The Correlation of Epidural Fibrosis with Epiduroscopic and Radiologic Imaging for Chronic Pain after Back Surgery.

BACKGROUND: Chronic low back pain is observed frequently after lumbar spinal surgery. Epidural fibrosis has been implicated in the etiology of persistent pain after back surgery. The incidence of epidural fibrosis increases as the number and extent of spinal surgery increases. Epidural fibrosis can be detected by conventional radiologic methods [e.g., lumbosacral magnetic resonance imaging (MRI) with gadolinium], but these methods are insufficient to reveal the presence of epidural adhesions. Imaging of the epidural cavity using an epiduroscope is one of the best methods for visualizing the spinal cavity without damaging anatomic structures. OBJECTIVES: To evaluate the correlation between the type and number of surgery and the degree of epidural fibrosis and to compare epidural fibrosis in epiduroscopic and MRI findings in patients with failed back surgery syndrome (FBSS). STUDY DESIGN: A prospective trial. SETTING: A university hospital. METHODS: This study included 61 patients with persistent low back pain and/or radicular pain for at least 6 months, despite lumbar surgery and conservative treatment, and who accepted epiduroscopic imaging. All patients were evaluated in a physical examination using a visual analog scale (VAS) per the elapsed time after surgery. The patients were divided into 3 groups according to the number and type of surgeries. Epidural fibrosis was rated using MRI with gadolinium and epiduroscopy. RESULTS: When the relationship between admission symptoms and epidural fibrosis was evaluated, MRI findings of fibrosis were found to be significantly higher in all patients with both lumbar and radicular pain symptoms at the confidence level of 95% (P = 0.001). The degree of fibrosis detected using epiduroscopy was grade 1 and 2 in almost all patients who presented with low back pain only, only radicular pain, or only distal paresthesia (P = 0.001). In the correlation analysis between the duration of the postoperative period (4.13 ± 2.97 years) and the degree of fibrosis detected using MRI and epiduroscopy, a statistically significant relationship was found at the confidence level of 95% (P < 0.05). As the number and extent of spinal surgeries increased, the incidence of MRI fibrosis increased, which is compatible with the literature (P = 0.001) There was a statistically significant relationship between the degree of fibrosis as detected using MRI and epiduroscopy at the confidence level of 95% (P < 0.05). Differently, we observed that 6 patients had grade 1 fibrosis as diagnosed using epiduroscopy, whereas none had fibrosis on MRI. LIMITATIONS: We did not have a control group. Further studies are required to demonstrate the relevance of these 2 imaging techniques (epiduroscopy and MRI) in terms of detecting epidural fibrosis in patients with FBSS.  CONCLUSIONS: Epiduroscopic imaging seems to be more sensitive than MRI in detecting grade I epidural fibrosis in patients with FBSS. Thus, the possibility of low-grade epidural fibrosis as a source of pain after back surgery, should be kept in mind in normally reported MRIs. Treatment should be planned accordingly.

Neuromodulation for chronic pain.

Neuromodulation is an expanding area of pain medicine that incorporates an array of non-invasive, minimally invasive, and surgical electrical therapies. In this Series paper, we focus on spinal cord stimulation (SCS) therapies discussed within the framework of other invasive, minimally invasive, and non-invasive neuromodulation therapies. These therapies include deep brain and motor cortex stimulation, peripheral nerve stimulation, and the non-invasive treatments of repetitive transcranial magnetic stimulation, transcranial direct current stimulation, and transcutaneous electrical nerve stimulation. SCS methods with electrical variables that differ from traditional SCS have been approved. Although methods devoid of paraesthesias (eg, high frequency) should theoretically allow for placebo-controlled trials, few have been done. There is low-to-moderate quality evidence that SCS is superior to reoperation or conventional medical management for failed back surgery syndrome, and conflicting evidence as to the superiority of traditional SCS over sham stimulation or between different SCS modalities. Peripheral nerve stimulation technologies have also undergone rapid development and become less invasive, including many that are placed percutaneously. There is low-to-moderate quality evidence that peripheral nerve stimulation is effective for neuropathic pain in an extremity, low quality evidence that it is effective for back pain with or without leg pain, and conflicting evidence that it can prevent migraines. In the USA and many areas in Europe, deep brain and motor cortex stimulation are not approved for chronic pain, but are used off-label for refractory cases. Overall, there is mixed evidence supporting brain stimulation, with most sham-controlled trials yielding negative findings. Regarding non-invasive modalities, there is moderate quality evidence that repetitive transcranial magnetic stimulation does not provide meaningful benefit for chronic pain in general, but conflicting evidence regarding pain relief for neuropathic pain and headaches. For transcranial direct current stimulation, there is low-quality evidence supporting its benefit for chronic pain, but conflicting evidence regarding a small treatment effect for neuropathic pain and headaches. For transcutaneous electrical nerve stimulation, there is low-quality evidence that it is superior to sham or no treatment for neuropathic pain, but conflicting evidence for non-neuropathic pain. Future research should focus on better evaluating the short-term and long-term effectiveness of all neuromodulation modalities and whether they decrease health-care use, and on refining selection criteria and treatment variables.

Celecoxib-Loaded Electrospun Fibrous Antiadhesion Membranes Reduce COX-2/PGE2 Induced Inflammation and Epidural Fibrosis in a Rat Failed Back Surgery Syndrome Model.

To date, failed back surgery syndrome (FBSS) remains a therapy-refractory clinical condition after spinal surgery. The antiadhesion membrane is applied to prevent FBSS by isolating fibrosis; however, the inflammation stimulated by the foreign body and surgical trauma needs to be further resolved simultaneously. Therefore, we developed new electrospun polycaprolactone (PCL) fibrous membranes loaded with celecoxib (CEL) to prevent fibrosis and inflammation associated with FBSS. The CEL-loaded PCL fibers were randomly distributed, and the drug was released over two weeks. Fluorescence micrographs revealed that the fibroblasts proliferated less on the PCL-CEL fibrous membranes than in the PCL group and the blank control. In the rat laminectomy model after 4 weeks, magnetic resonance imaging of epidural fibrosis was least in the PCL-CEL group. Expression of COX-2 and PGE2 was lower in the PCL-CEL group. It concluded that the CEL-loaded PCL membrane could reduce fibrosis and inflammation in a rat model of FBSS via COX-2/PGE2 signaling pathways.

Metformin attenuates post-epidural fibrosis by inhibiting the TGF-ß1/Smad3 and HMGB1/TLR4 signaling pathways.

Excessive post-epidural fibrosis is a common cause of recurrent back pain after spinal surgery. Though various treatment methods have been conducted, the safe and effective drug for alleviating post-epidural fibrosis remains largely unknown. Metformin, a medicine used in the treatment of type 2 diabetes, has been noted to relieve fibrosis in various organs. In the present study, we aimed to explore the roles and mechanisms of metformin in scar formation in a mouse model of laminectomy. Post-epidural fibrosis developed in a mouse model of laminectomy by spinous process and the T12-L2 vertebral plate with a rongeur. With the administration of metformin, post-epidural fibrosis was reduced, accompanied with decreased collagen and fibronectin in the scar tissues. Mechanistically, metformin decreased fibronectin and collagen deposition in fibroblast cells, and this effect was dependent on the HMGB1/TLR4 and TGF-ß1/Smad3 signalling pathways. In addition, metformin influenced the metabolomics of the fibroblast cells. Taken together, our study suggests that metformin may be a potential option to mitigate epidural fibrosis after laminectomy.

Non-Union After Multiple Lumbar Fusion Surgeries in a Patient With Facioscapulohumeral Muscular Dystrophy: A Case Report and Review of the Literature.

BACKGROUND: Facioscapulohumeral muscular dystrophy (FSHD) is a rare condition affecting 1/20,000 persons and the third most common muscular dystrophy condition, with an autosomal dominant pattern of inheritance characterized by progressive muscular weakness primarily involving the face, shoulder girdle, and upper arm. The condition is associated with atrophic musculature of the trunk and core leading to difficulties with gait, posture, and function. FSHD leaves as many as 20% of patients wheelchair-bound and most commonly presents with low back, neck, and shoulder pain. CASE DESCRIPTION: We present the case of a patient with FSHD who underwent multiple spinal fusion surgeries without relief in her back pain. Imaging studies serve to highlight the extent of paraspinal muscle atrophy and provides the basis for a discussion on the preoperative factors that may predict patients most likely to benefit from surgery. We then provide a brief review of the literature on the role of paraspinal muscle atrophy in back pain. CONCLUSIONS: This case adds to our understanding of the surgical management of patients with FSHD and patients with atrophic core musculature as a whole.

An Evidence Based Review of Epidurolysis for the Management of Epidural Adhesions.

Purpose of Review: This review presents epidurolysis as a procedure to alleviate pain and disability from epidural adhesions. It reviews novel and groundbreaking evidence, describing the background, indications, benefits and adverse events from this procedure in an effort to provide healthcare experts with the data required to decide on an intervention for their patients. Recent Findings: Epidural adhesions (EA) or epidural fibrosis (EF) is defined as non-physiologic scar formation secondary to a local inflammatory reaction provoked by tissue trauma in the epidural space. Often, it is a sequelae of surgical spine intervention or instrumentation. The cost associated with chronic post-operative back pain has been reported to be up to nearly $12,500 dollars per year; this, coupled with the increasing prevalence of chronic lower back pain and the subsequent increase in surgical management of back pain, renders EF a significant cost and morbidity in the U.S. Though risk factors leading to the development of EA are not well established, epidural fibrosis has been reported to be the culprit in up to 46% of cases of Failed Back Surgery Syndrome (FBSS), a chronic pain condition found in up to 20-54% of patients who receive back surgery. Moreover, EF has also been associated with lumbar radiculopathy after lumbar disc surgery. Epidurolysis is defined as the mechanical dissolution of epidural fibrotic scar tissue for persistent axial spine or radicular pain due to epidural fibrosis that is refractory to conservative therapy Endoscopic lysis of adhesions is a procedural technique which has been shown to improve chronic back pain in one-third to one-half of patients with clinically symptomatic fibrous adhesions. Here we review some of the novel evidence that supports this procedure in EA and FBSS. Summary: The literature concerning epidurolysis in the management of epidural adhesions is insufficient. Prospective studies, including randomized controlled trials and observational studies, have suggested epidurolysis to be effective in terms of pain reduction, functional improvement, and patient satisfaction scores. Observational studies report epidurolysis as a well-tolerated, safe procedure. Current evidence suggests that epidurolysis may be used as an effective treatment modality for epidural adhesions. Nonetheless, further high quality randomized controlled studies assessing the safety and efficacy of epidurolysis in the management of epidural adhesions is needed.

Transforaminal Epiduroscopy in Patients with Failed Back Surgery Syndrome.

BACKGROUND: Epiduroscopy is a useful diagnostic and therapeutic tool for managing failed back surgery syndrome (FBSS). The conventional approach is via either the sacral hiatus or the interlaminar. Major causes of FBSS include epidural fibrosis, disc herniation, and stenosis. When these problems are located at the intervertebral foramen level, it can be difficult to reach the lateral recess and the foramen with the epiduroscope. Transforaminal epiduroscopy could be a useful alternative approach in patients with FBSS located at the foraminal level. OBJECTIVE: We present a new procedure for lumbar epiduroscopy via a transforaminal approach and its application in patients with FBSS. The technique is described and long-term results are reported. STUDY DESIGN: This study used a single-arm prospective observational design. SETTING: The research took place at the University Hospital in Spain. METHODS: Patients with FBSS suffering severe chronic radicular pain (Numeric Rating Scale [NRS-11] > 7) who had not responded to other treatments were included. Selective root stimulation during a pulsed radiofrequency procedure confirmed the origin of pain by means of an exact reproduction of typical pain. Transforaminal epiduroscopy was performed at the affected level. The severity of fibrosis observed was recorded. The NRS-11 score was reevaluated at 1, 6, and 12 months after the procedure. Any complications related to the treatment were recorded. RESULTS: Twenty-four patients were included. The mean number of back surgeries was 1.66 (range, 1-5). The basal NRS-11 score was 7.83 (0.14); at 1 month, 3.66 (0.38) (P < 0.001); at 6 months, 4.46 (0.48) (P < 0.01); and at 1 year after treatment, 4.17 (0.51) (P < 0.01). Most patients (54%; 95% CI, 34%-74%) obtained > 50% pain reduction on the NRS-11, maintained during a 1-year follow-up period. No major complications were registered. LIMITATIONS: The research was limited by the lack of a control group. CONCLUSIONS: We have described a new procedure for epiduroscopy via the transforaminal approach. It is a useful and safe approach to managing FBSS at the foraminal level and shows better long-term results than other endoscopic procedures. KEY WORDS: Epidural, epiduroscopy, chronic pain, spinal cord, back surgery.

Narcotic Addiction in Failed Back Surgery Syndrome.

Back pain is a common health problem that reduces the quality of life for human beings worldwide. Several treatment modalities have been reported as effective for pain relief. Generally, patients often undergo surgical interventions as pain becomes intractable, after conservative treatment. With advances in surgical techniques, those choosing spinal surgery as an option have increased over time, and instrumentation is more popular than it was years ago. However, some patients still have back pain after spinal operations. The number of patients classified as having failed back surgery syndrome (FBSS) has increased over time as has the requirement for patients receiving long-term analgesics. Because pain relief is regarded as a human right, narcotics were prescribed more frequently than before. Narcotic addiction in patients with FBSS has become an important issue. Here, we review the prevalence of FBSS, the mechanism of narcotic addiction, and their correlations. Additionally, several potentially effective strategies for the prevention and treatment of narcotic addiction in FBSS patients are evaluated and discussed.

Salience, central executive, and sensorimotor network functional connectivity alterations in failed back surgery syndrome.

OBJECTIVE: This study examined the altered patterns of functional connectivity in task-positive resting state networks in failed back surgery syndrome (FBSS) patients compared to healthy controls using functional magnetic resonance imaging (fMRI). This work stems from a previous study in which alterations in the task-negative default mode network were investigated. DESIGN: Participants underwent a 7-minute resting state fMRI scan in which they lay still, with eyes closed, in the absence of a task. SETTING: Scanning took place at the National Research Council's 3Tesla MRI magnet in Winnipeg, Canada. SUBJECTS: Fourteen patients with FBSS and age- and gender-matched controls participated in this study. Three patients were removed from the analyses due to image artefact (n=1) and effective pain treatment (n=2). Eleven patients (5 female, mean age 52.7 years) and their matched controls were included in the final analyses. METHODS: Resting state fMRI data were analyzed using an independent component analysis, yielding three resting state networks of interest: the salience network (SN), involved in detection of external stimuli, central executive network (CEN), involved in cognitions, and sensorimotor network (SeN), involved in sensory and motor integration. Analysis of Variance contrasts were performed for each network, comparing functional connectivity differences between FBSS patients and healthy controls. RESULTS: Alterations were observed in all three resting state networks, primarily relating to pain and its processing in the FBSS group. Specifically, compared to healthy controls, FBSS patients demonstrated increased functional connectivity in the anterior cingulate cortex within the SN, medial frontal gyrus in the CEN, and precentral gyrus within the SeN. FBSS patients also demonstrated decreased functional connectivity in the medial frontal gyrus in the SeN compared to healthy controls. Interestingly, we also observed internetwork functional connectivity in the SN and SeN. CONCLUSIONS: FBSS is associated with altered patterns of functional connectivity in the SN, CEN, and SeN. Taken together with our previous work, this reveals that a chronic pain condition can have a dramatic effect on the connectivity of multiple resting state networks. IMPLICATIONS: These data suggest that a chronic pain condition-FBSS-is associated with disruptions to networks of functional connectivity in brain areas that are involved in numerous functions, including pain processing, sensation, and movement. It is possible that the alterations in these networks may contribute to other common chronic pain comorbidities, such as disrupted cognitions or anxiety. Previous research shows that during experimentally-induced pain, these networks can return to initial levels of functioning, indicating that these functional alterations are likely not permanent.

Evaluation of spinal cord stimulation on the symptoms of anxiety and depression and pain intensity in patients with failed back surgery syndrome.

BACKGROUND: Spinal cord stimulation (SCS) is now established as the primary treatment for failed back surgery syndrome (FBSS). Commonly, patients with chronic pain and FBSS often report symptoms of anxiety and depression resulting from this condition. These factors can modulate and amplify the pain experience, therefore, further challenging treatment success. AIMS: This study examined the efficacy of SCS on alleviating the symptoms of anxiety and depression associated with chronic pain as well as pain intensity in a group of patients with FBSS. METHODS: A convenience sample (n = 26) was selected for participation. Questionnaires [Hospital Anxiety and Depression Scale (HADS) and Brief Pain Inventory Short Form (BPI-SF)] were completed and examined pre and post spinal cord implant. RESULTS: Analysis of the data 1 year following SCS indicates that there was a statistical significant improvement in the symptoms of depression and anxiety reported as well as pain intensity in all participants (p < 0.001). Both anxiety and depression scores on the HADS were significantly lower compared to baseline (p < 0.001). Pain intensity scores decreased by ≥50% from baseline in all participants. Opioid analgesia was discontinued by 90% (n = 8) of participants. CONCLUSION: Whilst it is already recognised that SCS reduces pain in FBSS, this study demonstrated that it also reduced the symptoms of anxiety and depression with an associated reduction in opioid consumption.

Mitomycin C induces fibroblasts apoptosis and reduces epidural fibrosis by regulating miR-200b and its targeting of RhoE.

Mitomycin C (MMC) is known to reduce epidural fibrosis, but the underlying mechanisms have not yet been elucidated. Aberrant miR-200b expressions have been reported in multiple types of fibrotic tissues from many diseases. The aim of this study was to clarify the mechanism by which MMC induces fibroblasts apoptosis and reduces epidural fibrosis. The expression of miR-200b in human fibroblasts was determined after MMC treatment, and the targeted association between miR-200b and RhoE was determined using the luciferase activity assay. The effects of MMC and miR-200b on human fibroblasts apoptosis were evaluated using flow cytometry and western blot analysis. The effects of MMC and miR-200b on epidural fibrosis were evaluated using the Rydell classification, hydroxyproline content, apoptotic cell count and histological analysis. The study revealed that MMC could significantly downregulate miR-200b expression and induce human fibroblasts apoptosis. The direct downregulation of miR-200b could induce human fibroblasts apoptosis. Furthermore, we identified the binding sequence for miR-200b within the 3' untranslated region of RhoE. RhoE was confirmed to be a direct target of miR-200b, and RhoE itself acted as a promoter of fibroblasts apoptosis. The inhibition of miR-200b increased fibroblasts apoptosis and reduced epidural fibrosis in rats, which was in accordance with the effect of MMC. This study suggests that MMC induces fibroblasts apoptosis and reduces epidural fibrosis by regulating miR-200b expression and its targeting of RhoE.

Anatomy, physiology and neurobiology of the nociception: a focus on low back pain (part A).

INTRODUCTION: The treatment of Failed Back Surgery Syndrome (FBSS) remains a challenge for pain medicine due to the complexity in the interactions between [1] a residual mechanical pain after surgery and, [2] a progressive transition into chronic pain involving central nervous system plasticity and molecular reorganization. The aim of this paper is to provide a fundamental overview of the pain pathway supporting the nociceptive component of the back pain. METHODS: Literature searches included an exhaustive review of 643 references and 74 book chapters updated by searching the major electronic databases from 1930 to August 2013. RESULTS: Pain input is gathered by the peripheral fibre from the innervated tissue's environment and relayed by two contiguous central axons to the brain, via the spinal cord. At this level, it is possible to characterize physical pain and emotional pain. These are supported by two different pathways, encoding two dimensions of pain perception: In Neo-spino-thalamic pathway, the wide dynamic range neuron system is able to provide the information needed for mapping the "sensory-discriminative" dimension of pain. The second projection system (Paleo-spino-thalamic pathway) also involves the ventromedial thalamus but projects to the amygdala, the insula and the anterior cingulate cortex. These areas are associated with emotionality and affect. CONCLUSION: The mechanical component of FBSS cannot be understood unless the functioning of the pain system is known. But ultimately, the highly variable nature of back pain expression among individuals would require a careful pathophysiological dissection of the potential generators of back pain to guide pain management strategies.

Pathophysiological characterisation of back pain generators in failed back surgery syndrome (part B).

INTRODUCTION: Low back surgery, including as many type of spine procedures as the multitude of failed back surgery syndrome (FBSS) etiologies, is not always the answer for patients with chronic low back pain. Paradoxically, although a patient is considered to present FBSS because he has already undergone spinal surgery, any new symptom in the back or deterioration of back pain must not be immediately attributed to FBSS, but could be related to another cause independently of the initial mechanical problem. The aim of this paper is to extensively review the potential back pain generators in FBSS patients and to discuss their respective roles and interactions in back pain pathophysiology. METHODS: Literature searches included an exhaustive review of 643 references and 74 book chapters updated by searching the major electronic databases from 1930 to August 2013. RESULTS: Nociceptive fibres innervating any of the back anatomical structures can all play a part in the pathogenesis of the low back pain component in FBSS. The main spinal pain generators are not only myofascial syndrome or muscle spasm but also the facets, the disc complex or a sagittal imbalance and should therefore be carefully reviewed. Only after these steps and appropriate imaging, would it be justified to irremediably diagnose the patient with a refractory chronic condition, requiring no further spine surgery and to propose "palliative" pain treatment options. CONCLUSION: Clinical investigations of the low back pain component in FBSS patients should be based on meticulous dissection of all potential triggers that could be a source of the nociceptive pain characteristics and possibly amenable to further aetiological treatment. Clinicians should therefore refine pain management strategies to ensure that the chronic nature of the pain becomes the guiding principle for multidisciplinary assessment.

New insights from immunohistochemistry for the characterization of epidural scar tissue.

BACKGROUND: The association between epidural fibrosis and recurrent symptoms after lumbar spine surgery remains a matter of debate in scientific literature and the underlying pathophysiological mechanism has not been clearly elucidated. OBJECTIVE: To investigate the presence of nerve fibers and the expression of osteopontin in epidural fibrous tissue after lumbar surgery in humans. STUDY DESIGN: Laboratory study of human tissue samples. METHODS: Twenty-four patients with persistent or recurrent low back and/or leg pain after lumbar spine surgery, in whom no relevant findings were present on magnetic resonance imaging (MRI) besides epidural scar tissue, were submitted to epiduroscopy. Biopsy samples of epidural scar tissue resting in the posterior epidural and periradicular space were obtained from 15 patients, using an endoscopic grasping forceps, in locations where the stimulation with the tip of a Fogarty consistently reproduced pain. Biopsy samples were processed for examination under optical and transmission electron microscopes and under a fluorescence microscope after incubation in primary antibodies against beta3-tubulin or against osteopontin. RESULTS: Optical and transmission electron microscopy revealed a homogeneous fibrous tissue rich in collagen and lacking nerve fibers. No immunofluorescence was present in any of the samples immunoreacted against beta3-tubulin. In the samples immunoreacted against osteopontin, a punctate signal was detected around the collagen fibers. LIMITATIONS: Being a human study, there was no control group, so it is not possible to determine the contribution of osteopontin in the formation of epidural fibrosis and its relation to the patients' symptoms. Additional animal studies are needed to investigate these issues. CONCLUSION: Rather than direct stimulation of nociceptors in the epidural scar tissue, other factors should relate epidural fibrosis and recurrent symptoms after lumbar spine surgery. Osteopontin seems to play a role in the formation of epidural fibrosis.

Epidural adhesiolysis: an evidence-based review.

First described over 25 years ago, epidural lysis of adhesions (LOA) involves the mechanical dissolution of epidural scar tissue, which may directly alleviate pain and facilitate the spread of analgesic substances to area(s) of pain generation. Although it most commonly performed for lumbar failed back surgery syndrome, there is a growing body of evidence that suggests it may be effective for spinal stenosis and radicular pain stemming from a herniated disc. There is weak positive evidence that LOA is more effective than conventional caudal epidural steroid injections for failed back surgery syndrome and spinal stenosis, and that LOA is more effective than sham adhesiolysis and conservative management for lumbosacral radiculopathy. For cervical disc herniation and spinal stenosis, there is only anecdotal evidence suggesting effectiveness and safety. Factors that may contribute to the enhanced efficacy compared to traditional epidural steroid administration include the high volume administered, the use of hypertonic saline, and to a lesser extent the use of hyaluronidase and a navigable catheter to mechanically disrupt scar tissue and guide medication administration. Although LOA is widely considered a safe intervention, the complication rates are higher than for conventional epidural steroid injection.

Default mode network functional connectivity altered in failed back surgery syndrome.

UNLABELLED: The purpose of this study was to identify alterations in the default mode network of failed back surgery syndrome patients as compared to healthy subjects. Resting state functional magnetic resonance imaging was conducted at 3 Tesla and data were analyzed with an independent component analysis. Results indicate an overall reduced functional connectivity of the default mode network and recruitment of additional pain modulation brain regions, including dorsolateral prefrontal cortex, insula, and additional sensory motor integration brain regions, including precentral and postcentral gyri, for failed back surgery syndrome patients. PERSPECTIVE: This article presents alterations in the default mode network of chronic low back pain patients with failed back surgery syndrome as compared to healthy participants.