Intraoperative and Postoperative Ultrasonographic Spinal Cord Evaluation of Cervical Double-Door Laminoplasty.

BACKGROUND: Ultrasonography is a useful tool for the localization, morphology, and characterization of lesions and is increasingly being applied to spinal cord evaluation in cervical spine diseases. However, in conventional cervical laminoplasty, detailed evaluation is difficult because of ultrasound attenuation. Therefore, the purpose of this study was to perform a cervical laminoplasty using a modified surgical technique and evaluate the spinal cord. METHODS: The spinal cord was evaluated intraoperatively and one week postoperatively in 11 patients with cervical compressive myelopathy. Double-door laminoplasty was selected as the surgical method, and the shape and placement of the bone graft between the expanded laminas were devised to reduce ultrasonic attenuation, such that there was a large space in which the dura mater was visible. RESULTS: Intraoperative and postoperative spinal cord decompression, claudication, and pulsation were confirmed in all cases. A more precise diagnosis was possible using ultrasound attenuation using the grafted bone between the laminas as an indicator. CONCLUSION: Intraoperative and postoperative spinal cord decompression status and wave patterns of modified cervical double-door laminoplasty can be evaluated using ultrasonography. Ultrasound-based evaluations of the spinal cord may provide new insights.

Impact of spinal surgery on locomotive syndrome in patients with lumbar spinal stenosis in clinical decision limit stage 3: a retrospective study.

BACKGROUND: Locomotive syndrome (LS) is characterized by reduced mobility. Clinical decision limit (CDL) stage 3 in LS indicates physical frailty. Lumbar spinal canal stenosis (LSS) is one of the causes of LS, for which lumbar surgery is considered to improve the CDL stage. This study aimed to investigate the efficacy of lumbar surgery and independent factors for improving the CDL stage in patients with LSS. METHODS: This retrospective study was conducted at the Department of Orthopaedic Surgery at our University Hospital. A total of 157 patients aged ≥ 65 years with LSS underwent lumbar surgery. The 25-Question Geriatric Locomotive Function scale (GLFS-25) was used to test for LS, and the Timed Up and Go test (TUG) was used to evaluate functional ability. Lower limb pain was evaluated using a visual analog scale. Patients with at least one improvement in the CDL stage following lumbar surgery were included in the improvement group. Differences in lower limb pain intensity between the groups were evaluated using the Wilcoxon rank-sum test. The Spearman's rank correlation coefficient was used to determine correlations between Δ lower limb pain and Δ GLFS-25. Logistic regression analysis was used to identify factors associated with improvement in LS. RESULTS: The proportion of patients with improved CDL stage was 45.1% (improvement/non-improvement: 32/39). Δ Lower limb pain was significantly reduced in the improvement group compared with that in the non-improvement group (51.0 [36.3-71.0] vs 40.0 [4.0-53.5]; p = 0.0107). Δ GLFS-25 was significantly correlated with Δ lower limb pain (r = 0.3774, p = 0.0031). Multiple logistic regression analysis revealed that TUG and age were significantly associated with improvement in LS (odds ratio, 1.22; 95% confidence interval: 1.07-1.47). CONCLUSIONS: Lumbar surgery effectively improved the CDL stage in patients with LSS. In addition, TUG was an independent factor associated with improvement in the CDL.

Preliminary Clinical Experience with a High-Definition Three Dimensional Exoscope for Spinal Surgery.

We retrospectively evaluated spinal surgeries performed using the high-definition three-dimensional exoscopic system, which became available at our institution in August 2020. Eleven patients (4 with cervical disease and 7 with lumbar disease) underwent surgery with the system. There were no surgical complications related to the system, and the results were satisfactory. The small, flexible camera of the exoscope allows the surgeon to view the surgical field from various angles, facilitating both the approach and technique. In addition, it allows the surgeon to operate in an upright position without strain on the head and neck. Although further surgical experience is needed, this system has the potential to improve the visualization of the surgical field in spinal surgery.

Phase angle is related to physical function and quality of life in preoperative patients with lumbar spinal stenosis.

Lumbar spinal stenosis (LSS) can interfere with daily life and quality of life (QOL). Evaluating physical function and QOL and helping patients to improve is the focus of rehabilitation. Phase angle (PhA) assessment is widely used to measure body composition and is considered an indicator of physical function and QOL. This study investigated the relationship between PhA and physical function, physical activity, and QOL in patients with LSS. PhA, handgrip strength, walking speed, Timed Up and Go test (TUG), Life Space Assessment (LSA), Prognostic Nutritional Index (PNI), Japanese Orthopaedic Association Back Pain Evaluation Questionnaire (JOABPEQ), and EQ-5D were assessed and statistically analyzed. The study included 133 patients with LSS. Multiple regression analysis of PhA adjusted for age, sex, and body mass index (Model 1) and for Model 1 + PNI (Model 2) showed significant correlations (P < 0.05) with handgrip strength, walking speed, TUG, and LSA. Regarding QOL, PhA was significantly correlated (P < 0.05) with lumbar function in JOABPEQ. PhA was associated with physical function and QOL in patients with LSS and might be a new clinical indicator in this population.

Risk Factors for Surgical Site Infection in Spinal Surgery and Interventions: A Retrospective Study.

BACKGROUND: Surgical site infection following spinal surgery causes prolonged delay in recovery after surgery, increases cost, and sometimes leads to additional surgical procedures. We investigated risk factors for the occurrence of surgical site infection events in terms of patient-related, surgery-related, and postoperative factors. METHODS: This retrospective study included 1000 patients who underwent spinal surgery in our hospital between April 2016 and March 2019. RESULTS: Patient-related factors were dementia, length of preoperative hospital stay (≥ 14 days), and diagnosis at the time of surgery (traumatic injury or deformity). The one surgery-related factor was multilevel surgery (≥ 9 intervertebral levels), and the one postoperative factor was time to ambulation (≥ 7 days) were statistically significant risk factors for spinal surgical site infection. CONCLUSION: One risk factor identified in this study that is amenable to intervention is time to ambulation. As delayed ambulation is a risk factor for postoperative surgical site infection, how medical staff can intervene in postoperative ambulation to further reduce the incidence of surgical site infection is a topic for future research.

Changes of improvement in upper limb function predict surgical outcome after laminoplasty in 1 year in patients with cervical spondylotic myelopathy: a retrospective study.

BACKGROUND: Cervical spondylotic myelopathy preoperative prognostic factors include age, preoperative severity, and disease duration. However, there are no reports on the relationship between changes in physical function during hospitalization and postoperative course, and in recent years, the length of hospital stay has shortened. We aimed to investigate whether changes in physical function during hospitalization can predict the postoperative outcome. METHODS: We recruited 104 patients who underwent laminoplasty for cervical spondylotic myelopathy by the same surgeon. Physical functions, including Simple Test for Evaluating Hand Function (STEF), grip strength, timed up and go test, 10-m walk, and time to stand on one leg, were assessed at admission and discharge. Patients with the Japanese Orthopaedic Association (JOA) score improvement rate of 50% or more were defined as the improved group. Decision tree analysis was investigated factor for identifying improvement in the JOA score. According to this analysis, we divided into two groups using age. Then, we conducted a logistic regression analysis to identify factors that improve the JOA score. RESULTS: The improved and non-improved groups had 31 and 73 patients, respectively. The improved group was younger (p = 0.003) and had better improved Δgrip strength (p = 0.001) and ΔSTEF (p < .0007). Age was significantly positively correlated with disease duration (r = 0.4881, p = < .001). Disease duration exhibited a significant negative correlation with the JOA score improvement rate (r = - 0.2127, p = 0.031). Based on the decision tree analysis results, age was the first branching variable, with 15% of patients ≥ 67 years showing JOA score improvement. This was followed by ΔSTEF as the second branching factor. ΔSTEF was selected as the factor associated with JOA improvement in patients ≥ 67 years (odds ratio (OR) 0.95, 95% confidence interval (CI) 0.90-0.99, p = .047); in patients < 67 years, Δgrip strength was identified (OR 0.53, CI 0.33‒0.85, p = .0086). CONCLUSIONS: In the improved group, upper limb function improved more than lower limb function from the early postoperative period. Upper limb function changes during hospitalization were associated with outcomes one year postoperatively. Improvement factors in upper extremity function differed by age, with changes in grip strength in patients < 67 years and STEF in patients ≥ 67 years, reflecting the outcome at one year postoperatively.

Intradural extramedullary tumor location in the axial view affects the alert timing of intraoperative neurophysiologic monitoring.

OBJECTIVE: Intraoperative neurophysiologic monitoring (IONM) reportedly helps prevent postoperative neurological complications following high-risk spinal cord surgeries. There are negative and positive reports about using IONM for intradural extramedullary (IDEM) tumors. We investigated factors affecting alerts of IONM in IDEM tumor surgery. METHODS: We analyzed 39 patients with IDEM tumors who underwent surgery using IONM at our hospital between January 2014 and March 2021. Neurological symptoms were evaluated pre- and postoperatively using the manual muscle test (MMT). All patients were evaluated to ascertain the tumor level and location in the axial view, the operative time, intraoperative bleeding volume, and histological type. Additionally, the intraoperative procedure associated with significant IONM changes in transcranial electrical stimulation muscle-evoked potential was investigated. RESULTS: There were 11 false-positive and 16 true-negative cases. There was one true-positive case and one false-negative case; the monitoring accuracy achieved a sensitivity of 50%, a specificity of 59%, a positive predictive value of 8%, and a negative predictive value of 94%. In the 22 alert cases, if the tumor was located anterolateral in the axial view, alerts were triggered with a significant difference (p = 0.02) during tumor resection. Alerts were generated for fifteen patients during tumor resection; nine (60%) showed waveform improvement by intervention and were classified as rescue cases. CONCLUSION: Alert is probably triggered during tumor resection for anterolaterally located tumors. Alerts during tumor resection procedures were more likely to be rescued than other procedures in IDEM tumor surgery.

Improved intervertebral bone union in ALIF rat model with porous hydroxyapatite/collagen combined with platelet-rich plasma.

BACKGROUND CONTEXT: Platelet-rich plasma (PRP) can accelerate bone union in spinal fusion surgery with an autogenous bone graft. However, it is unclear whether bone union can be obtained by using artificial bone and PRP together in spinal interbody fusion surgery. PURPOSE: This study aimed to determine whether interbody fusion can be achieved by transplanting porous hydroxyapatite/collagen(HAp/Col) which is an artificial bone material frequently used in spinal fusion surgery, together with PRP in the intervertebral disc space in rats. STUDY DESIGN AND SETTING: A controlled laboratory study. METHODS: A total of fourty 10-week old Sprague-Dawley rats were used in this study and assigned to three groups as follow: disc curettage only (control group, n=10), disc curettage + HAp/Col transplant (H group, n=10), and disc curettage + HAp/Col + PRP transplant (H+P group, n=10). The other 10 rats were sacrificed as blood donors for acquisition of PRP. Microcomputed tomography (µCT) examinations were performed to evaluate bone union, bone volume (BV), and bone mineral density (BMD) at 4, 8, and 12 weeks following surgery. Twelve weeks postoperatively, each group of three of L4-L5 spines was harvested to perform histological examination (hematoxylin & eosin stain) and the others were subjected to biomechanical testing (compression properties). RESULTS: The platelet count in PRP was approximately 4.1 times greater than that in whole blood (260.6±26.2 × 104 mg/dL and 64.3±2.9 × 104 mg/dL in PRP and whole blood, respectively). All the L4-L5 lumbar discs were fused in the H+P group, whereas only one case was fused in the H group and none in the control group at 12 weeks after surgery. BV was significantly higher in the H+P group than in the H group or control groups (both p<.01), although BMD was not significantly different among the three groups. Upon histological analysis, mature bone formation was observed at the transplanted space in all cases in the H+P group, whereas fibrous tissue was observed at the location in the H and control groups. Regarding biomechanical properties, the ultimate load to failure was significantly higher in the H+P group than in the H group or control group (p=.021 and .013, respectively), although stiffness was not significantly different between the three groups. CONCLUSION: The combination of porous HAp/Col and PRP at an appropriate concentration can promote bone union in the intervertebral disc space without using an autologous bone graft in the rat model. Bone tissue formation was histologically confirmed, and it was mechanically strong. CLINICAL SIGNIFICANCE: This preclinical study showed that porous HAp/Col, when combined with PRP at an appropriate concentration, can induce bone union without autologous bone grafts. The results may eliminate the need for autologous bone collection for spinal fusion surgery in the future.

Computed Tomographic Epidurography in Patients with Low Back Pain and Leg Pain: A Single-Center Observational Study.

This study was conducted to analyze the findings and benefits of computed tomography (CT) epidurography in patients with low back and leg pain and compare these findings with those of magnetic resonance imaging (MRI) images. In total, 495 intervertebral discs from 99 patients with low back and leg pain who underwent percutaneous epidural adhesiolysis (epidural neuroplasty or percutaneous adhesiolysis) were examined. The axial views of CT epidurography were classified into six types to examine each intervertebral disc: round type, ellipse type, spike type, Benz mark, incomplete block, complete block, and non-contrast. MRI images were graded from A to D using the Schizas classification. Notably, 176 images were round-type and ellipse-type axial views, and 138 were spike-type and Benz-mark views; Schizas classification Grades A and B were observed in 272 and 47 MRI images, respectively. The incomplete block and complete block axial images did not significantly differ in CT epidurography and Schizas classification Grades C and D. The images showing Benz marks existed only at the L4/5 and L5/S intervertebral levels and only in 14.7% of patients. The ratio of normal shadows differed between MRI images and CT epidurography. Therefore, CT epidurography may enable a detailed evaluation of the epidural space.

Efficacy of Minimally Invasive Trans-Sacral Canal Plasty between Patients with and without Failed Back Surgery Syndrome.

Background and Objectives: Clinicians are required to manage a growing number of elderly patients with several medical comorbidities, and invasive surgical treatments are sometimes not advisable for these patients. The aim of this study was to evaluate the efficacy of minimally invasive intraspinal canal treatment, trans-sacral canal plasty (TSCP), for patients with and without failed back surgery syndrome (FBSS). Materials and Methods: A multicenter analysis was conducted. TSCP was performed in patients with chronic low back pain and leg pain due to lumbar spinal disorders. An adhesiolysis by TSCP was carried out, then a mixture of steroid and local anesthesia was injected. Visual Analog Scales (VAS) for low back pain and leg pain, and complications were evaluated. Results: A total of 271 patients with a minimum 6-month follow-up were enrolled. There were 80 patients who had a history of previous lumbar spinal surgery (F group), and 191 patients without previous lumbar spinal surgery (N group). There were no significant differences in sex and age between the two groups. VAS scores for low back pain (N group/F group) preoperatively, immediately postoperatively, and 1 month, 3 months and 6 months postoperatively, were 51/52 mm, 24/26 mm, 33/34 mm, 30/36 mm, and 30/36 mm, respectively. VAS scores for leg pain were 69/67 mm, 28/27 mm, 39/41 mm, 36/43 mm, and 32/40 mm, respectively. Both VAS scores for low back pain and leg pain were significantly decreased from baseline to final follow-up in both groups (p < 0.01). However, VAS scores for leg pain at 3 months and 6 months postoperatively were significantly higher in F group (p < 0.05). There were three catheter breakages (2/3 in F group), and one dural tear in F group. Conclusions: TSCP significantly reduced both VAS scores for low back and leg pain in patients with and without FBSS. However, co-existence of intractable epidural adhesion might be associated with less improvement in FBSS.

The impact of sarcopenia on low back pain and quality of life in patients with osteoporosis.

PURPOSE: Osteoporosis combined with sarcopenia contributes to a high risk of falling, fracture, and even mortality. However, sarcopenia's impact on low back pain and quality of life (QOL) in patients with osteoporosis is still unknown. The purpose of this study is to investigate low back pain and QOL in osteoporosis patients with sarcopenia. METHODS: We assessed 100 ambulatory patients who came to our hospital for osteoporosis treatment. Low back pain was evaluated using the Visual Analogue Scale (VAS) with 100 being an extreme amount of pain and 0 no pain. The Japanese Orthopaedic Association Back Pain Evaluation Questionnaire (JOABPEQ) score was used to assess QOL after adjustment for age, history of vertebral fracture, and adult spinal deformity. Differences in low back pain intensity assessed by VAS between groups were evaluated by the Willcoxon rank-sum test. Covariance analysis was used to assess QOL. All data are expressed as either median, interquartile range, or average, standard error. RESULTS: Patients were classified into the sarcopenia group (n = 32) and the non-sarcopenia group (n = 68). Low back pain intensity assessed by VAS was significantly higher in the sarcopenia group than in the non-sarcopenia group (33.0 [0-46.6] vs. 8.5 [0-40.0]; p < 0.05). The subscales of the JOABPEQ for low back pain were significantly lower in the sarcopenia group than in the non-sarcopenia group (65.0 ± 4.63 vs. 84.0 ± 3.1; p < 0.05). CONCLUSION: In this cross-sectional study, sarcopenia affected low back pain and QOL in ambulatory patients with osteoporosis. Sarcopenia may exacerbate low back pain and QOL.

Pyogenic Spondylitis: Clinical Features, Diagnosis and Treatment.

Although pyogenic spondylitis is an infrequent infection, its incidence is increasing because of the growing number of elderly people and immunocompromised patients. Diagnosis is often difficult and appropriate imaging, blood cultures and/or biopsy are essential in making an early diagnosis. Most of the cases can be treated non-operatively. Surgical treatment is indicated in patients with spinal cord or cauda equine compression with progressive neurological deficits and/or patients who have failed conservative treatment. Early and accurate diagnosis of pyogenic spondylitis is important for timely and effective management, in order to reduce the occurrence of spinal deformity and dysfunction.

Up-regulation in receptor for advanced glycation end-products in inflammatory circumstances in bovine coccygeal intervertebral disc specimens in vitro.

STUDY DESIGN: This study investigated whether or not the receptor for advanced glycation end-products (RAGE) was up-regulated in inflammatory circumstances and consequently associated with aggrecan content in nucleus pulposus in vitro. OBJECTIVE: To investigate the activation of AGEs-RAGE complex by the irritation of IL-1beta in bovine intervertebral disc (IVD). SUMMARY OF BACKGROUND DATA: Although we have demonstrated that the accumulation of AGEs contributed to disc degeneration in human, it may be that acceleration in the AGEs-RAGE complex might be more important, mediated by expression levels of RAGE that increase in inflammatory mediators including IL-1beta in some tissues. Therefore, we investigated, in this study, the correlation if any between IL-1beta and AGEs-RAGE complex in bovine IVD. METHODS: Samples of bovine coccygeal IVDs were harvested (n = 6). The presence of AGEs and RAGE were identified by immunohistochemistry. Real-time polymerase chain reaction (PCR) was used to quantify the messenger RNA levels of aggrecan after 6 days' stimulation of AGEs. Real-time PCR and immunofluorescein cytochemistry were performed to analyze the expression of RAGE after 2 days' stimulation of IL-1beta. The aggrecan expressions were evaluated by real-time PCR after 2 days' stimulation of combination of AGEs and/or IL-1beta. RESULTS: Immunohistochemical analysis revealed that AGEs and RAGE were localized within the bovine IVDs. AGEs significantly decreased the aggrecan expression in bovine IVD as in human IVD. The RAGE expression was significantly increased by 2 days' stimulation of IL-1beta. The aggrecan expression was decreased by stimulated AGEs and IL-1beta together, although not decreased by stimulated AGEs or IL-1beta separately. CONCLUSION: This is the first report to show the correlation between IL-1beta and AGEs-RAGE complex in IVD. Our results suggested that the increased RAGE expression in inflammatory circumstances and interaction with AGEs are risk factors in decreasing of aggrecan content in nucleus pulposus.

Effect of a nonprotein bioactive agent on the reduction of cyclooxygenase-2 and tumor necrosis factor-alpha in human intervertebral disc cells in vitro.

OBJECT: Neurotropin is a nonprotein extract from the inflamed skin of rabbits inoculated with vaccinia virus. In the present study the authors sought to clarify the focal antiinflammatory effects of Neurotropin in intervertebral disc cells, and these effects were compared with those induced by the selective cyclooxygenase (COX)-2 inhibitor 6-methoxy-2-naphthylacetic acid (nabumetone). METHODS: Six human intervertebral disc specimens were harvested during spinal surgery for lumbar disc herniation. Cells were stimulated with 500 pg/ml of interleukin (IL)-1beta in the presence of various concentrations of Neurotropin (0, 10(-5), 10(-4), and 10(-3) Neurotropin Units/ml) or 50 microg/ml of nabumetone for 3 hours. The mRNA was extracted for polymerase chain reaction (PCR), and real-time PCR was used to quantify the mRNA levels of COX- 2, tumor necrosis factor (TNF)-alpha, and phospholipase A2. Cyclooxygenase-2, TNFalpha, and prostaglandin E2 (PGE2) protein concentrations were each determined by enzyme-linked immunosorbent assay. RESULTS: Neurotropin was found to significantly suppress the expression of COX-2 and TNFalpha at mRNA levels as well as the concentration of COX-2 at protein levels in a dose-dependent manner. Nabumetone was found to significantly increase COX-2 at mRNA levels but directly suppress the concentration of PGE2 in culture medium. CONCLUSIONS: Results in this study suggest that Neurotropin has an analgesic effect through the suppression of COX-2 and TNFalpha in a focal area, and nabumetone shows this same effect through the suppression of PGE2 production. Thus, Neurotropin could decrease pain by blocking the central pain pathway or increasing focal antiinflammatory effects.

Immunohistochemical demonstration of advanced glycation end products and the effects of advanced glycation end products in ossified ligament tissues in vitro.

STUDY DESIGN: This study correlates advanced glycation end products with ossified ligament tissues of the cervical spine in vitro. OBJECTIVE: To investigate the effect of advanced glycation end products on ossification of the spinal ligaments in vitro. SUMMARY OF BACKGROUND DATA: We have hypothesized that an accumulation of advanced glycation end products in the spinal ligament might result in some observable change in specific growth factors responsible for ossification in the spinal ligaments. METHODS: Samples of the posterior longitudinal and yellow ligaments were harvested from patients (n = 5) with ossification of the posterior longitudinal ligament, and analyzed for the presence of advanced glycation end products and their receptor advanced glycation end product receptor by immunohistochemistry. Real-time polymerase chain reaction (PCR) was used to quantify the messenger ribonucleic acid (mRNA) levels of bone morphogenetic protein (BMP)-2, BMP-7, alkaline phosphatase, an osteoblast-specific transcription factor 1 (Cbfa1), and osteocalcin from yellow ligament cells treated with advanced glycation end products. RESULTS: Immunohistochemical analysis revealed that advanced glycation end products and advanced glycation end product receptor were localized to within the posterior longitudinal and yellow ligaments. Advanced glycation end products were found to increase significantly the expression of BMP-2, BMP-7, Cbfa1, and osteocalcin at the mRNA levels after treatment with advanced glycation end products (1 microg/mL). CONCLUSIONS: This is the first report to investigate the correlation, if any, between the ossified spinal ligament and advanced glycation end products. These results suggested that accumulation in advanced glycation end products and their interaction with advanced glycation end product receptor were 1 of the important risk factors in the process of ossification in the spinal ligaments.

Advanced glycation end-products downregulating intervertebral disc cell production of proteoglycans in vitro.

OBJECT: The authors sought to clarify the role, if any, of advanced glycation end-products (AGEs) in disc degeneration. METHODS: Intervertebral discs were analyzed for the presence of AGEs and of their receptor (RAGE) by immunohistochemical analysis. Reverse transcriptase polymerase chain reaction (RT-PCR) was performed to detect any RAGE gene expression, and real-time PCR was used to quantify messenger RNA (mRNA) levels of aggrecan and collagen types I and II in nucleus pulposus cells treated with AGEs. Aggrecan protein concentration was determined by enzyme-linked immunosorbent assay. Immunohistochemical analysis revealed that AGEs and RAGE were localized in the nucleus pulposus of the intervertebral disc. Advanced glycation end-products were found to significantly suppress the expression of aggrecan at both mRNA and protein levels in a dose- and time-dependent manner. The levels of collagen types I and II remained unchanged after treatments with AGEs. CONCLUSIONS: These results suggest that the accumulation of AGEs and their interaction with their receptor in the nucleus pulposus might result in the downregulation of aggrecan production responsible for disc degeneration.

Positive feedback loop of interleukin-1beta upregulating production of inflammatory mediators in human intervertebral disc cells in vitro.

OBJECT: Interleukin-1beta (IL-1beta) induces neurological symptoms in intervertebral disc herniation (IDH). Recently, the existence of a positive feedback loop of IL-1beta, which encourages an inflammatory reaction or degeneration in the cells of tendon, has been reported. The authors hypothesized that there is a positive feedback loop of IL-1beta in the cells of IDH. METHODS: Eight human intervertebral disc specimens were harvested during spinal surgery for lumbar disc herniation. The cells were stimulated in serum-free medium with or without exogenous IL-1beta. The messenger RNA (mRNA) was extracted for reverse-transcription polymerase chain reaction (PCR) and real-time PCR to quantify the mRNA of endogenous IL-1beta, IL-6, cyclooxygenase-2 (COX-2), and matrix metalloproteinases (MMPs). The cells were then stimulated in serum-free medium with or without exogenous IL-1beta, and then exogenous IL-1beta was removed. After 2, 4, and 6 days, the medium was collected, and enzyme-linked immunosorbent assay was used to measure the protein concentration of endogenous IL-1beta. The mRNA expressions of endogenous IL-1beta, IL-6, COX-2, and MMPs were increased significantly depending on the concentration of exogenous IL-1beta. The protein concentration of endogenous IL-1beta was increased over time. CONCLUSIONS: There was a positive feedback loop of IL-1beta in the cells of IDH. Furthermore, the productions of IL-6, COX-2, MMP-1, and MMP-3 were upregulated as a result of the increasing concentration of IL-1beta in a positive feedback loop of IL-1beta. The authors concluded that this positive feedback loop of IL-1beta upregulated the production of mediators and thus can cause cessation of symptoms in IDH.