Epidural Interventions in the Management of Chronic Spinal Pain: American Society of Interventional Pain Physicians (ASIPP) Comprehensive Evidence-Based Guidelines.

BACKGROUND: Chronic spinal pain is the most prevalent chronic disease with employment of multiple modes of interventional techniques including epidural interventions. Multiple randomized controlled trials (RCTs), observational studies, systematic reviews, and guidelines have been published. The recent review of the utilization patterns and expenditures show that there has been a decline in utilization of epidural injections with decrease in inflation adjusted costs from 2009 to 2018. The American Society of Interventional Pain Physicians (ASIPP) published guidelines for interventional techniques in 2013, and guidelines for facet joint interventions in 2020. Consequently, these guidelines have been prepared to update previously existing guidelines. OBJECTIVE: To provide evidence-based guidance in performing therapeutic epidural procedures, including caudal, interlaminar in lumbar, cervical, and thoracic spinal regions, transforaminal in lumbar spine, and percutaneous adhesiolysis in the lumbar spine. METHODS: The methodology utilized included the development of objective and key questions with utilization of trustworthy standards. The literature pertaining to all aspects of epidural interventions was viewed with best evidence synthesis of available literature and recommendations were provided. RESULTS: In preparation of the guidelines, extensive literature review was performed. In addition to review of multiple manuscripts in reference to utilization, expenditures, anatomical and pathophysiological considerations, pharmacological and harmful effects of drugs and procedures, for evidence synthesis we have included 47 systematic reviews and 43 RCTs covering all epidural interventions to meet the objectives.The evidence recommendations are as follows: Disc herniation: Based on relevant, high-quality fluoroscopically guided epidural injections, with or without steroids, and results of previous systematic reviews, the evidence is Level I for caudal epidural injections, lumbar interlaminar epidural injections, lumbar transforaminal epidural injections, and cervical interlaminar epidural injections with strong recommendation for long-term effectiveness.The evidence for percutaneous adhesiolysis in managing disc herniation based on one high-quality, placebo-controlled RCT is Level II with moderate to strong recommendation for long-term improvement in patients nonresponsive to conservative management and fluoroscopically guided epidural injections. For thoracic disc herniation, based on one relevant, high-quality RCT of thoracic epidural with fluoroscopic guidance, with or without steroids, the evidence is Level II with moderate to strong recommendation for long-term effectiveness.Spinal stenosis: The evidence based on one high-quality RCT in each category the evidence is Level III to II for fluoroscopically guided caudal epidural injections with moderate to strong recommendation and Level II for fluoroscopically guided lumbar and cervical interlaminar epidural injections with moderate to strong recommendation for long-term effectiveness.The evidence for lumbar transforaminal epidural injections is Level IV to III with moderate recommendation with fluoroscopically guided lumbar transforaminal epidural injections for long-term improvement. The evidence for percutaneous adhesiolysis in lumbar stenosis based on relevant, moderate to high quality RCTs, observational studies, and systematic reviews is Level II with moderate to strong recommendation for long-term improvement after failure of conservative management and fluoroscopically guided epidural injections. Axial discogenic pain: The evidence for axial discogenic pain without facet joint pain or sacroiliac joint pain in the lumbar and cervical spine with fluoroscopically guided caudal, lumbar and cervical interlaminar epidural injections, based on one relevant high quality RCT in each category is Level II with moderate to strong recommendation for long-term improvement, with or without steroids. Post-surgery syndrome: The evidence for lumbar and cervical post-surgery syndrome based on one relevant, high-quality RCT with fluoroscopic guidance for caudal and cervical interlaminar epidural injections, with or without steroids, is Level II with moderate to strong recommendation for long-term improvement. For percutaneous adhesiolysis, based on multiple moderate to high-quality RCTs and systematic reviews, the evidence is Level I with strong recommendation for long-term improvement after failure of conservative management and fluoroscopically guided epidural injections. LIMITATIONS: The limitations of these guidelines include a continued paucity of high-quality studies for some techniques and various conditions including spinal stenosis, post-surgery syndrome, and discogenic pain. CONCLUSIONS: These epidural intervention guidelines including percutaneous adhesiolysis were prepared with a comprehensive review of the literature with methodologic quality assessment and determination of level of evidence with strength of recommendations

The Role of Cortisol in Chronic Stress, Neurodegenerative Diseases, and Psychological Disorders

Cortisol, a critical glucocorticoid hormone produced by the adrenal glands, plays a pivotal role in various physiological processes. Its release is finely orchestrated by the suprachiasmatic nucleus, governing the circadian rhythm and activating the intricate hypothalamic–pituitary–adrenal (HPA) axis, a vital neuroendocrine system responsible for stress response and maintaining homeostasis. Disruptions in cortisol regulation due to chronic stress, disease, and aging have profound implications for multiple bodily systems. Animal models have been instrumental in elucidating these complex cortisol dynamics during stress, shedding light on the interplay between physiological, neuroendocrine, and immune factors in the stress response. These models have also revealed the impact of various stressors, including social hierarchies, highlighting the role of social factors in cortisol regulation. Moreover, chronic stress is closely linked to the progression of neurodegenerative diseases, like Alzheimer’s and Parkinson’s, driven by excessive cortisol production and HPA axis dysregulation, along with neuroinflammation in the central nervous system. The relationship between cortisol dysregulation and major depressive disorder is complex, characterized by HPA axis hyperactivity and chronic inflammation. Lastly, chronic pain is associated with abnormal cortisol patterns that heighten pain sensitivity and susceptibility. Understanding these multifaceted mechanisms and their effects is essential, as they offer insights into potential interventions to mitigate the detrimental consequences of chronic stress and cortisol dysregulation in these conditions

Comparative safety review of current treatment options for chronic low back pain and unmet needs: a narrative review

Introduction: The healthcare expenditures in the United States are substantial for the management of refractory, chronic low back pain (CLBP). The objective of this review is to summarize and evaluate the safety profiles of different pharmacological treatment options used in the management of CLBP. Areas covered: The authors conducted a search of randomized controlled trials (RCTs) assessing the safety profiles of different pharmacological agents used in the management of CLBP. This narrative review covered corticosteroids, opioids, antidepressants, gabapentinoids, nonsteroidal anti-inflammatory drugs, muscle relaxants, anti-nerve growth factor antibodies and topical agents, as monotherapy or in combination. Expert opinion: The risk-benefit ratio of a particular treatment is a subject driving the ongoing development of pharmaceuticals. The most commonly reported AEs across all drug classes are of gastrointestinal nature, followed by neurological and skin-related. These AEs include nausea, dizziness, constipation, arthralgia, headache, dry mouth, pruritus, etc. The majority of the AEs reported are not life-threatening, although they may lower patients\u27 quality of life, thus, affecting their compliance. One of the biggest limitations of our review stems from the paucity of safety assessments in published RCTs. Advances in our understanding of the neurobiology of pain will promote development of new therapeutic strategies

Can Implementation of Genetics and Pharmacogenomics Improve Treatment of Chronic Low Back Pain?

Etiology of back pain is multifactorial and not completely understood, and for the majority of people who suffer from chronic low back pain (cLBP), the precise cause cannot be determined. We know that back pain is somewhat heritable, chronic pain more so than acute. The aim of this review is to compile the genes identified by numerous genetic association studies of chronic pain conditions, focusing on cLBP specifically. Higher-order neurologic processes involved in pain maintenance and generation may explain genetic contributions and functional predisposition to formation of cLBP that does not involve spine pathology. Several genes have been identified in genetic association studies of cLBP and roughly, these genes could be grouped into several categories, coding for: receptors, enzymes, cytokines and related molecules, and transcription factors. Treatment of cLBP should be multimodal. In this review, we discuss how an individual\u27s genotype could affect their response to therapy, as well as how genetic polymorphisms in CYP450 and other enzymes are crucial for affecting the metabolic profile of drugs used for the treatment of cLBP. Implementation of gene-focused pharmacotherapy has the potential to deliver select, more efficacious drugs and avoid unnecessary, polypharmacy-related adverse events in many painful conditions, including cLBP

Role of percutaneous neurolysis in lumbar disc herniation: systematic review and meta-analysis

Background: Recalcitrant disc herniation may result in chronic lumbar radiculopathy or sciatica. Fluoroscopically directed epidural injections and other conservative modalities may provide inadequate improvement in some patients. In these cases, percutaneous neurolysis with targeted delivery of medications is often the next step in pain management. Methods: An evidence-based system of methodologic assessment, namely, the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) was used. Multiple databases were searched from 1966 to January 2021. Principles of the best evidence synthesis were incorporated into qualitative evidence synthesis. The primary outcome measure was the proportion of patients with significant pain relief and functional improvement (≥ 50%). Duration of relief was categorized as short-term (\u3c 6 months) and long-term (≥ 6 months). Results: This assessment identified one high-quality randomized controlled trial (RCT) and 5 moderate-quality non-randomized studies with an application of percutaneous neurolysis in disc herniation. Overall, the results were positive, with level II evidence. Conclusions: Based on the present systematic review, with one RCT and 5 nonrandomized studies, the evidence level is II for percutaneous neurolysis in managing lumbar disc herniation

Efficacy of Percutaneous Adhesiolysis in Managing Low Back and Lower Extremity Pain: A Systematic Review and Meta-analysis of Randomized Controlled Trials

Abstract Introduction Chronic refractory low back and lower extremity pain recalcitrant to conservative management and epidural injections secondary to postsurgery syndrome, spinal stenosis, and disc herniation are sometimes managed with percutaneous adhesiolysis. Consequently, this systematic review and meta-analysis was undertaken to assess the efficacy of percutaneous adhesiolysis in managing low back and lower extremity pain. Methods A systematic review and meta-analysis of randomized controlled trials (RCTs) utilizing the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist was performed. A comprehensive literature search of multiple databases from 1966 to July 2022, including manual searches of the bibliography of known review articles was performed. Quality assessment of the included trials, meta-analysis, and best evidence synthesis was performed. The primary outcome measure was a significant reduction in pain (short term up to 6 months and long term more than 6 months). Results The search identified 26 publications, with 9 trials meeting the inclusion criteria. The results of dual-arm and single-arm analyses showed significant improvement in pain and function at 12 months. Opioid consumption was also significantly reduced at 6 months with dual-arm analysis, whereas single-arm analysis showed a significant decrease from baseline to treatment at the 3-, 6-, and 12-month analyses. At 1 year follow-up, seven of seven trials were positive for improvements in pain relief, function, and diminution of opioid use. Discussion Based on the present systematic review of nine RCTs, the evidence level is I to II, with moderate to strong recommendation for percutaneous adhesiolysis in managing low back and lower extremity pain. The limitations of the evidence include paucity of literature, lack of placebo-controlled trials, and the majority of the trials studying post lumbar surgery syndrome. Conclusion The evidence is level I to II or strong to moderate based on five high-quality and two moderate-quality RCTs, with 1 year follow-up that percutaneous adhesiolysis is efficacious in the treatment of chronic refractory low back and lower extremity pain

Epidural injections for lumbar radiculopathy or sciatica: a comparative systematic review and meta-analysis of cochrane review

BACKGROUND: Epidural injections are one of the commonly performed procedures in managing low back and lower extremity pain. In the past, Pinto et al and Chou et al performed systematic reviews and meta-analyses with a recent update from Oliveira et al showing lack of effectiveness of epidural steroid injections in managing lumbar radiculopathy. In contrast, multiple other systematic reviews and meta-analyses have supported the efficacy and use of epidural injections utilizing fluoroscopic guidance. STUDY DESIGN: A systematic review and meta-analysis of randomized controlled trials (RCTs) of epidural injections in managing chronic low back and lower extremity pain with sciatica or lumbar radiculopathy. OBJECTIVES: To assess the efficacy of 3 categories of epidural injections for lumbar radiculopathy or sciatica performed utilizing saline with steroids, local anesthetic alone, or steroids with local anesthetic. METHODS: In this systematic review and meta-analysis, RCTs with a placebo control or an active control design, performed under fluoroscopic guidance, with at least 6 months of followed-up were included. The outcome measures were pain relief and functional status improvement. Significant improvement was defined as 50% or greater pain relief and functional status improvement. Literature search was performed through January 2021. Methodological quality assessments were performed. Evidence was summarized utilizing principles of best evidence synthesis. RESULTS: In this analysis, a total of 21 RCTs were utilized with at least 6 months of follow-up and performed under fluoroscopic guidance. However, only 6 of 25 trials from Cochrane review met inclusion criteria for this review. Based on qualitative analysis, of the 21 trials included in the present analysis, there was only one placebo-controlled trial found to be negative. With conventional meta-analysis, there was no significant difference among the studies because all of the studies were active control with local anesthetic or local anesthetic and steroids. Further, with single-arm analysis, of the 5 trials included in that portion of the study, significant improvement was seen with local anesthetic alone compared to local anesthetic and steroids. There was a tendency for better improvement with steroids in terms of both pain relief and functional status. The level of evidence is Level I or strong for local anesthetic with steroids and Level I to II or moderate to strong for local anesthetic as a single agent based on multiple relevant high quality RCTs. LIMITATIONS: Despite multiple trials available, there is a paucity of true RCTs performed under fluoroscopic guidance with any of the approaches. CONCLUSION: Epidural injections with or without steroids for radiculopathy showed significant effectiveness with Level I or strong evidence for local anesthetic with steroids and Level II to I or moderate to strong evidence with local anesthetic alone

Systematic review and meta-analysis of effectiveness of therapeutic sacroiliac joint injections

Background:The sacroiliac joint is one of the proven causes of low back and lower extremity pain, ranging from 10% to 25% in patients with persistent axial low back pain without disc herniation, discogenic pain, or radiculitis. Despite the difficulty of diagnosis, multiple therapeutic modalities including surgical and nonsurgical interventions have been utilized. Among the interventional modalities, intraarticular injections are commonly utilized. Objective:To evaluate the therapeutic effectiveness of intraarticular injections in the sacroiliac joint. Study design:A systematic review and meta-analysis of randomized controlled trials (RCTs) and observational studies of the therapeutic effectiveness of intraarticular injections of the sacroiliac joint utilizing the Preferred Reporting Items For Systematic Reviews And Meta-Analyses (PRISMA) checklist. Methods:The available literature on therapeutic sacroiliac joint intraarticular injections was reviewed. The quality assessment criteria utilized were the Cochrane review criteria to assess risk of bias, the Interventional Pain Management Techniques - Quality Appraisal of Reliability and Risk of Bias Assessment (IPM-QRB) for randomized therapeutic trials, and the Interventional Pain Management Techniques - Quality Appraisal of Reliability and Risk of Bias Assessment for Nonrandomized Studies (IPM-QRBNR) for nonrandomized studies. The level of evidence was based on best evidence synthesis with modified grading of qualitative evidence from Level I to Level V. Data collection was performed including literature published from 1966 through December 2022, as well as manual searches of the bibliographies of known articles. Outcome measures:Primary outcome measures include pain relief and improvement in functional status at 3 months for a single intervention. Only the studies performed under fluoroscopic guidance, with at least 3 months of follow-up were included. Duration of relief was categorized as short-term (\u3c 6 months) and long-term (\u3e 6 months). Results:Based on the qualitative and quantitative analyses with a single-arm meta-analysis and the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) system of appraisal, and the inclusion of 11 RCTs (5 positive, 6 negative) and 3 observational studies (2 positive, one negative), the evidence was Level III or fair in managing low back pain of sacroiliac joint origin with sacroiliac joint injections. Limitations:This systematic review and meta-analysis are limited by lack of eligible studies, inconsistencies among the available studies, variations in techniques, variable diagnostic standards for inclusion criteria, and finally, the inability to correlate the results and perform an optimal systematic review and meta-analysis. Conclusion:The present systematic review and meta-analysis show an inability to perform conventional dual-arm analysis, whereas a single-arm meta-analysis demonstrated a difference of approximately 3 points on the Numeric Rating Scale (NRS) and 8 points on the Oswestry Disability Index (ODI). However, there were no studies that considered \u3e= 50% relief as the criterion standard. Overall, the qualitative and quantitative evidence combined shows Level III or fair evidence for therapeutic sacroiliac joint injections for managing low back pain of sacroiliac joint origin

Medial branch blocks and the effectiveness of radiofrequency neurotomy in managing chronic thoracic pain: A systematic review and meta-analysis

Background:Extensive research into potential sources of thoracic pain with or without referred pain into the chest wall has demonstrated that thoracic facet joints can be a potential source of pain confirmed by precise, diagnostic blocks.The objective of this systematic review and meta-analysis is to evaluate the effectiveness of medial branch blocks and radiofrequency neurotomy as a therapeutic thoracic facet joint intervention. Methods:Systematic review and meta-analysis of randomized controlled trials (RCTs) and observational studies of medial branch blocks and the radiofrequency neurotomy in managing thoracic pain utilizing the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist was performed. A comprehensive literature search of multiple databases of RCTs and observational studies of medial branch blocks and radiofrequency neurotomy in managing chronic thoracic pain were identified from 1996 to December 2022 with inclusion of manual searches of the bibliography of known review articles and multiple databases. Methodologic quality and risk of bias assessment was also conducted. Evidence was synthesized utilizing principles of quality assessment and best evidence synthesis, with conventional and single meta-analysis. The primary outcome measure of success was 3 months of pain reduction for medial branch blocks and 6 months for radiofrequency thermoneurolysis for a single treatment. Short-term success was defined as up to 6 months and long-term was more than 6 months. Results:This literature search yielded 11 studies meeting the inclusion criteria, of which 3 were RCTs and 8 were observational studies. Of the 3 RCTs, 2 of them assessed medial branch blocks and one trial assessed radiofrequency for thoracic pain. The evidence for managing thoracic pain with qualitative analysis and single-arm meta-analysis and GRADE system of appraisal, with the inclusion of 2 RCTs and 3 observational studies for medial branch blocks was Level II. For radiofrequency neurotomy, with the inclusion of one RCT of 20 patients in the treatment group and 5 observational studies, the evidence was Level III in managing thoracic pain. Limitations:There was a paucity of literature with RCTs and real-world pragmatic controlled trials. Even observational studies had small sample sizes providing inadequate clinically applicable results. In addition, there was heterogeneity of the available studies in terms of their inclusion and exclusion criteria, defining their endpoints and the effectiveness of the procedures. Conclusion:This systematic review and meta-analysis show Level II evidence of medial branch blocks and Level III evidence for radiofrequency neurotomy on a long-term basis in managing chronic thoracic pain

A comparative systematic review and meta-analysis of 3 routes of administration of epidural injections in lumbar disc herniation

BACKGROUND: The Best Practices in Pain Management from the U.S. Department of Health and Human Services (HHS) describes interventional techniques as part of a continuum. Epidural injections are commonly utilized modalities in managing low back and lower extremity pain. Epidural injections were initially administered in 1901 where the first descriptions of caudal epidural with local anesthetic for low back pain appeared. Since then, multiple developments have occurred. Currently, epidural injections are provided by caudal, interlaminar, and transforaminal approaches. The comparative effectiveness of each modality has been studied. However, comparative assessment has been sparse. OBJECTIVES: To assess the efficacy of 3 routes of administration of epidural injections for lumbar disc herniation. STUDY DESIGN: A systematic review and meta-analysis of randomized controlled trials (RCTs) of transforaminal, interlaminar and caudal epidural injections in managing chronic low back and lower extremity pain due to lumbar disc herniation. METHODS: RCTs with a placebo control or an active control design, performed under fluoroscopic guidance, with at least 6 months of follow-up are included. The outcome measures were pain relief and functional status improvement. Significant improvement was defined as 50% or greater pain relief and functional status improvement. Data extraction and methodological quality assessment were performed. Evidence was summarized utilizing principles of best evidence synthesis. RESULTS: A total of 21 trials were included. Of these, 7 studied caudal epidural injections, whereas transforaminal epidural injections were studied in 12 trials, and lumbar interlaminar epidural injections were studied in 10 trials, which all met inclusion criteria. Based on qualitative and quantitative analysis, which included conventional dual-arm and single-arm analysis for interlaminar epidural injections, and single-arm analysis for caudal and transforaminal epidural injections, and the approach to the epidural space, there is Level I evidence for local anesthetic and steroids, Level II for local anesthetic alone for transforaminal and interlaminar approaches, and Level II for the caudal approach with steroids or local anesthetic alone for short- and long-term relief. LIMITATIONS: There is a paucity of literature with intermediate or long-term relief of at least 6 months with appropriate outcome parameters. Conventional dual-arm meta-analysis was feasible only for interlaminar epidural injections. CONCLUSION: Epidural injections with local anesthetic and steroids showed Level I evidence for transforaminal and interlaminar approaches, whereas with local anesthetic alone Level II evidence was demonstrated. In contrast, caudal epidural injections showed Level II evidence with local anesthetic with steroids or local anesthetic alone