responsible segments. Sometimes, it is necessary to make comparison of adjacent normal segments, which also increases the complexity of preoperative diagnosis[20]. Therefore, we prefer to use trans foraminal nerve drug block for preoperative diagnostic treatment. Under local infiltration anesthesia, the mixture of low concentration lidocaine and triamcinolone acetonide is injected into the lateral surface of the diseased intervertebral disc, and the analgesic effect is achieved by blocking the continuous nerve activity that produces pain. Trans foraminal nerve root block has high diagnostic value in discogenic low back pain. By confirming the responsible segment and observing the symptom relief, it is not only helpful to make a clear diagnosis, but also can provide a reference for the follow-up endoscopic treatment to a certain extent. Patients with discogenic low back pain can undergo segmental block surgery if their vas decreases by \u0026ge; 60% within 24 hours after nerve root block via intervertebral foramen, otherwise it may be necessary to increase endoscopic decompression segments or change the treatment plan.\u003c/p\u003e\n\u003cp\u003eThe concept of the anatomical structure of the pedicle-flavum tunnel was first proposed by Xue Yuan et al[9, 10]. It is a neurovascular pathway that exists between the lateral side of the ligamentum flavum of the spine and its adjacent upper and lower pedicles. At first, this concept was applied to the ligamentum flavum of the thoracic spine. Surgical decompression therapy for spinal stenosis secondary to ossification[10], related studies have described a single-segment thoracic ligamentum flavum ossification of the ligamentum flavum through the nerve root channel, the octagonal free thoracic superior articular process and the ossified ligamentum flavum and surgery The method of posterior decompression of the thoracic spine after block resection[21]. Later, this anatomical pathway has also been applied to other parts of the spine such as the lumbar spine. The cause of the difficulty in microscopic treatment of discogenic low back pain is the adhesion and compression of the dorsal dura and nerve roots by the proliferating inflammatory soft tissue and herniated intervertebral disc. However, the areas of the superior and inferior pedicle-flavum tunnel formed between the anterior lateral superior border and posterior lateral inferior border of the herniated disc and the adjacent pedicles and dorsal ligamentum flavum belong to the anervous area and there is an appropriate operating space.\u003c/p\u003e\n\u003cp\u003eAlthough there are many treatment schemes for discogenic low back pain, such as lumbar fusion surgery, intradiscal intervention technologies such as intradiscal electrotherapy, intradiscal injection of platelet rich plasma or hepatocytes, intradiscal ozone technology, etc., the above technologies are controversial at present, and the treatment results are often uncertain[22, 23]. On the basis of modern spinal endoscopy for the treatment of lumbar disc herniation, It is concluded that the \u0026quot;isolation zone\u0026quot; technique under spinal endoscopy can block or damage the main sensory nerve - sinus vertebral nerve, which is densely covered with pain conduction on the surface of the fibrous ring behind the intervertebral disc and the posterior longitudinal ligament, and comprehensively clean up the pathogenic inflammatory medium in the spinal canal and the intervertebral disc, so as to achieve a better clinical effect than the traditional image-guided or endoscopic minimally invasive treatment technique in the intervertebral disc[24]. Compared with the traditional spinal endoscopic nucleus pulposus removal, the details of this \u0026quot;isolation zone\u0026quot; technology in the treatment of discogenic low back pain are more complex than those of the traditional endoscopic discectomy. The technical requirements are to explore all the pain conducting nerve sinus vertebral nerve distribution areas, including the inflammatory tissue around the nerve root, the fibrous ring and the surface of the posterior longitudinal ligament, the intervertebral disc The whole running area of nerve root canal and the inflammatory tissue around the outlet nerve root.\u003c/p\u003e\n\u003cp\u003eThe \u0026quot;isolated area\u0026quot; spinal endoscopy technology used in this study has the following advantages in the treatment of discogenic low back pain: ① nerve block through the intervertebral foramen can accurately determine the responsible segment of discogenic low back pain, and avoid the damage to the intervertebral disc caused by the traditional intradiscal injection of contrast agent and the false-positive test; ② Endoscopic treatment of the responsible segment through the intervertebral foramen not only has less damage to the stable structure of the lumbar spine, but also preserves the spinal motor unit. It has advantages over the traditional fusion surgery in preventing the adjacent segment lesions after lumbar surgery; ③ Under local anesthesia, the patients can autonomously reflect the nerve function of the lower limbs during the operation. The risk of nerve injury is small, and the postoperative recovery is fast. They can exercise early; ④ The pathogenic factors of the responsible segments were comprehensively treated to achieve the purpose of treating discogenic low back pain.\u003c/p\u003e\n\u003cp\u003eHowever, severe sinus and vertebral nerve stimulation may occur during the local anesthesia operation, and the complete establishment of the \u0026quot;isolation area\u0026quot; requires careful treatment of the soft tissue in the spinal canal, intervertebral disc, annulus fibrosus and posterior longitudinal ligament. The operator has high requirements for the technique of endoscopic operation. It is recommended to carry out the operation on the premise of good intraoperative pain management and mastering the technique of lateral intervertebral foraminal endoscopy.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eOn the basis of this study, the \u0026quot;isolation zone\u0026quot; technique through pedicle-flavum tunnel presents a safe and effective treatment for patients with DLBP during the early \u0026nbsp;follow-up stage. Through a safe anatomical tunnel to make annuloplasty of the inflflammation and fully remove the pathogenic factors is the key point for a good result. Trans foraminal nerve root block has high diagnostic value for discogenic low back pain. By confirming the responsible segment and observing the symptom relief, it is not only helpful to make a clear diagnosis, but also can provide a reference for the follow-up endoscopic treatment to a certain extent. However, due to its study design and evidence level, a multicenter randomly study with larger amount cases and longer follow-up need to be conducted.\u003c/p\u003e\n"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003eThe Ethics Committee of the\u0026nbsp;Cangzhou central Hospital affifiliated to TianJin medical University\u0026nbsp;approved this study (No.\u0026nbsp;20210205). All subjects provided informed consent to take part in the study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003eWritten informed consent for publication was obtained from all participants.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting Interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eLu Wang\u0026nbsp;\u003c/strong\u003eperformed the study. Cai Cheng and Yuan Xue conceived of the study and participated in its design.\u0026nbsp;\u003cstrong\u003eLu Wang and\u0026nbsp;\u003c/strong\u003eLingxia Li was responsible for coordination, data collection/ interpretation, and proofreading of the final manuscript. All authors read and approved the fnal manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was supported by the 2021 Hebei medical science research project plan of china(20210205) .\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003eThe data and code used to support the fndings of this study are available from the corresponding author upon reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eSupport from numerous colleagues, friends, and experts from\u0026nbsp;Cangzhou central Hospital and\u0026nbsp;Tianjin Medical University General Hospital\u0026nbsp;is gratefully acknowledged.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor details\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e1 Department of Orthopedics,Cangzhou central hospital, Tianjin Medical University，Cangzhou, Hebei, China. 2 Department of clinical pharmacy, People\u0026apos;s Hospital of Cangzhou City, Cangzhou, Hebei, China.3 Department of Orthopedics,Tianjin Medical University General Hospital,Tian jin ,China.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n \u003cli\u003eZhang, Y.G., et al., Clinical diagnosis for discogenic low back pain. Int J Biol Sci, 2009. 5(7): p. 647-58.\u003c/li\u003e\n \u003cli\u003eKallewaard, J.W., et al., 15. Discogenic low back pain. Pain Pract, 2010. 10(6): p. 560-79.\u003c/li\u003e\n \u003cli\u003ePeng, B., et al., Prospective clinical study on natural history of discogenic low back pain at 4 years of follow-up. Pain Physician, 2012. 15(6): p. 525-32.\u003c/li\u003e\n \u003cli\u003eAndersson, G.B., N.A. Mekhail and J.E. Block, Treatment of intractable discogenic low back pain. A systematic review of spinal fusion and intradiscal electrothermal therapy (IDET). Pain Physician, 2006. 9(3): p. 237-48.\u003c/li\u003e\n \u003cli\u003eYeung, A.T., Foreword, Percutaneous and Endoscopic MIS Special Issue. Int J Spine Surg, 2014. 8.\u003c/li\u003e\n \u003cli\u003eTsou, P.M., Y.C. Alan and A.T. Yeung, Posterolateral transforaminal selective endoscopic discectomy and thermal annuloplasty for chronic lumbar discogenic pain: a minimal access visualized intradiscal surgical procedure. Spine J, 2004. 4(5): p. 564-73.\u003c/li\u003e\n \u003cli\u003eUrrutia, G., et al., Percutaneous thermocoagulation intradiscal techniques for discogenic low back pain. Spine (Phila Pa 1976), 2007. 32(10): p. 1146-54.\u003c/li\u003e\n \u003cli\u003eBono, C.M., et al., Pain intensity and patients\u0026apos; acceptance of surgical complication risks with lumbar fusion. Spine (Phila Pa 1976), 2013. 38(2): p. 140-7.\u003c/li\u003e\n \u003cli\u003eZhao, Y., et al., The CT and intraoperative observation of pedicel-ossification tunnel in 151 cases of thoracic spinal stenosis from ossification of ligamentum flavum. Eur Spine J, 2014. 23(6): p. 1325-31.\u003c/li\u003e\n \u003cli\u003eYang, Z., et al., Upper facet joint en bloc resection for the treatment of thoracic myelopathy caused by ossification of the ligamentum flavum. J Neurosurg Spine, 2013. 19(1): p. 81-9.\u003c/li\u003e\n \u003cli\u003eTonosu, J., et al., Diagnosing Discogenic Low Back Pain Associated with Degenerative Disc Disease Using a Medical Interview. PLoS One, 2016. 11(11): p. e0166031.\u003c/li\u003e\n \u003cli\u003eSimon, J., et al., Discogenic low back pain. Phys Med Rehabil Clin N Am, 2014. 25(2): p. 305-17.\u003c/li\u003e\n \u003cli\u003eMinamide, A., et al., Microendoscopic Decompression for Lumbar Spinal Stenosis With Degenerative Spondylolisthesis: The Influence of Spondylolisthesis Stage (Disc Height and Static and Dynamic Translation) on Clinical Outcomes. Clin Spine Surg, 2019. 32(1): p. E20-E26.\u003c/li\u003e\n \u003cli\u003eYeung, A.T. and C.A. Yeung, In-vivo endoscopic visualization of patho-anatomy in painful degenerative conditions of the lumbar spine. Surg Technol Int, 2006. 15: p. 243-56.\u003c/li\u003e\n \u003cli\u003eShi, C., et al., Development of an in vivo mouse model of discogenic low back pain. J Cell Physiol, 2018. 233(10): p. 6589-6602.\u003c/li\u003e\n \u003cli\u003eCurtis, W.S., et al., Nonsurgical treatment for radicular of pain of zygoapophyseal joint cyst origin: Therapeutic selective nerve root block. Archives of Physical Medicine and Rehabilitation, 2000. 81(8).\u003c/li\u003e\n \u003cli\u003eGupta, G., et al., Methylene blue in the treatment of discogenic low back pain. Pain Physician, 2012. 15(4): p. 333-8.\u003c/li\u003e\n \u003cli\u003eKallewaard, J.W., et al., A multicenter randomized controlled trial on the efficacy of intradiscal methylene blue injection for chronic discogenic low back pain: the IMBI study. Pain, 2019. 160(4): p. 945-953.\u003c/li\u003e\n \u003cli\u003eWang, X., et al., Deleterious Effects of Methylene Blue on Rat Nucleus Pulposus Cell in Vitro: Changes in Cell Viability and Secretory Phenotype in Exposed Cells. Journal of neurological surgery. Part A, Central European neurosurgery, 2019.\u003c/li\u003e\n \u003cli\u003eZhang, X., et al., Clinical Evaluation and Magnetic Resonance Imaging Assessment of Intradiscal Methylene Blue Injection for the Treatment of Discogenic Low Back Pain. Pain Physician, 2016. 19(8): p. E1189-E1195.\u003c/li\u003e\n \u003cli\u003eYang, Z., et al., [Surgery tactics for ossification of ligamentum flavum associated with dural ossification in the thoracic spine]. Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi, 2012. 26(4): p. 401-5.\u003c/li\u003e\n \u003cli\u003eSchneider, B.J., et al., The effectiveness of intradiscal biologic treatments for discogenic low back pain: a systematic review. Spine J, 2021.\u003c/li\u003e\n \u003cli\u003eBonetti, M., et al., Non-discogenic low back pain treated with oxygen-ozone: outcome in selected applications. J Biol Regul Homeost Agents, 2020. 34(4 Suppl. 1): p. 21-30. SPECIAL ISSUE: OZONE THERAPY.\u003c/li\u003e\n \u003cli\u003eManabe, H., et al., Thermal Annuloplasty Using Percutaneous Endoscopic Discectomy for Elite Athletes with Discogenic Low Back Pain. Neurol Med Chir (Tokyo), 2019. 59(2): p. 48-53.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"percutaneous spinal endoscopic, discogenic low back pain, isolation zone, pedicle-flavum tunnel, minimally invasive","lastPublishedDoi":"10.21203/rs.3.rs-1761550/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-1761550/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eObjective\u003c/strong\u003e: To explore the surgical strategy and clinical effects of the \"isolation zone\" technique through pedicle-flavum tunnel for the treatment of discogenic low back pain under percutaneous spinal endoscopy.\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eMethods\u003c/strong\u003e: From September 2017 to September 2020, the author treated patients with intervertebral discogenic low back pain with lateral approach percutaneous spinal endoscopic surgery under local anesthesia. The working channel is inserted through the anatomical pedicle-flavum tunnel and performed neuralization and corresponding segmental nerve roots are decompressed throughout the process, forming an \"isolation zone\" around the nerve root without contact with the nucleus pulposus and annulus fibrosus. The visual analogue scale (Visual Analogue Scale, VAS) and Oswestry Disability Index (ODI) of low back pain and pain around the buttocks were recorded before and 1, 3, 6, and 12 months after the operation, and the modified MacNab criteria were evaluated. curative effect. A total of 45 patients completed surgery and received complete postoperative follow-up.\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eResults\u003c/strong\u003e: The 45 patients in this group all completed the operation successfully. There was no patient who could not tolerate the pain of local anesthesia and was forced to interrupt. The operation time was 65 to 125 minutes, with an average of 94.71±17.67 minutes. The average follow-up time for all patients was 12-18 months. , An average of 13.6±1.9months, the VAS scores for lower back pain and pain around the hips were 6.95±1.02 before surgery, 2.64±0.71 at 1 month after surgery, 1.80±0.54 at 3 months after surgery, and at 6 months after surgery 1.42±0.50, 12 months after surgery, 1.27±0.45; Oswsetry dysfunction index was 72.84±5.95 before surgery, 35.11±5.30 at 1 month after surgery, 25.22±4.85 at 3 months after surgery, and 6 months after surgery It was 16.78±4.63, and it was 10.91±2.36 after 12 months. The VAS score and ODI index of low back pain, lower limb pain at different time points after operation were significantly improved compared with that before operation (P\u0026lt;0.01). The effect of modified MacNab was excellent in 24 cases, good in 13 cases, and fair in 8 cases. The excellent and good rate was 82.22%. Among them, 1 patient developed femoral nerve palsy after endoscopic surgery, and was given a conservative treatment plan for neurotrophic therapy, acupuncture and moxibustion, and functional exercise. The symptoms disappeared 4 weeks after the operation. One patient developed neck and back pain during the operation and was considered as a class. The hypertension of the spinal cord was treated with removal of water pressure and oxygen inhalation, and the symptoms disappeared after 30 minutes. There were no serious surgical complications such as permanent nerve damage and intervertebral space infection in all cases. \u003c/p\u003e\u003cp\u003e\u003cstrong\u003eConclusion\u003c/strong\u003e: Percutaneous spinal endoscopic \"isolation zone\" technology through pedicle-flavum tunnel is a minimally invasive spinal surgery technique for the treatment of discogenic low back pain with safe operation and satisfactory clinical results.\u003c/p\u003e","manuscriptTitle":"Clinical study on the treatment of discogenic low back pain by endoscopic \"isolation zone\" technique through pedicle-flavum tunnel","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2022-06-22 18:43:37","doi":"10.21203/rs.3.rs-1761550/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"26a356bf-b9d9-4e08-970c-ed7d57205035","owner":[],"postedDate":"June 22nd, 2022","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2023-02-15T08:44:20+00:00","versionOfRecord":[],"versionCreatedAt":"2022-06-22 18:43:37","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-1761550","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-1761550","identity":"rs-1761550","version":["v1"]},"buildId":"ApUGefWb6u5IBVtyqm6d5","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}