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. KEY WORDS: Chronic low back pain, lumbar radiculopathy, lumbar disc herniation, sciatica, epidural injections, local anesthetic, steroids, caudal epidural injections, interlaminar epidural injections, transforaminal epidural injections

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 (< 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.

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. KEY WORDS: Chronic low back pain, lumbar radiculopathy, sciatica, epidural injections, local anesthetic, steroids, caudal epidural injections, interlaminar epidural injections, transforaminal epidural injections

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’s 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.

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. KEY WORDS: Chronic spinal pain, interventional techniques, epidural procedures, caudal epidural, lumbar interlaminar epidural, cervical interlaminar epidural, thoracic interlaminar epidural, lumbar transforaminal epidural, percutaneous adhesiolysis DISCLAIMER: These guidelines are based on the best available evidence and do not constitute inflexible treatment recommendations. Due to the changing body of evidence, this document is not intended to be a “standard of care.” There was no external funding in the preparation of this manuscript.