The effectiveness of intradiscal biologic treatments for discogenic low back pain: a systematic review.

BACKGROUND CONTEXT: There are limited treatments for discogenic low back pain. Intradiscal injections of biologic agents such as platelet-rich plasma (PRP) or stem cells (SC) are theorized to have regenerative properties and have gained increasing interest as a possible treatment, but the evidence supporting their use in clinical practice is not yet well-defined. PURPOSE: Determine the effectiveness of intradiscal biologics for treating discogenic low back pain. STUDY DESIGN: PRISMA-compliant systematic review. PATIENT SAMPLE: Patients with discogenic low back pain confirmed by provocation discography or clinical and imaging findings consistent with discogenic pain. OUTCOME MEASURES: The primary outcome was the proportion of individuals with ≥50% pain relief after intradiscal biologic injection at 6 months. Secondary outcomes included ≥2-point pain score reduction on NRS; patient satisfaction; functional improvement; decreased use of other health care, including analgesics and surgery; and structural disc changes on MRI. METHODS: Comprehensive literature search performed in 2018 and updated in 2020. Interventions included were biologic therapies including mesenchymal stem cells, platelet rich plasma, microfragmented fat, amniotic membrane-based injectates, and autologous conditioned serum. Any other treatment (sham or active) was considered for comparative studies. Studies were independently reviewed. RESULTS: The literature search yielded 3,063 results, 37 studies were identified for full-text review, and 12 met established inclusion criteria for review. The quality of evidence on effectiveness of intradiscal biologics was very low. A single randomized controlled trial evaluating platelet-rich plasma reported positive outcomes but had significant methodological flaws. A single trial that evaluated mesenchymal stem cells was negative. Success rates for platelet-rich plasma injectate in aggregate were 54.8% (95% Confidence Interval: 40%-70%). For mesenchymal stem cells, the aggregate success rate at six months was 53.5% (95% Confidence Interval: 38.6%-68.4%), though using worst-case analysis this decreased to 40.7% (95% Confidence Interval: 28.1%-53.2%). Similarly, ≥30% functional improvement was achieved in 74.3% (95% Confidence Interval: 59.8%-88.7%) at six months but using worst-case analysis, this decreased to 44.1% (95% Confidence Interval: 28.1%-53.2%). CONCLUSION: Limited observational data support the use of intradiscal biologic agents for the treatment of discogenic low back pain. According to the Grades of Recommendation, Assessment, Development and Evaluation System, the evidence supporting use of intradiscal mesenchymal stem cells and platelet-rich plasma is very low quality.

Do Corticosteroid Injections for the Treatment of Pain Influence the Efficacy of Adenovirus Vector-Based COVID-19 Vaccines?

MYTH: Corticosteroid injection for the treatment of pain is known to decrease the efficacy of the adenovirus vector-based vaccines for COVID-19. FACT: There is currently no direct evidence to suggest that a corticosteroid injection before or after the administration of an adenovirus vector-based COVID-19 vaccine decreases the efficacy of the vaccine. However, based on the known timeline of hypothalamic-pituitary-adrenal axis suppression following epidural and intraarticular corticosteroid injections, and the timeline of the reported peak efficacy of the Janssen and AstraZeneca vaccines, physicians should consider timing an elective corticosteroid injection such that it is administered no less than 2 weeks prior to and no less than 2 weeks following a COVID-19 adenovirus vector-based vaccine dose, whenever possible. We emphasize the importance of risk/benefit analysis and shared decision making in determining the timing of corticosteroid injections for pain indications in relation to receipt of a COVID-19 vaccine given that patient-specific factors will vary.

The Effectiveness of Intraosseous Basivertebral Nerve Radiofrequency Neurotomy for the Treatment of Chronic Low Back Pain in Patients with Modic Changes: A Systematic Review.

OBJECTIVE: Determine the effectiveness of intraosseous basivertebral nerve radiofrequency neurotomy for the treatment of chronic low back pain with type 1 or 2 Modic changes. DESIGN: Systematic review. POPULATION: Persons aged ≥18 years with chronic low back pain with type 1 or 2 Modic changes. INTERVENTION: Intraosseous basivertebral nerve radiofrequency neurotomy. COMPARISON: Sham, placebo procedure, active standard care treatment, or none. OUTCOMES: The primary outcome of interest was the proportion of individuals with ≥50% pain reduction. Secondary outcomes included ≥10-point improvement in function as measured by Oswestry Disability Index as well as ≥2-point reduction in pain score on the Visual Analog Scale or Numeric Rating Scale, and decreased use of pain medication. METHODS: Three reviewers independently assessed publications before May 15, 2020, in MEDLINE and Embase and the quality of evidence was evaluated using the Grades of Recommendation, Assessment, Development, and Evaluation framework. RESULTS: Of the 725 publications screened, seven publications with 321 participants were ultimately included. The reported 3-month success rate for ≥50% pain reduction ranged from 45% to 63%. Rates of functional improvement (≥10-point Oswestry Disability Index improvement threshold) ranged from 75% to 93%. For comparison to sham treatment, the relative risk of treatment success defined by ≥50% pain reduction and ≥10-point Oswestry Disability Index improvement was 1.25 (95% confidence interval [CI]: .88-1.77) and 1.38 (95% CI: 1.10-1.73), respectively. For comparison to continued standard care treatment the relative risk of treatment success defined by ≥50% pain reduction and ≥10-point Oswestry Disability Index improvement was 4.16 (95% CI: 2.12-8.14) and 2.32 (95% CI: 1.52-3.55), respectively. CONCLUSIONS: There is moderate-quality evidence that suggests this procedure is effective in reducing pain and disability in patients with chronic low back pain who are selected based on type 1 or 2 Modic changes, among other inclusion and exclusion criteria used in the published literature to date. Success of the procedure appears to be dependent on effective targeting of the BVN. Non-industry funded high-quality, large prospective studies are needed to confirm these findings.

Reopening Interventional Pain Practices during the Early Phase of the COVID-19 Global Pandemic.

OBJECTIVE: Examine how interventional pain physicians navigated the early phase of reopening practices during the coronavirus disease 2019 (COVID-19) pandemic. METHODS: In June/July 2020, Spine Intervention Society members were queried about practice demographics, perception of COVID-19 prevalence, financial impact, and implementation of new tools and procedures when re-opening practices. RESULTS: Of the 2,295 members approached, 195 (8%) completed the survey. A majority (71%) reported using risk stratification tools and changing scheduling patterns. Nearly 70% performed initial assessments via telehealth and 87% for follow-up encounters. More than 80% performed symptom/temperature checks upon in-person clinic/facility entrance, and 63% screened patients via phone. Most (58%) did not test patients for COVID-19 for office visits, while 38% tested only if symptomatic. For epidural injections, intra-articular injections, and radiofrequency neurotomy procedures, 43% reported not testing patients, while 36% tested patients only if symptomatic. Most (70%) required patients to wear a mask upon entering the clinic/facility. For nonprocedure encounters, respondents used surgical masks (85%), gloves (35%), face shields/goggles (24%), N95 respirators (15%), and gowns (6%). Some (66%) discussed unique COVID-19 risks/complications and 26% provided written information. Most did not make changes to steroid dosage (67%) or peri-procedural anticoagulation management (97%). The vast majority (81%) estimated that COVID-19 will have a moderate-severe financial impact on their practice. CONCLUSIONS: COVID-19 has dramatically affected interventional pain practices with regard to telehealth, in-clinic precautions, screening/testing protocols, and patient counseling. Practice patterns will continue to evolve as we learn more about the disease and improve methods to provide safe and effective care.

The Effectiveness of Dorsal Root Ganglion Neurostimulation for the Treatment of Chronic Pelvic Pain and Chronic Neuropathic Pain of the Lower Extremity: A Comprehensive Review of the Published Data.

OBJECTIVE: To evaluate the effectiveness of dorsal root ganglion neurostimulation for the treatment of refractory, focal pain in the pelvis and lower extremities. DESIGN: Systematic review. OUTCOME MEASURES: The primary outcome was ≥50% pain relief. Secondary outcomes were physical function, mood, quality of life, opioid usage, and complications. RESULTS: One pragmatic randomized controlled trial, four prospective cohort studies, and eight case series met the inclusion criteria. A worst-case scenario analysis from the randomized controlled trial reported ≥50% pain relief in 74% of patients with dorsal root ganglion neurostimulation vs. 51% of patients who experienced at least 50% relief with spinal cord stimulation at 3 months. Cohort data success rates ranged from 43% to 83% at ≤6 months and 27% to 100% at >6 months. Significant improvements were also reported in the secondary outcomes assessed, including mood, quality of life, opioid usage, and health care utilization, though a lack of available quantitative data limits further statistical analysis. Complication rates vary, though the only randomized controlled trial reported a higher rate of adverse events than that seen with traditional neurostimulation. CONCLUSIONS: In accordance with the Grades of Recommendation, Assessment, Development, and Evaluation system, low-quality evidence supports dorsal root ganglion neurostimulation as a more effective treatment than traditional neurostimulation for pain and dysfunction associated with complex regional pain syndrome or causalgia. Very low-quality evidence supports dorsal root ganglion neurostimulation for the treatment of chronic pelvic pain, chronic neuropathic groin pain, phantom limb pain, chronic neuropathic pain of the trunk and/or limbs, and diabetic neuropathy.

The Effectiveness of Cervical Medial Branch Thermal Radiofrequency Neurotomy Stratified by Selection Criteria: A Systematic Review of the Literature.

OBJECTIVE: To determine the effectiveness of cervical medial branch thermal radiofrequency neurotomy in the treatment of neck pain or cervicogenic headache based on different selection criteria. DESIGN: Comprehensive systematic review. METHODS: A comprehensive literature search was conducted, and the authors screened and evaluated the studies. The Grades of Recommendation, Assessment, Development, and Evaluation system was used to assess all eligible studies. OUTCOME MEASURES: The primary outcome measure assessed was the success rate of the procedure, defined by varying degrees of pain relief following neurotomy. Data are stratified by number of diagnostic blocks and degree of pain relief. RESULTS: Results varied by selection criteria, which included triple placebo-controlled medial branch blocks, dual comparative medial branch blocks, single medial branch blocks, intra-articular blocks, physical examination findings, and symptoms alone. Outcome data showed a greater degree of pain relief more often when patients were selected by triple placebo-controlled medial branch blocks or dual comparative medial branch blocks, producing 100% relief of the index pain. The degree of pain relief was similar when triple or dual comparative blocks were used. CONCLUSIONS: Higher degrees of relief from cervical medial branch thermal radiofrequency neurotomy are more often achieved, to a statistically significant extent, if patients are selected on the basis of complete relief of index pain following comparative diagnostic blocks. If selected based on lesser degrees of relief, patients are less likely to obtain complete relief.

The Effectiveness of Lumbar Transforaminal Injection of Steroid for the Treatment of Radicular Pain: A Comprehensive Review of the Published Data.

OBJECTIVE: To determine the effectiveness of lumbar transforaminal injection of steroid for the treatment of radicular pain. DESIGN: Comprehensive systematic review. OUTCOME MEASURES: The primary outcome of interest was the proportion of individuals with reduction of pain by ≥50%. Additional outcomes of interest were a more-than-two-point reduction in pain score, patient satisfaction, functional improvement, decreased use of pain medication, and avoidance of spinal surgery. RESULTS: For patients with disc herniations, using the criterion of ≥50% reduction in pain, success rates across included studies (range) were 63% (58-68%) at one month, 74% (68-80%) at three months, 64% (59-69%) at six months, and 64% (57-71%) at one year. For patients with lumbar spinal stenosis, success rates across included studies (range) were 49% (43-55%) at one month, 48% (35-61%) at three months, 43% (33-53%) at six months, and 59% (45-73%) at one year, but there was a lack of corroboration from appropriately controlled studies. CONCLUSIONS: There is strong evidence that lumbar transforaminal injection of steroids is an effective treatment for radicular pain due to disc herniation. There is a lack of high-quality evidence demonstrating their effectiveness for the treatment of radicular pain due to spinal stenosis, though small studies suggest a possible benefit. Lumbar transforaminal injection of nonparticulate steroids is as effective as injections with particulate steroids.

Guidelines for Composing and Assessing a Paper on the Treatment of Pain: A Practical Application of Evidence-Based Medicine Principles to the Mint Randomized Clinical Trials.

Objective: To perform a thorough assessment of the recently published Mint Trials in order to illustrate how to read and analyze a study critically, according to principles of evidence-based medicine. Design: Narrative review. Method: We have applied the recently published guidelines for composing and assessing studies on the treatment of pain to a recently published article describing a large study that claimed its "findings do not support the use of radiofrequency denervation to treat chronic low back pain." These guidelines describe the critical components of a high-quality manuscript that allows communication of all relevant information from authors to readers. Results: Application of evidence-based medicine principles to the publication describing the Mint Trials reveals significant issues with the methodology and conclusions drawn by the authors. A thorough assessment demonstrates issues with inclusion/exclusion criteria, diagnostic block protocols, radiofrequency neurotomy technique, co-interventions, outcome measurement, power analysis, study sample characteristics, data analysis, and loss to follow-up. A failure to definitively establish a diagnosis, combined with use of an inadequate technique for radiofrequency neurotomy and numerous other methodological flaws, leaves the reader unable to draw meaningful conclusions from the study data. Conclusions: Critical analysis, rooted in principles of evidence-based medicine, must be employed by writers and readers alike in order to encourage transparency and ensure that appropriate conclusions are drawn from study data.

Risks and Benefits of Ceasing or Continuing Anticoagulant Medication for Image-Guided Procedures for Spine Pain: A Systematic Review.

Objective: To determine the risks of continuing or ceasing anticoagulant or antiplatelet medications prior to image-guided procedures for spine pain. Design: Systematic review of the literature with comprehensive analysis of the published data. Interventions: Following a search of the literature for studies pertaining to spine pain interventions in patients on anticoagulant medication, seven reviewers appraised the studies identified and assessed the quality of evidence presented. Outcome Measures: Evidence was sought regarding risks associated with either continuing or ceasing anticoagulant and antiplatelet medication in patients having image-guided interventional spine procedures. The evidence was evaluated in accordance with the Grades of Recommendation, Assessment, Development, and Evaluation system. Results: From a source of 120 potentially relevant articles, 14 provided applicable evidence. Procedures involving interlaminar access carry a nonzero risk of hemorrhagic complications, regardless of whether anticoagulants are ceased or continued. For other procedures, hemorrhagic complications have not been reported, and case series indicate that they are safe when performed in patients who continue anticoagulants. Three articles reported the adverse effects of ceasing anticoagulants, with serious consequences, including death. Conclusions: Other than for interlaminar procedures, the evidence does not support the view that anticoagulant and antiplatelet medication must be ceased before image-guided spine pain procedures. Meanwhile, the evidence shows that ceasing anticoagulants carries a risk of serious consequences, including death. Guidelines on the use of anticoagulants should reflect these opposing bodies of evidence.

Appropriate Use Criteria for Fluoroscopically Guided Diagnostic and Therapeutic Sacroiliac Interventions: Results from the Spine Intervention Society Convened Multispecialty Collaborative.

OBJECTIVE: To provide an overview of a multisociety effort to formulate appropriate use criteria for image-guided injections and radiofrequency procedures in the diagnosis and treatment of sacroiliac joint and posterior sacroiliac complex pain. METHODS: The Spine Intervention Society convened a multisociety effort to guide physicians and define for payers the appropriate use of image-guided injections and radiofrequency procedures. An evidence panel was established to write systematic reviews, define key terms and assumptions, and develop clinical scenarios to be addressed. The rating panel considered the evidence presented in the systematic reviews, carefully reviewed the definitions and assumptions, and rated the clinical scenarios. Final median ratings, in combination with the level of agreement, determined the final ratings for the appropriate use of sacroiliac injections and radiofrequency neurotomy. RESULTS: More than 10,000 scenarios were addressed in the appropriate use criteria and are housed within five modules in the portal, available on the Spine Intervention Society website: Module 1: Clinical Indications and Imaging; Module 2: Anticoagulants; Module 3: Timing of Injections; Module 4: Number of Injections; and Module 5: Lateral Branch Radiofrequency Neurotomy. Within several of these modules, several issues of interest are identified and discussed. CONCLUSIONS: Physicians and payers can access the appropriate use criteria portal on the Spine Intervention Society's website and select specific clinical indications for a particular patient in order to learn more about the appropriateness of the intervention(s) under consideration.

The Effectiveness and Risks of Fluoroscopically Guided Lumbar Interlaminar Epidural Steroid Injections: A Systematic Review with Comprehensive Analysis of the Published Data.

Objective: To determine the effectiveness and risks of fluoroscopically guided lumbar interlaminar epidural steroid injections. Design: Systematic review of the literature with comprehensive analysis of the published data. Interventions: Three reviewers with formal training in evidence-based medicine searched the literature on fluoroscopically guided lumbar interlaminar epidural steroid injections. A larger team consisting of five reviewers independently assessed the methodology of studies found and appraised the quality of the evidence presented. Outcome Measures: The primary outcome assessed was pain relief. Other outcomes such as functional improvement, reduction in surgery rate, decreased use of opioids/medications, and complications were noted, if reported. The evidence on each outcome was appraised in accordance with the Grades of Recommendation, Assessment, Development and Evaluation (GRADE) system of evaluating evidence. Results: The search yielded 71 primary publications addressing fluoroscopically guided lumbar interlaminar epidural steroid injections. There were no explanatory studies and all pragmatic studies identified were of low quality, yielding evidence comparable to observational studies. Conclusions: The body of evidence regarding effectiveness of fluoroscopically guided interlaminar epidural steroid injection is of low quality according to GRADE. Studies suggest a lack of effectiveness of fluoroscopically guided lumbar interlaminar epidural steroid injections in treating primarily axial pain regardless of etiology. Most studies on radicular pain due to lumbar disc herniation and stenosis do, however, report statistically significant short-term improvement in pain.

The Effectiveness and Risks of Non-Image-Guided Lumbar Interlaminar Epidural Steroid Injections: A Systematic Review with Comprehensive Analysis of the Published Data.

OBJECTIVE: To determine the effectiveness and risks of non-image-guided lumbar interlaminar epidural steroid injections. DESIGN: Systematic review. INTERVENTIONS: Three reviewers with formal training and certification in evidence-based medicine searched the literature on non-image-guided lumbar interlaminar epidural steroid injections. A larger team of seven reviewers independently assessed the methodology of studies found and appraised the quality of the evidence presented. OUTCOME MEASURES: The primary outcome assessed was pain relief. Other outcomes such as functional improvement, reduction in surgery rate, decreased use of opioids, and complications were noted, if reported. The evidence was appraised in accordance with the Grades of Recommendation, Assessment, Development and Evaluation (GRADE) system of evaluating evidence. RESULTS: The searches yielded 92 primary publications addressing non-image-guided lumbar interlaminar epidural steroid injections. The evidence supporting the effectiveness of these injections for pain relief and functional improvement in patients with lumbar radicular pain due to disc herniation or neurogenic claudication secondary to lumbar spinal stenosis is limited. This procedure may provide short-term benefit in the first 3-6 weeks. The small number of case reports on significant risks suggests these injections are relatively safe. In accordance with GRADE, the quality of evidence is very low. CONCLUSIONS: In patients with lumbar radicular pain secondary to disc herniation or neurogenic claudication due to spinal stenosis, non-image-guided lumbar interlaminar epidural steroid injections appear to have clinical effectiveness limited to short-term pain relief. Therefore, in a contemporary medical practice, these procedures should be restricted to the rare settings where fluoroscopy is not available.

Fluoroscopically Guided Diagnostic and Therapeutic Intra-Articular Sacroiliac Joint Injections: A Systematic Review.

OBJECTIVE: To assess the validity of fluoroscopically guided diagnostic intra-articular injections of local anesthetic and effectiveness of intra-articular steroid injections in treating sacroiliac joint (SIJ) pain. DESIGN: Systematic review. INTERVENTIONS: Ten reviewers independently assessed 45 publications on diagnostic validity or effectiveness of fluoroscopically guided intra-articular SIJ injections. OUTCOME MEASURES: For diagnostic injections, the primary outcome was validity; for therapeutic injections, analgesia. Secondary outcomes were also described. RESULTS: Of 45 articles reviewed, 39 yielded diagnostic data on physical exam findings, provocation tests, and SIJ injections for diagnosing SIJ pain, and 15 addressed therapeutic effectiveness. When confirmed by comparative local anesthetic blocks with a high degree of pain relief, no single physical exam maneuver predicts response to diagnostic injections. When at least three physical exam findings are present, sensitivity, and specificity increases significantly. The prevalence of SIJ pain is likely 20-30% among patients that have suspected SIJ pain based on history and physical examination. This estimate may be higher in certain subgroups such as the elderly and fusion patients. Two randomized controlled trials and multiple observational studies supported the effectiveness of therapeutic sacroiliac joint injections. CONCLUSIONS: Based on this literature, it is unclear whether image-guided intra-articular diagnostic injections of local anesthetic predict positive responses to therapeutic agents. The overall quality of evidence is moderate for the effectiveness of therapeutic SIJ injections.