Protectin D1 ameliorates non-compressive lumbar disc herniation through SIRT1-mediated CGRP signaling.

Background. Neuro-inflammatory response promotes the initiation and sustenance of lumbar disc herniation (LDH). Protectin D1 (PD1), as a new type of specialized pro-resolving mediator (SPM), can improve the prognosis of various inflammatory diseases. Recent studies have shown that over representation of calcitonin gene-related peptides (CGRP) may activate nociceptive signaling following nerve injury. Silent information regulator 1 (SIRT1) is ubiquitously expressed in the dorsal horn of the spinal cord and plays a role in the pathogenesis of LDH. In this study, we investigated the analgesic effects of PD1 and elucidated the impact of neurogenic inflammation in the pathogenesis of neuropathic pain induced by non-compressive lumbar disc herniation (NCLDH) in a rat model. Methods. NCLDH models were established by applying protruding autologous nucleus pulposus to the L5 Dorsal root ganglion (DRG). PD1, SIRT1 antagonist or agonist, CGRP or antagonist were administered as daily intrathecal injections for three consecutive days postoperatively. Behavioral tests were conducted to assess mechanical and thermal hyperalgesia. The ipsilateral lumbar (L4-6) segment of the spinal dorsal horn was isolated for further analysis. Alterations in the release of SIRT1 and CGRP were explored using western blot and immunofluorescence. Results. Application of protruded nucleus (NP) materials to the DRG induced mechanical and thermal allodynia symptoms, and deregulated the expression of pro-inflammatory and anti-inflammatory cytokines in rats. Intrathecal delivery of PD1 significantly reversed the NCLDH-induced imbalance in neuro-inflammatory response and alleviated the symptoms of mechanical and thermal hyperalgesia. In addition, NP application to the DGRs resulted the spinal upregulation of CGRP and SIRT1 expression, which was almost restored by intrathecal injection of PD1 in a dose-dependent manner. SIRT1 antagonist or agonist and CGRP or antagonist treatment further confirmed the result. Conclusion. Our findings indicate PD1 has a potent analgesic effect, and can modulate neuro-inflammation by regulating SIRT1-mediated CGRP signaling in NCLDH.

Surgery versus Conservative Care for Persistent Sciatica Lasting 4 to 12 Months.

BACKGROUND: The treatment of chronic sciatica caused by herniation of a lumbar disk has not been well studied in comparison with acute disk herniation. Data are needed on whether diskectomy or a conservative approach is better for sciatica that has persisted for several months. METHODS: In a single-center trial, we randomly assigned patients with sciatica that had lasted for 4 to 12 months and lumbar disk herniation at the L4-L5 or L5-S1 level in a 1:1 ratio to undergo microdiskectomy or to receive 6 months of standardized nonoperative care followed by surgery if needed. Surgery was performed by spine surgeons who used conventional microdiskectomy techniques. The primary outcome was the intensity of leg pain on a visual analogue scale (ranging from 0 to 10, with higher scores indicating more severe pain) at 6 months after enrollment. Secondary outcomes were the score on the Oswestry Disability Index, back and leg pain, and quality-of-life scores at 6 weeks, 3 months, 6 months, and 1 year. RESULTS: From 2010 through 2016, a total of 790 patients were screened; of those patients, 128 were enrolled, with 64 in each group. Among the patients assigned to undergo surgery, the median time from randomization to surgery was 3.1 weeks; of the 64 patients in the nonsurgical group, 22 (34%) crossed over to undergo surgery at a median of 11 months after enrollment. At baseline, the mean score for leg-pain intensity was 7.7 in the surgical group and 8.0 in the nonsurgical group. The primary outcome of the leg-pain intensity score at 6 months was 2.8 in the surgical group and 5.2 in the nonsurgical group (adjusted mean difference, 2.4; 95% confidence interval, 1.4 to 3.4; P<0.001). Secondary outcomes including the score on the Owestry Disability Index and pain at 12 months were in the same direction as the primary outcome. Nine patients had adverse events associated with surgery, and one patient underwent repeat surgery for recurrent disk herniation. CONCLUSIONS: In this single-center trial involving patients with sciatica lasting more than 4 months and caused by lumbar disk herniation, microdiskectomy was superior to nonsurgical care with respect to pain intensity at 6 months of follow-up. (Funded by Physicians' Services Incorporated Foundation; ClinicalTrials.gov number, NCT01335646.).

Caudal epidural steroid injection versus transforaminal ESI for unilateral S1 radiculopathy: a prospective, randomized trial.

OBJECTIVE: Epidural steroid injections are frequently performed to manage radicular symptoms. Most research investigating the effectiveness of different routes of epidural injections were conducted with non-homogeneous groups. In this study our aim was to investigate the efficacy of caudal versus transforaminal approaches in patients with unilateral S1 radiculopathy secondary to a paracentral L5-S1 disc herniation. STUDY DESIGN: Prospective, randomized clinical trial. SETTING: A university hospital pain management center. METHODS: The study was conducted between January 2022 and February 2023. Patients with unilateral S1 radiculopathy were randomly divided into two groups: the caudal epidural steroid injection (CESI) and the transforaminal epidural steroid injection (TFESI) group. Severity of pain and disability were assessed with Numeric Rating Scale (NRS-11) and Oswestry Disability Index (ODI) at baseline, 3 weeks, and 3 months after treatment. Fifty percent or more improvement in NRS-11 was defined as treatment success. Fluoroscopy time and doses of exposed radiation were also recorded. RESULTS: A total of 60 patients were included in the final analysis (n = 30 for each group). Significant improvement in pain and disability scores was observed at 3rd week and 3rd month compared to baseline (P < .001). Treatment success rate at 3rd month was 77% for the CESI group and 73% for the TFESI group without any significant difference between the groups (P = .766). CONCLUSIONS: CESI is equally effective as TFESI in the management of S1 radiculopathy due to a paracentral L5-S1 disc herniation. Both approaches can reduce pain and disability, while CESI requires shorter fluoroscopy time and less radiation exposure.

Development process and clinical application of collagenase chemonucleolysis in the treatment of lumbar disc herniation: a narrative review in China.

Lumbar disc herniation (LDH) is one of the most common causes of lumbocrural pain. In the past 20 years, the incidence of LDH has increased dramatically. There are many treatments for LDH, including conservative treatment (such as acupuncture and physiotherapy), minimally invasive interventional treatment (such as collagenase chemonucleolysis and radiofrequency ablation) and surgical treatment. The main purpose of this paper is to review the development process and application status of collagenase chemonucleolysis in the treatment of LDH at home and abroad and provide a reference for clinical treatment.

"Platelet-Rich Plasma" epidural injection an emerging strategy in lumbar disc herniation: a Randomized Controlled Trial.

BACKGROUND: Lumbar herniated disc (HNP) is mainly treated by conservative management. Epidural steroid injection (ESI) has been an option to treat failed cases prior to surgery. Triamcinolone has been widely used due to its efficacy in bringing about pain reduction for up to three months. However, several reports have shown some severe adverse events. Platelet-rich plasma (PRP) is made from blood through centrifugation. Several studies supported the potential short to long-term effects, and safety of PRP injection in treating HNP. The study objective was to evaluate the efficacy of PRP in treatment of single-level lumbar HNP in comparison to triamcinolone. METHODS: Thirty patients were treated by transforaminal epidural injections. PRP was obtained from 24 ml venous blood through standardized double-spin protocol. Participants included fifteen patients each being in triamcinolone and PRP groups. The same postoperative protocols and medications were applied. The visual analogue scale of leg (LegVAS), collected at baseline, 2, 6, 12, and 24 weeks, was the primary outcome. The BackVAS, Oswestry Disability Index (ODI), adverse event, and treatment failure were the secondary endpoints. RESULTS: Platelet ratio of PRP in fifteen patients was 2.86 ± 0.85. Patients treated by PRP injections showed statistically and clinically significant reduction in LegVAS at 6, 12, and 24 weeks, and in ODI at 24 weeks. It demonstrated comparable results on other aspects. No adverse event occurred in either group. CONCLUSION: Noncommercial epidural double-spin PRP yielded superior results to triamcinolone. Due to its efficacy and safety, the procedure is recommended in treating single level lumbar HNP. TRIAL REGISTRATION: NCT, NCT05234840. Registered 1 January 2019, https://clinicaltrials.gov/ct2/show/record/NCT05234840 .

Effect of sacralization on the success of lumbar transforaminal epidural steroid injection treatment: prospective clinical trial.

OBJECTIVE: The aim of this study was to invastigate the effect of the sacralization on the results of transforaminal epidural steroid injection for radicular low back pain. MATERIALS AND METHODS: The study included 64 patients diagnosed with radicular low back pain due to unilateral and single-level lumbar disk herniation. Patients were divided into 2 groups: patients with sacralization (Group S) and patients without lumbosacral transitional vertebrae (Group A). Injection was applied to the relevant level. Patients were evaluated with Numeric Rating Scale and Modified Oswestry Disability Index before, at week 3 and month 3 after the procedure. Sacralization presence was determined by MRI. Sacralization was categorized by anteroposterior lumbar radiography using Castellvi classification. Treatment success was considered as ≥ 50% reduction in NRS scores. RESULTS: Numeric Rating Scale and Modified Oswestry Disability Index scores decreased in both groups on both week 3 and month 3 (p < 0.05). Pain scores of Group S (median value 5 (3-6)) were significantly higher than Group A ((median value 3 (0-5)) in the third month follow-up (p = 0.026), but no significant difference was observed at other time points. There was no significant difference in Modified Oswestry Disability Index scores between the groups at all follow-ups (p > 0.05). Treatment success in the third month was 44.8% in Group S and 65.6% in Group A. CONCLUSION: Transforaminal epidural steroid injection is an effective and safe method for radicular low back pain. Sacralization presence should be evaluated before treatment considering that it may be a risk factor reducing treatment success.

Cytokine Imbalance as a Biomarker of Intervertebral Disk Degeneration.

The intervertebral disk degeneration (IDD) and its associated conditions are an important problem in modern medicine. The onset of IDD may be in childhood and adolescence in patients with a genetic predisposition. IDD progresses with age, leading to spondylosis, spondylarthrosis, intervertebral disk herniation, and spinal stenosis. The purpose of this review is an attempt to summarize the data characterizing the patterns of production of pro-inflammatory and anti-inflammatory cytokines in IDD and to appreciate the prognostic value of cytokine imbalance as its biomarker. This narrative review demonstrates that the problem of evaluating the contribution of pro-inflammatory and anti-inflammatory cytokines to the maintenance or alteration of cytokine balance may be a new key to unlocking the mystery of IDD development and new therapeutic strategies for the treatment of IDD in the setting of acute and chronic inflammation. The presented data support the hypothesis that cytokine imbalance is one of the most important biomarkers of IDD.

Molecular Basic of Pharmacotherapy of Cytokine Imbalance as a Component of Intervertebral Disc Degeneration Treatment.

Intervertebral disc degeneration (IDD) and associated conditions are an important problem in modern medicine. The onset of IDD may be in childhood and adolescence in patients with a genetic predisposition. With age, IDD progresses, leading to spondylosis, spondylarthrosis, herniated disc, spinal canal stenosis. One of the leading mechanisms in the development of IDD and chronic back pain is an imbalance between pro-inflammatory and anti-inflammatory cytokines. However, classical therapeutic strategies for correcting cytokine imbalance in IDD do not give the expected response in more than half of the cases. The purpose of this review is to update knowledge about new and promising therapeutic strategies based on the correction of the molecular mechanisms of cytokine imbalance in patients with IDD. This review demonstrates that knowledge of the molecular mechanisms of the imbalance between pro-inflammatory and anti-inflammatory cytokines may be a new key to finding more effective drugs for the treatment of IDD in the setting of acute and chronic inflammation.

The inhibitory effect of neurotropin on inflammation in rats with lumbar disc herniation based on the c-JNK/CXCL1 signaling pathway.

This study aimed to investigate the inhibitory effect and mechanism of neurotropin on inflammation in rats with lumbar disc herniation. For this purpose, forty-eight rats were randomly divided into sham group, autologous nucleus pulposus transplantation model group (NP group), neurotropin treatment group (NP+NT group), and solvent [normal saline (NS)] control group (NP+NS group). After 7 days of intervention, the mechanical paw withdrawal threshold (PWT) and thermal paw withdrawal latency (PWL) of the rats were measured, and the expression levels of Iba-1, c-JNK and CXCL1 in spinal cord tissues were measured by Western blot. The levels of tissue-associated inflammatory and anti-inflammatory factors in the spinal cord were detected by ELISA. Results showed that Neurotropin significantly alleviated mechanical and thermal hyperalgesia induced by NP transplantation and reduced levels of Iba-1, c-JNK, and CXCL1 proteins in the spinal cord tissue. In addition, neurotoxins also lowered concentrations of the inflammatory factors IL-1ß, IL-6 and TNF-α. It was concluded that Neurotropin has an inhibitory effect on lumbar disc herniation-induced spinal cord inflammation through inhibition of the c-JNK/CXCL signaling pathway.

Comparative effect of transforaminal injection of Magnesium sulphate versus Ozone on oxidative stress biomarkers in lumbar disc related radicular pain.

BACKGROUND: We aimed to investigate the effect of transforaminal injection of Magnesium sulphate versus Ozone on pain intensity, functional disability and the oxidative stress biomarkers; superoxide dismutase (SOD) and Glutathione (GSH) in patients with lumbar disc prolapse. METHODS: This randomized controlled trial was conducted on 135 patients having symptomatic lumbar disc prolapse, received either transforaminal injection of Magnesium sulphate with steroids, Ozone with steroids, or steroids alone. Assessment of pain severity and functional disability were done before intervention, 2 weeks, 1, 3, and 6 months after intervention. Serum SOD and GSH were measured for all included patients before and 2 weeks after intervention. RESULTS: There was a statistically significant improvement in pain intensity and functional disability 2 weeks after intervention in the three groups, but at 1-month and 3-months after intervention, the significant improvement was in Mg sulphate and Ozone groups only. At 6-months follow up, Mg sulphate group only showed a significant improvement. There was a statistically significant increase in SOD and GSH serum levels, 2-weeks after intervention in both Magnesium sulphate (P-value = 0.002, 0.005 respectively) and ozone groups (P-value < 0.001, < 0.001), but there was no statistically significant change in SOD and GSH serum levels in control group. CONCLUSION: Transforaminal injection of Mg sulphate in patients with lumbar disc prolapse causes significant long-term improvement (up to 6 months) in pain intensity and functional disability. The serum levels of SOD and GSH were significantly increased at 2 weeks following both transforaminal injection of Mg sulphate and ozone.

Effectiveness of epidural steroid injection in patients with lumbar herniated intervertebral disc under a "wait-and-see" policy.

BACKGROUND: There are no consensus and guidelines on the optimal interval of repeat epidural steroid injections (ESI) for patients with lumbar herniated intervertebral disc (HIVD) who respond to initial ESI. PURPOSE: To evaluate the effectiveness of ESI in patients with HIVD under a "wait-and-see" policy, i.e. as-needed injections not on a predetermined schedule. MATERIAL AND METHODS: A total of 592 patients with lumbar HIVD received spine injections between January and December 2017. After excluding patients with excellent (no pain) or poor (>70% residual symptoms) response in the two- or three-week pain assessment, the data of 141 responders were analyzed (60 men, 73 women; age = 50.55±17.25 years). We divided patients into wait-and-see (n=124) and early repeat-ESI (n=17) groups, who received repeat ESIs within three weeks. Evaluations of characteristics and outcomes were performed with the chi-square test or independent Student's t-test. RESULTS: Six patients (4.8%) in the wait-and-see group and 1 (5.9%) in the early repeat-ESI group underwent operation within one year (P=0.85). A mean of 1.52±0.82 ESIs was performed in the wait-and-see and a mean of 2.29±0.47 ESIs in the early repeat-ESI group over one year (P<0.001). The time interval between the first and second ESIs was longer in the wait-and-see group than in the early repeat-ESI group (97.15 vs. 15.47 days, P<0.001). Seventy-eight patients (62.9%) in the wait-and-see group could control their pain with a single ESI. CONCLUSION: A "wait-and-see" policy could be an effective pain management option for patients with lumbar HIVD who respond to initial ESI.

Effects of Local Anesthetics With or Without Steroids in High-Volume Transforaminal Epidural Blocks for Lumbar Disc Herniation: A Randomized, Double-Blind, Controlled Trial.

BACKGROUND: Lumbar transforaminal epidural block (TFEB) is an effective treatment modality for radicular pain due to lumbar disc herniation (LDH). The addition of steroids is more effective than local anesthetic alone in TFEBs for patients with LDH. Moreover, the efficacy of TFEBs has been reported to be positively correlated with the volume of injectate. We hypothesized that high-volume TFEBs without steroids effectively alleviate axial back and radicular pain associated with LDH. This study compared the efficacy of high-volume TFEBs with vs. without steroids for the management of the axial and radicular pain caused by LDH. METHODS: A total of 54 patients were randomly assigned to either group L or group D. Patients in group L received 8-mL injections of 0.33% lidocaine only. Patients in group D received 8-mL injections of 0.33% lidocaine with 5 mg of dexamethasone. The primary outcomes were pain intensity at baseline and 4 weeks after the procedure. The secondary outcomes included the change of functional disability between baseline and 4 weeks after the procedure, pain scores during injection, and adverse effects. RESULTS: Both groups showed a significant reduction in axial and radicular pain and improvement in the functional status at the outpatient visit 4 weeks after TFEB. However, there were no significant differences between the groups in terms of changes in back pain (10.00 [20.00] vs. 10.00 [22.50]; P = 0.896) or radicular pain (5.00 [20.00] vs. 10.00 [12.50]; P = 0.871). CONCLUSION: High-volume TFEBs with and without steroid administration yielded similar significant pain reductions and functional improvements among LDH patients 4 weeks after the procedure.

Clinical outcomes following intradiscal injections of higher-concentration platelet-rich plasma in patients with chronic lumbar discogenic pain.

PURPOSE: This study aimed to assess clinical outcomes following intradiscal injections of higher-concentration (> 10 ×) platelet-rich plasma (PRP) in patients with chronic lumbar discogenic pain and to compare outcomes with a historical cohort. METHODS: This retrospective study included 37 patients who received intradiscal injections of higher-concentration (> 10 ×) PRP and had post-procedure outcomes data (visual numerical scale pain score, Functional Rating Index [FRI], and NASS Patient Satisfaction Index). Outcomes were compared to a historical cohort of 29 patients who received intradiscal injections of < 5X PRP. RESULTS: Pain and FRI scores significantly improved by 3.4 ± 2.5 and 46.4 ± 27.6, respectively, at 18.3 ± 13.3 months following intradiscal injections of > 10 × PRP (p < 0.001). These improvements were greater than those reported by the historical cohort (1.7 ± 1.6 and 33.7 ± 12.3; p = 0.004 and 0.016, respectively). Additionally, the satisfaction rate was higher in patients receiving > 10 × PRP compared to those receiving < 5 × PRP (81% vs. 55%; p = 0.032). CONCLUSIONS: Findings from this study suggest that clinical outcomes can be optimized by using PRP preparations that contain a higher concentration of platelets. Further research is needed to continue to optimize the composition of PRP used to treat patients with lumbar disc disease.

Intradiscal oxygen-ozone therapy for the treatment of symptomatic lumbar disc herniation: A preliminary study.

PURPOSE: To assess safety and effectiveness of computed tomography (CT)-guided intradiscal oxygen-ozone therapy (O2-O3 therapy) for the treatment of symptomatic lumbar disc herniation and radiological changes. MATERIALS AND METHODS: This study was conducted in twenty patients presenting lumbar disc herniation with resistant lumbar or lumbar radicular pain They underwent intradiscal oxygen-ozone therapy under CT guidance. They were treated at one- or two-disc levels, representing a total of 24 discs treated. MR imaging examinations were obtained before treatment and 2 months post-procedure to analyse treatment-related disc modifications including modification of the surfaces of the disc and of the herniated disc, and the variations in disc height according to the disc height index. Clinical outcomes were assessed using the visual analogue scale (VAS) to evaluate the severity of pain before the procedure, at primary (2 months) and at secondary (12 months) follow-ups. RESULTS: All the procedures were technically successful. The median VAS scores were 7.95 before the procedure, 3.9 at 2 months and 2.95 at 12 months. MRI analysis showed a significant decrease in herniation size at 2 months (-20%, p = 0.008). No immediate or late complications were observed. Only three patients (13.6%) underwent lumbar spine microdiscectomy in the year following ozone therapy. The treatment appeared to be more effective in cases of nerve root symptomatology. CONCLUSION: This study suggests that intradiscal O2-O3 therapy is safe and effective for the treatment of lumbar disc herniation associated with resistant lumbar or lumbar radicular pain.

Multicenter Retrospective Analysis of Intradiscal Condoliase Injection Therapy for Lumbar Disc Herniation.

Background and Objectives: Intradiscal injection of Condoliase (chondroitin sulfate ABC endolyase), a glycosaminoglycan-degrading enzyme, is employed as a minimally invasive treatment for lumbar disc herniation (LDH) and represents a promising option between conservative treatment and surgical intervention. Since its 2018 approval in Japan, multiple single-site trails have highlighted its effectiveness, however, the effect of LDH types, and influences of patient age, sex, etc., on treatment success remains unclear. Moreover, data on teenagers and elderly patients has not been reported. In this retrospective multi-center study, we sought to classify prognostic factors for successful condoliase treatment for LDH and assess its effect on patients < 20 and ≥70 years old. Materials and Methods: We reviewed the records of 137 LDH patients treated through condoliase at four Japanese institutions and assessed its effectiveness among different age categories on alleviation of visual analog scale (VAS) of leg pain, low back pain and numbness, as well as ODI and JOA scores. Moreover, we divided them into either a "group-A" category if a ≥50% improvement in baseline leg pain VAS was observed or "group-N" if VAS leg pain improved <50%. Next, we assessed the differences in clinical and demographic distribution between group-A and group-N. Results: Fifty-five patients were classified as group-A (77.5%) and 16 patients were allocated to group-N (22.5%). A significant difference in Pfirrmann classification was found between both cohorts, with grade IV suggested to be most receptive. A posterior disc angle > 5° was also found to approach statical significance. In all age groups, average VAS scores showed improvement. However, 75% of adolescent patients showed deterioration in Pfirrmann classification following treatment. Conclusions: Intradiscal condoliase injection is an effective treatment for LDH, even in patients with large vertebral translation and posterior disc angles, regardless of age. However, since condoliase imposes a risk of progressing disc degeneration, its indication for younger patients remains controversial.

Transforaminal epidural steroid injection combined with radio frequency for the treatment of lumbar disc herniation: a 2-year follow-up.

BACKGROUND: To assess the therapeutic efficacy of transforaminal epidural steroid injection (TFESI) combined with radio frequency (RF) for the treatment of lumbar disc herniation (LDH). METHODS: A total of 230 patients participated in the study: TFESI (Group T, n = 110), TFESI combined with RF (Group TR, n = 120). Visual analogue scale (VAS), Oswestry disability index (ODI) and Global perceived effect (GPE) scale were measured pre-operation, 1, 3, 6, 12 and 24 months after the operation. Hospitalization time, treatment time, complications, and recurrence were compared between the two groups. RESULTS: The VAS and ODI at each observation point of the post-operation were significantly decreased compared with the pre-operation in both groups (P < 0.05). There was no statistically difference of VAS and ODI between the two groups at 1 and 3 months of the post-operation (P > 0.05). However, The VAS and ODI scores in Group TR were significantly lower than that in Group T at 6, 12 and 24 months of the post-operation (P < 0.05). The GPE in group TR was high in the early days, while that at 1 and 3 months after treatment was significantly higher than that in group T (P < 0.05). The recurrence rate in Group TR was lower than that in Group T (P = 0.002). There was no significant difference in hospitalization time, complications, VAS and ODI score at the pre-operation between the two groups (P > 0.05). CONCLUSION: These findings suggest that TFESI combined with RF could effectively improve the pain and function, and had a long-term satisfactory effect for the treatment of LDH.

The effectiveness of chemonucleolysis with condoliase for treatment of painful lumbar disc herniation.

BACKGROUND: Chemonucleolysis with condoliase, which degrades chondroitin sulfate, could be a new, minimally invasive therapeutic option for patients with lumbar disc herniation (LDH). The purpose of this study was to analyze prognostic factors for clinical outcomes in LDH patients subjected to chemonucleolysis with condoliase. METHODS: Inclusion criteria for this procedure were 1) 18-70 years of age; 2) unilateral leg pain and positive straight leg raise (SLR) (<70°) or femoral nerve stretching test; 3) subligamentous extrusion verified on magnetic resonance imaging; 4) neurological symptoms consistent with a compressed nerve root on magnetic resonance imaging (MRI) images; and 5) minimum six months of follow-up. In total, 82 patients (55 men, 27 women; mean age, 47.2 ± 15.5 years; mean follow-up, 9.1 ± 3.0 months) who underwent chemonucleolysis with condoliase for painful LDH were included. An improvement of 50% or more in the Visual analogue scale (VAS) of leg pain was classified as effective. RESULTS: Seventy patients (85.4%) were classified into the effective (E) group and 12 patients (14.6%) into the less-effective (L) group. Surgical treatment was required in four patients. No severe adverse complications were reported; 41.3% of the patients developed disc degeneration of Pfirrmann grade 1 or more at the injected disc level. Univariate analysis revealed that young age (p = 0.036), without history of epidural or nerve root block (p = 0.024), and injection into the central portion of the intervertebral disc (p = 0.014) were significantly associated with clinical effectiveness. A logistic regression analysis revealed that injection into the central portion of the intervertebral disc (p = 0.049; odds ratio, 4.913; 95% confidence interval, 1.006-26.204) was significantly associated with clinical effectiveness. CONCLUSIONS: Chemonucleolysis with condoliase is a safe and effective treatment for painful LDH; 85.4% of the patients showed improvement after the treatment without severe adverse events. To obtain the best outcome, condoliase should be injected into the center of the intervertebral disc.

Clinical outcome of condoliase injection treatment for lumbar disc herniation: Indications for condoliase therapy.

BACKGROUND: Condoliase is a novel, potent chemonucleolytic drug available for clinical use for lumbar disc herniation (LDH) in Japan. The aim of this study was to assess the clinical outcome of condoliase therapy in patients with LDH, as well as factors affecting the clinical outcome. METHODS: We enrolled patients with LDH who were receiving condoliase injection. The following baseline data were collected: symptom duration; herniation level and type; T2 signal intensity of herniation; adverse events; rates of spondylolisthesis, posterior intervertebral angle of ≥5°, and vertebral body translation of ≥3 mm. Change in disc height, disc degeneration, herniation size, visual analog scale (VAS) for leg and back pain, and Oswestry Disability Index (ODI) were evaluated at the baseline, and 3-month follow-up. These data were compared between patients with efficacious (VAS improvement of ≥20 mm; group E) and inefficacious (VAS improvement <20 mm or required operation; group I) for condoliase treatment. RESULTS: Forty-seven patients (20 women, 27 men; mean age 48 years) were included. The herniation level was L2/3 in one patient, L3/4 in two, L4/5 in 23, and L5/S1 in 21. Median symptom duration was 8 months. The mean VAS and ODI improved significantly from the baseline to 3-month follow-up (p < 0.01). Group E included 33 patients (70.2%) and group I included 14, three of whom had a history of discectomy. The rates of spondylolisthesis and posterior intervertebral angle ≥5° were significantly higher in group I than in group E. However, the rates of trans-ligamentous type and herniation with high signal intensity on T2-weighted images (highT2) were significantly higher in group E. Reduction of disc herniation was more frequently observed in group E. CONCLUSIONS: Condoliase injection resulted in significantly improved symptoms in patients with LDH. Condoliase therapy was less effective for patients with a history of discectomy, spondylolisthesis, or those with a posterior intervertebral angle ≥5°, while trans-ligamentous type and high T2 herniation were associated with increased efficacy.

Ozone as Modulator of Resorption and Inflammatory Response in Extruded Nucleus Pulposus Herniation. Revising Concepts.

Ozone therapy has been used to treat disc herniation for more than four decades. There are several papers describing results and mechanism of action. However, it is very important to define the characteristics of extruded disc herniation. Although ozone therapy showed excellent results in the majority of spinal diseases, it is not yet fully accepted within the medical community. Perhaps it is partly due to the fact that, sometimes, indications are not appropriately made. The objective of our work is to explain the mechanisms of action of ozone therapy on the extruded disc herniation. Indeed, these mechanisms are quite different from those exerted by ozone on the protruded disc herniation and on the degenerative disc disease because the inflammatory response is very different between the various cases. Extruded disc herniation occurs when the nucleus squeezes through a weakness or tear in the annulus. Host immune system considers the nucleus material to be a foreign invader, which triggers an immune response and inflammation. We think ozone therapy modulates this immune response, activating macrophages, which produce phagocytosis of extruded nucleus pulposus. Ozone would also facilitate the passage from the M1 to M2 phase of macrophages, going from an inflammatory phase to a reparative phase. Further studies are needed to verify the switch of macrophages.

Long-term outcomes of transforaminal epidural steroid injection in patients with lumbosacral radicular pain according to the location, type, and size of herniated lumbar disc.

OBJECTIVES: Transforaminal epidural steroid injection (TFESI) is widely used to manage lumbosacral radicular pain due to herniated lumbar disc (HLD). OBJECTIVES: We evaluated the long-term outcomes of TFESI in patients with lumbosacral radicular pain due to an HLD by the location, type, and size of the HLD. METHODS: In total, 114 patients who received the initial TFESI at least 4 years ago completed a telephone interview. We investigated the presence of radicular pain, degree of current pain, current pain medications and TFESIs, additional TFESIs, progression to surgery, and trouble in performing daily life activities and occupational job duties. We classified the included patients by the location, type, and size of the HLD, and evaluated whether these factors affected the long-term outcomes of TFESI. RESULTS: At least 4 years after the initial TFESI, radicular pain was completely resolved in 45% of the patients. However, 30% patients were on oral painkillers or repetitive TFESIs or had undergone surgery and 15% had difficulty in performing daily life activities and occupational job duties. A larger number of patients with extruded lumbar disc herniation required additional TFESIs than those with protruded lumbar disc herniation. Apart from this, the outcomes did not significantly differ by the location, type, and size of the HLD. CONCLUSIONS: Our findings provide useful information to clinicians managing radicular pain due to HLD.