Effectiveness of Facet Joint Nerve Blocks in Managing Chronic Axial Spinal Pain of Facet Joint Origin: A Systematic Review and Meta-Analysis.

BACKGROUND: Chronic axial spinal pain is one of the major causes of disability. Literature shows that spending on low back and neck pain and musculoskeletal disorders continues to escalate, not only with disability, but also with increasing costs, accounting for the highest amount of various disease categories. Based on the current literature utilizing controlled diagnostic blocks, facet joints, nerve root dura, and sacroiliac joints have been shown as potential sources of spinal pain. Therapeutic facet joint interventional modalities of axial spinal pain include radiofrequency neurotomy, therapeutic facet joint nerve blocks, and therapeutic intraarticular injections. OBJECTIVE: The objective of this systematic review and meta-analysis is to evaluate the effectiveness of facet joint nerve blocks as a therapeutic modality in managing chronic axial spinal pain of facet joint origin. STUDY DESIGN: A systematic review and meta-analysis of randomized controlled trials (RCTs) and observational studies utilizing the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist. METHODS: The available literature on facet joint nerve blocks in axial spinal pain 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 evidence was graded according to Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) assessment criteria. The level of evidence was based on best evidence synthesis with modified grading of qualitative evidence from Level I to Level V. A comprehensive literature search of multiple databases from 1966 to July 2023, including manual searches of the bibliography of known review articles was performed. Quality assessment of the included studies and best evidence synthesis were incorporated into qualitative and quantitative evidence synthesis. OUTCOME MEASURES: The primary outcome measure was the proportion of patients with significant relief and functional improvement of greater than 50% of at least 3 months. Duration of relief was categorized as short-term (less than 6 months) and long-term (greater than 6 months). RESULTS: This assessment identified 8 high-quality and one moderate quality RCTs and 8 high quality and 4 moderate quality non-randomized studies with application of spinal facet joint nerve blocks as therapeutic modalities. However, based on the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) assessment, only 3 of the 21 studies showed high levels of evidence and clinical applicability, with 11 studies showing moderate levels of GRADE evidence and clinical applicability. LIMITATIONS: Despite the availability of multiple studies, the paucity of literature is considered as the major drawback. Based on Grading of Recommendations, Assessment Development, and Evaluations (GRADE) assessment, only 3 of the 21 studies showed high levels of evidence and clinical applicability. CONCLUSION: Based on the present systematic review and meta-analysis with 9 RCTs and 12 non-randomized studies, the evidence is Level II with moderate to strong recommendation for therapeutic facet joint nerve blocks in managing spinal facet joint pain.

The impact of scrambler therapy on pain and quality of life for chemotherapy-induced peripheral neuropathy: A pilot study.

BACKGROUND: Chemotherapy-induced peripheral neuropathy (CIPN) is a debilitating disturbance among patients who received chemotherapy, with no effective treatment available. Scrambler therapy (ST) is a noninvasive treatment capable of improving multiple quality-of-life symptoms beyond pain. We aimed to evaluate the efficacy of ST for pain and nonpain symptoms related to CIPN. METHODS: Ten patients with moderate to severe CIPN symptoms for >3 months were enrolled in a single-arm trial of ST for 10 daily sessions. CIPN-related symptoms were measured throughout the treatment period and up to 6 months thereafter. RESULTS: The worst pain was reduced by 6 months (p = 0.0039). QST demonstrated the greatest improvement in pressure of 60 g (p = 0.308, Cohen's d = 0.42) and cold temperature threshold of 2.5°C (p = 0.9375, Cohen's d = 0.51) in the gastrocnemius area. Symptoms of numbness, tingling, trouble walking, and disturbed sleep had significant improvements at 6 months. Pain medication use decreased by 70% at the end of treatment and by 42% at 6 months. Patient satisfaction was high (82%) and no adverse events with ST treatment were reported. CONCLUSIONS: The results of this pilot trial support the use of ST by demonstrating improvement in multiple domains of quality of life for CIPN patients during an extended follow-up of 6 months. However, further large-scale studies are needed to confirm our findings.

Bardoxolone Methyl Ameliorates Chemotherapy-Induced Neuropathic Pain by Activation of Phosphorylated Nuclear Factor Erythroid 2-Related Factor 2 in the Dorsal Root Ganglia.

BACKGROUND: Many chemotherapeutic drugs, including paclitaxel, produce neuropathic pain in patients with cancer, which is a dose-dependent adverse effect. Such chemotherapy-induced neuropathic pain (CINP) is difficult to treat with existing drugs. Nuclear factor erythroid 2-related factor 2 (Nrf2) is a major regulator of antioxidative responses and activates phosphorylated Nrf2 (pNrf2). We determined the analgesic effects of bardoxolone methyl (BM), an Nrf2 activator, and the role of pNrf2 on CINP. METHODS: CINP was induced in rats by intraperitoneally injecting paclitaxel on 4 alternate days in rats. BM was injected systemically as single or repeated injections after pain fully developed. RNA transcriptome, mechanical hyperalgesia, levels of inflammatory mediators and pNrf2, and location of pNrf2 in the dorsal root ganglia (DRG) were measured by RNA sequencing, von Frey filaments, Western blotting, and immunohistochemistry in rats and human DRG samples. In addition, the mitochondrial functions in 50B11 DRG neuronal cells were measured by fluorescence assay. RESULTS: Our RNA transcriptome of CINP rats showed a downregulated Nrf2 pathway in the pain condition. Importantly, single and repeated systemic injections of BM ameliorated CINP. Paclitaxel increased inflammatory mediators, but BM decreased them and increased pNrf2 in the DRG. In addition, paclitaxel decreased mitochondrial membrane potential and increased mitochondrial volume in 50B11 cells, but BM restored them. Furthermore, pNrf2 was expressed in neurons and satellite cells in rat and human DRG. CONCLUSIONS: Our results demonstrate the analgesic effects of BM by Nrf2 activation and the fundamental role of pNrf2 on CINP, suggesting a target for CINP and a therapeutic strategy for patients.

Nurse-Administered Auricular Point Acupressure for Cancer-Related Pain.

PURPOSE: The study aimed to (1) examine the feasibility of providing a training course on auricular point acupressure (APA) for clinical oncology nurses to integrate APA into real-world nursing care settings, and (2) examine the effectiveness of APA on cancer-related pain (CRP) under usual inpatient oncology ward conditions. METHODS: This was a 2-phase feasibility study. Phase 1, an in-person, 8 hour training program was provided to oncology nurses. Phase 2, a prospective and feasibility study was conducted to evaluate the integration of APA into nursing care activities to manage CRP. Oncology patients were included if their pain was rated at ≥4 on a 0 to 10 numeric rating scale in the past 24 hours. Patients received 1 APA treatment administered by the nurses and were instructed to stimulate the points for 3 days. Study outcomes (pain intensity, fatigue, and sleep disturbance), pain medication use, and APA practice were measured by a phone survey daily. RESULTS: Ten oncology nurses received APA training in phase 1. APA had been added to the hospital's electronic health records (EHRs) as a pain treatment. In phase 2, 33 oncology patients received APA treatment with a 100% adherence rate (pressing the seeds 3 times per day, 3 minutes per time based on the suggestion). The side effects of APA were minimal (~8%-12% felt tenderness on the ear). After 3 days of APA, patients reported 38% pain relief, 39% less fatigue, and 45% improvement in sleep disturbance; 24% reduced any type of pain medication use and 19% reduced opioid use (10 mg opioids using milligram morphine equivalent). The major barrier to integrating APA into routine nursing practice was time management (how to include APA in a daily workflow). CONCLUSION: It is feasible to provide 8-hour training to oncology nurses for mastering APA skill and then integrating APA into their daily nursing care for patients with CRP. Based on the promising findings (decreased pain, improved fatigue and sleep disturbance, and less opioid use), the next step is to conduct a randomized clinical trial with a larger sample to confirm the efficacy of APA for oncology nurses to treat CRP in real-world practice.ClinicalTrial.gov identifier number: NCT04040140.

The Influence of COVID-19 on Utilization of Epidural Procedures in Managing Chronic Spinal Pain in the Medicare Population.

STUDY DESIGN: A retrospective cohort study of utilization patterns and variables of epidural injections in the fee-for-service (FFS) Medicare population. OBJECTIVES: To update the utilization of epidural injections in managing chronic pain in the FFS Medicare population, from 2000 to 2020, and assess the impact of COVID-19. SUMMARY OF BACKGROUND DATA: The analysis of the utilization of interventional techniques also showed an annual decrease of 2.5% per 100,000 FFS Medicare enrollees from 2009 to 2018, contrasting to an annual increase of 7.3% from 2000 to 2009. The impact of the COVID-19 pandemic has not been assessed. METHODS: This analysis was performed by utilizing master data from the Centers for Medicare and Medicaid Services, physician/supplier procedure summary from 2000 to 2020. The analysis was performed by the assessment of utilization patterns using guidance from Strengthening the Reporting of Observational Studies in Epidemiology. RESULTS: Epidural procedures declined at a rate of 19% per 100,000 Medicare enrollees in the FFS Medicare population in the United States from 2019 to 2020, with an annual decline of 3% from 2010 to 2019. From 2000 to 2010, there was an annual increase of 8.3%. This analysis showed a decline in all categories of epidural procedures from 2019 to 2020. The major impact of COVID-19, with closures taking effect from April 1, 2020, through December 31, 2020, will be steeper and rather dramatic compared with April 1 to December 31, 2019. However, monthly data from the Centers for Medicare and Medicaid Services is not available as of now. Overall declines from 2010 to 2019 showed a decrease for cervical and thoracic transforaminal injections with an annual decrease of 5.6%, followed by lumbar interlaminar and caudal epidural injections of 4.9%, followed by 1.8% for lumbar/sacral transforaminal epidurals, and 0.9% for cervical and thoracic interlaminar epidurals. CONCLUSION: Declining utilization of epidural injections in all categories was exacerbated to a decrease of 19% from 2019 to 2020, related, in part, to the COVID-19 pandemic. This followed declining patterns of epidural procedures of 3% overall annually from 2010 to 2019.

A Systematic Review and Meta-analysis of the Effectiveness of Radiofrequency Neurotomy in Managing Chronic Neck Pain.

BACKGROUND: Extensive research into potential sources of neck pain and referred pain into the upper extremities and head has shown that the cervical facet joints can be a potential pain source confirmed by precision, diagnostic blocks. STUDY DESIGN: Systematic review and meta-analysis utilizing the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist, quality assessment of the included studies, conventional and single-arm meta-analysis, and best evidence synthesis. OBJECTIVE: The objective of this systematic review and meta-analysis is to evaluate the effectiveness of radiofrequency neurotomy as a therapeutic cervical facet joint intervention in managing chronic neck pain. METHODS: Available literature was included. Methodologic quality assessment of studies was performed from 1996 to September 2021. The level of evidence of effectiveness was determined. RESULTS: Based on the qualitative and quantitative analysis with single-arm meta-analysis and Grading of Recommendations, Assessment, Development and Evaluations (GRADE) system of appraisal, with inclusion of one randomized controlled trial (RCT) of 12 patients in the treatment group and eight positive observational studies with inclusion of 589 patients showing positive outcomes with moderate to high clinical applicability, the evidence is level II in managing neck pain with cervical radiofrequency neurotomy. The evidence for managing cervicogenic headache was level III to IV with qualitative analysis and single-arm meta-analysis and GRADE system of appraisal, with the inclusion of 15 patients in the treatment group in a positive RCT and 134 patients in observational studies. An overwhelming majority of the studies produced multiple lesions. LIMITATIONS: There was a paucity of literature and heterogeneity among the available studies. CONCLUSION: This systematic review and meta-analysis shows level II evidence with radiofrequency neurotomy on a long-term basis in managing chronic neck pain with level III to IV evidence in managing cervicogenic headaches.

A Systematic Review and Meta-analysis of the Effectiveness of Radiofrequency Neurotomy in Managing Chronic Neck Pain.

Background: Extensive research into potential sources of neck pain and referred pain into the upper extremities and head has shown that the cervical facet joints can be a potential pain source confirmed by precision, diagnostic blocks. Study Design: Systematic review and meta-analysis utilizing the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist, quality assessment of the included studies, conventional and single-arm meta-analysis, and best evidence synthesis. Objective: The objective of this systematic review and meta-analysis is to evaluate the effectiveness of radiofrequency neurotomy as a therapeutic cervical facet joint intervention in managing chronic neck pain. Methods: Available literature was included. Methodologic quality assessment of studies was performed from 1996 to September 2021. The level of evidence of effectiveness was determined. Results: Based on the qualitative and quantitative analysis with single-arm meta-analysis and Grading of Recommendations, Assessment, Development and Evaluations (GRADE) system of appraisal, with inclusion of one randomized controlled trial (RCT) of 12 patients in the treatment group and eight positive observational studies with inclusion of 589 patients showing positive outcomes with moderate to high clinical applicability, the evidence is level II in managing neck pain with cervical radiofrequency neurotomy. The evidence for managing cervicogenic headache was level III to IV with qualitative analysis and single-arm meta-analysis and GRADE system of appraisal, with the inclusion of 15 patients in the treatment group in a positive RCT and 134 patients in observational studies. An overwhelming majority of the studies produced multiple lesions. Limitations: There was a paucity of literature and heterogeneity among the available studies. Conclusion: This systematic review and meta-analysis shows level II evidence with radiofrequency neurotomy on a long-term basis in managing chronic neck pain with level III to IV evidence in managing cervicogenic headaches. Supplementary Information: The online version contains supplementary material available at 10.1007/s40122-022-00455-0.

Comparative Systematic Review and Meta-Analysis of Cochrane Review of Epidural Injections for Lumbar Radiculopathy or Sciatica.

BACKGROUND: Epidural injections are among the most commonly performed procedures for managing low back and lower extremity pain. Pinto et al and Chou et al previously performed systematic reviews and meta-analyses, which, along with a recent update from Oliveira et al showing the lack of effectiveness of epidural steroid injections in managing lumbar disc herniation, spinal stenosis, and radiculopathy. In contrast to these papers, multiple other systematic reviews and meta-analyses have supported the effectiveness and use of epidural injections utilizing fluoroscopically guided techniques. A major flaw in the review can be related to attributing active-controlled trials to placebo-controlled trials. The assumption that local anesthetics do not provide sustained benefit, despite extensive evidence that local anesthetics provide long-term relief, similar to a combination of local anesthetic with steroids is flawed. STUDY DESIGN: The Cochrane Review of randomized controlled trials (RCTs) of epidural injections in managing chronic low back and lower extremity pain with sciatica or lumbar radiculopathy were reanalyzed using systematic methodology and meta-analysis. OBJECTIVES: To re-evaluate Cochrane data on RCTs of epidural injections in managing chronic low back and lower extremity pain with sciatica or lumbar radiculopathy utilizing qualitative and quantitative techniques with dual-arm and single-arm analysis. METHODS: In this systematic review, we have used the same RCTs from the Cochrane Review of a minimum of 20% change in pain scale or significant pain relief of >= 50%. The outcome measures were pain relief and functional status improvement. Significant improvement was defined as 50% or greater pain relief and functional status improvement. Our review was performed utilizing the Cochrane Review methodologic quality assessment and the Interventional Pain Management Techniques - Quality Appraisal of Reliability and Risk of Bias Assessment (IPM-QRB). Evidence was summarized utilizing the principles of best evidence synthesis and the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) system. Clinical relevance of the pragmatic nature of each study was assessed. RESULTS: In evaluating the RCTs in the Cochrane Review, 10 trials were performed with fluoroscopic guidance. Utilizing conventional dual-arm and single-arm meta-analysis, the evidence is vastly different from the interpretation of the data within the Cochrane Review. The overall combined evidence is Level I, or strong evidence, at one and 3 months, and Level II, or moderate evidence, at 6 and 12 months. LIMITATIONS: The limitation of this study is that only data contained in the Cochrane Review were analyzed. CONCLUSION: A comparative systematic review and meta-analysis of the Cochrane Review of randomized controlled trials (RCTs) of epidural injections in managing chronic low back and lower extremity pain with sciatica or lumbar radiculopathy yielded different results. This review, based on the evidence derived from placebo-controlled trials and active-controlled trials showed Level I, or strong evidence, at one and 3 months and Level II at 6 and 12 months. This review once again emphasizes the importance of the allocation of studies to placebo-control and active-control groups, utilizing standards of practice with inclusion of only the studies performed under fluoroscopic guidance.

Current Understanding of Phantom Pain and its Treatment.

BACKGROUND: Phantom limb pain (PLP), defined as a painful sensation in a portion of the body that has been amputated, occurs in upwards of 80% of limb amputees and can significantly impact a patient's quality of life. First hypothesized in 1551, the disease has been poorly understood for much of this time. Still today, the exact etiology of the condition is yet to be elucidated. In the periphery, PLP resembles the neuronal changes seen in other neuropathic pain conditions. However, in the central nervous system (CNS), imaging studies suggest changes unique to PLP, such as cortical reorganization. Despite a growing understanding of its underpinnings, a mechanism-based treatment is not yet available. Rather, a plethora of treatment methodologies are available with varying levels of supporting evidence and many treatments being utilized based on efficacy seen in non-PLP patients. OBJECTIVES: In this review, we provide a thorough summary of the current literature regarding PLP's etiology, diagnosis, treatment, and attempts to prevent the development of PLP following amputation. STUDY DESIGN: A narrative review. METHODS: This was a narrative review conducted after an extensive and thorough review of available literature on the topic from a variety of sources. RESULTS: Current evidence supports a central reorganization process with potential amplification of aberrant peripheral inputs as the etiology of PLP. This conclusion is supported by functional neuroimaging as well as the failure of peripherally focused treatments. Treatment of PLP remains difficult due to varying response rates to therapies. Nonetheless, there are several treatment modalities that have proven effective in the majority of patients tested, ranging from noninvasive systemic pharmacotherapy to more invasive neuromodulation, such as spinal cord stimulation. While opioid therapy remains the most evidence-based treatment, the newer neuromodulation techniques appear to be superior in symptom reduction with minimal side effects. LIMITATIONS: Evidence for the treatment of PLP is largely restricted to uncontrolled case reports and/or small single-site uncontrolled case series. Some research is further hampered by the presence of confounding factors such as concurrent treatment regimens. CONCLUSIONS: While PLP remains a difficult-to-treat condition, practitioners can greatly improve the quality of life of patients suffering from the condition with a wide range of developing treatments. For pain intractable to traditional pharmacologic treatment, neuromodulation therapies have proven to be highly effective with minimal side effect profiles.

COVID-19 Pandemic Reduced Utilization Of Interventional Techniques 18.7% In Managing Chronic Pain In The Medicare Population In 2020: Analysis Of Utilization Data From 2000 To 2020.

BACKGROUND: Multiple publications have shown the significant impact of the COVID-19 pandemic on US healthcare and increasing costs over the recent years in managing low back and neck pain as well as other musculoskeletal disorders. The COVID-19 pandemic has affected many modalities of treatments, including those related to chronic pain management, including both interventional techniques and opioids. While there have not been assessments of utilization of interventional techniques specific to the ongoing COVID-19 pandemic, previous analysis published with data from 2000 to 2018 demonstrated a decline in utilization of interventional techniques from 2009 to 2018 of 6.7%, with an annual decline of 0.8% per 100,000 fee-for-service (FFS) in the Medicare population. During that same time, the Medicare population has grown by 3% annually. OBJECTIVES: The objectives of this analysis include an evaluation of the impact of the COVID-19 pandemic, as well as an updated assessment of the utilization of interventional techniques in managing chronic pain in the Medicare population from 2010 to 2019, 2010 to 2020, and 2019 to 2020 in the FFS Medicare population of the United States. STUDY DESIGN: Utilization patterns and variables of interventional techniques with the impact of the COVID-19 pandemic in managing chronic pain were assessed from 2000 to 2020 in the FFS Medicare population of the United States. METHODS: The data for the analysis was obtained from the master database from the Centers for Medicare & Medicaid Services (CMS) physician/supplier procedure summary from 2000 to 2020. RESULTS: The results of the present investigation revealed an 18.7% decrease in utilization of all interventional techniques per 100,000 Medicare beneficiaries from 2019 to 2020, with a 19% decrease for epidural and adhesiolysis procedures, a 17.5% decrease for facet joint interventions and sacroiliac joint blocks, and a 25.4% decrease for disc procedures and other types of nerve blocks. The results differed from 2000 to 2010 with an annualized increase of 10.2% per 100,000 Medicare population compared to an annualized decrease of 0.4% from 2010 to 2019, and a 2.5% decrease from 2010 to 2020 for all interventional techniques. For epidural and adhesiolysis procedures decreases were more significant and annualized at 3.1% from 2010 to 2019, increasing the decline to 4.8% from 2010 to 2020. For facet joint interventions and sacroiliac joint blocks, the reversal of growth patterns was observed but maintained at an annualized rate increase of 2.1% from 2010 to 2019, which changed to a decrease of 0.01% from 2010 to 2020. Disc procedures and other types of nerve blocks showed similar patterns as epidurals with an 0.8% annualized reduction from 2010 to 2019, which was further reduced to 3.6% from 2010 to 2020 due to COVID-19. LIMITATIONS: Data for the COVID-19 pandemic impact were available only for 2019 and 2020 and only the FFS Medicare population was utilized; utilization patterns in Medicare Advantage Plans, which constitutes almost 40% of the Medicare enrollment in 2020 were not available. Moreover, this analysis shares the limitations present in all retrospective reviews of claims based datasets. CONCLUSION: The decline driven by the COVID-19 pandemic was 18.7% from 2019 to 2020. Overall decline in utilization in interventional techniques from 2010 to 2020 was 22.0% per 100,000 Medicare population, with an annual diminution of 2.5%, despite an increase in the population rate of 3.3% annualized (38.9% overall) and Medicare enrollees of 33.4% and 2.9% annually.

Impact Of COVID-19 Pandemic and Updated Utilization Patterns of Sacroiliac Joint Injections from 2000 to 2020 in The Fee-For-Service (FFS) Medicare Population.

BACKGROUND: Among the multiple causes of low back and lower extremity pain, sacroiliac joint pain has shown to be prevalent in 10% to 25% of patients with persistent axial low back pain without disc herniation, discogenic pain, or radiculitis. Over the years, multiple Current Procedural Terminology (CPT) codes have evolved with the inclusion of intraarticular injections, nerve blocks, and radiofrequency neurotomy, in addition to percutaneous sacroiliac joint fusions. Previous assessments of utilization patterns of sacroiliac joint interventions only included sacroiliac joint intraarticular injections, since the data was not available prior to the introduction of new codes. A recent assessment revealed an increase of 11.3%, and an annual increase of 1.2% per 100,000 Medicare population from 2009 to 2018, showing a decline in growth patterns. During the past 2 years, the COVID-19 pandemic has also had significant effects on the utilization patterns of sacroiliac joint interventions. STUDY DESIGN: The impact of the COVID-19 pandemic and analysis of growth patterns of sacroiliac joint interventions (intraarticular injections, nerve blocks, radiofrequency neurotomy, arthrodesis and fusion) was evaluated from 2010 to 2019 and 2010 to 2020, with a comparative analysis from 2019 to 2020 to assess the impact of the COVID-19 pandemic. OBJECTIVES: To update utilization patterns of sacroiliac joint interventions with assessment of the impact of the COVID-19 pandemic. METHODS: The Centers for Medicare and Medicaid Services (CMS) Physician/Supplier Procedure Summary (PSPS) Master dataset was utilized in the present analysis. RESULTS: The results of this evaluation demonstrated a significant impact of the COVID-19 pandemic with a 19.2% decrease of utilization of sacroiliac joint intraarticular injections from 2019 to 2020. There was a 23.3% increase in sacroiliac joint arthrodesis and a 5.3% decrease for sacroiliac joint fusions with small numbers from 2019 to 2020. However, data was not available for sacroiliac joint nerve blocks and sacroiliac joint radiofrequency neurotomy as these codes were incorporated in 2020. Overall, from 2010 to 2019, sacroiliac joint intraarticular injections showed an annual increase of 0.9% per 100,000 Medicare population. Sacroiliac joint arthrodesis and fusion showed an annual increase from 2010 to 2020 per 100,000 Medicare population of 29% for arthrodesis and 13.3% for fusion. LIMITATIONS: Limitations of this study include a lack of inclusion of Medicare Advantage patients constituting approximately 30% to 40% of the overall Medicare population. As with all claims-based data analyses, this study is retrospective and thus potentially limited by bias. Finally, patients who are non-Medicare are not part of the dataset. CONCLUSIONS: The study shows the impact of the COVID-19 pandemic with a significant decrease of intraarticular injections of 19.2% from 2019 to 2020 per 100,000 Medicare population. These decreases of intraarticular injections are accompanied by a 5.3% decrease of fusion, but a 23.3% increase of arthrodesis from 2019 to 2020 per 100,000 Medicare population. Overall, the results showed an annual increase of 0.9% per 100,000 Medicare population for intraarticular injections, a 35.4% annual increase for sacroiliac joint arthrodesis and an increase of 15.5% for sacroiliac joint fusion from 2010 to 2019.

Scrambler therapy for noncancer neuropathic pain: a focused review.

PURPOSE OF REVIEW: Therapeutic methods for neuropathic are limited; available drugs can be inadequate or have adverse effects that compromise quality of life. Interest has grown in alternatives to pharmacologic therapy for neuropathic pain. We present a focused review of the literature about the relatively novel noninvasive, nonpharmacologic electrocutaneous nerve stimulation technique called scrambler therapy for treating noncancer neuropathic pain. RECENT FINDINGS: Neuromodulation techniques targeting peripheral sites have changed rapidly in recent years. Several clinical studies have demonstrated the analgesic effect of scrambler therapy after 10 sessions of treatment for various types of pain. Although scrambler therapy was originally used for cancer pain, its indications have broadened to postoperative pain, chemotherapy-induced peripheral neuropathy, postherpetic neuralgia, low back pain, diabetic neuropathy, complex regional pain syndrome and central pain syndrome. That said, some of the studies are controversial owing to their small sample size, lack of appropriate scrambler therapy protocol and possible lack of experience of the operators. SUMMARY: We present the historical perspective, mechanism of action and trial outcomes of scrambler therapy, representing an avenue for managing neuropathic pain without drugs. Well designed phase II/III clinical trials must be conducted to confirm the positive findings reported using scrambler therapy technology. If validated, scrambler therapy could be a game changer.

Catheter-based Techniques for Terminal Cancer Pain: A Review of Nonneuraxial Interventions with Clinical Implications for End-of-Life Pain Management.

BACKGROUND: Evidence suggests that a significant proportion of terminal cancer patients have uncontrolled or inadequately controlled pain when using the World Health Organization (WHO) analgesic ladder approach. The use of interventional techniques has proven to reduce pain that is refractory to conventional methods. However, despite the use of well-established techniques (e.g., intrathecal drug delivery, celiac plexus blocks, etc), nonneuraxial, catheter-based techniques remain underutilized. OBJECTIVE: The purpose of this narrative review is to examine the evidence for nonneuraxial, catheter-based techniques in treating terminal cancer pain, the barriers to implementation, and its role in bridging the gap between single shot techniques and surgically implanted devices. STUDY DESIGN: This is a narrative review article summarizing case reports, case series, retrospective studies, prospective studies, and review articles published at any time frame on the use of nonneuraxial, catheter-based techniques for the treatment of cancer pain in the end-of-life setting. SETTING: The University of Texas MD Anderson Cancer Center. METHODS: A literature search was conducted from November 2020 to January 2021 using the PubMed database and keywords related to nonneuraxial catheters, terminal cancer pain, and hospice. All English-based literature published at any time frame involving human patients was included. RESULTS: The number of studies referencing the use of nonneuraxial, catheter-based techniques for the treatment of terminal cancer pain is limited (n = 25). All of these studies were small, single-center, nonrandomized, noncontrolled case series and case reports. A total of 63 patients were evaluated across all studies, with the largest study involving 12 patients. The most common medication used was monotherapy with bupivacaine or ropivacaine and the longest duration of continuous catheter usage was 217 days. Of the studies that reported outcomes, the majority reported a reduction in pain. Very few studies reported catheter-related adverse events and tunneling appeared to be an important factor in reducing complications. LIMITATIONS: No studies were available comparing the use of nonneuraxial, catheter-based techniques to conventional systemic medical management. Further, the studies in this review were heterogenous and limited to a small sample sizes reported in case reports and case series only. CONCLUSION: Nonneuraxial, catheter-based techniques have the potential to play a significant role in the treatment of terminal cancer pain. Despite limited data, initial findings indicate that nonneuraxial, catheter-based techniques have the potential to bridge the gap between single shot interventions and surgical implanted devices by providing an effective, continuous therapy, with a lower risk profile.

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.

Calcium-independent phospholipase A2 inhibitor produces an analgesic effect in a rat model of neuropathic pain by reducing central sensitization in the dorsal horn.

OBJECTIVE: Phospholipase A2 (PLA2) plays an important role in regulating the production of arachidonic acid and various eicosanoids. The aim of our study was to investigate the analgesic mechanisms of calcium-dependent cytosolic phospholipase A2 and calcium-independent PLA2 (iPLA2) inhibitors in the spinal cord in a rat model of neuropathic pain. METHODS: Lumbar 5 spinal nerve ligation was performed in male Sprague-Dawley rats to develop a peripheral neuropathic pain model. Paw withdrawal thresholds in response to von Frey filaments, brush, pressure, and pinch were measured. Lumbar wide dynamic range neuronal firing rates and iPLA2 subtype expression were measured by in vivo extracellular recording and double immunofluorescence staining, respectively. RESULTS: In our rat models, oral administration of prednisolone, a non-selective PLA2 inhibitor, and intrathecal injection of bromoenolactone, a iPLA2 inhibitor, significantly increased the ipsilateral hindpaw withdrawal thresholds in response to von Frey filament stimulation, but intrathecal injection of arachidonyl trifluoromethyl ketone, a selective cytosolic PLA2 inhibitor, did not show significant changes. In spinal dorsal horn neurons, bromoenolactone reduced neuronal firing rates in response to withdrawal stimulation and spontaneous firing rates in the ipsilateral side of the spinal dorsal horn. In addition, the expression of iPLA2 was co-localized with astrocytes and neurons on the ipsilateral side of the dorsal horn in rats that underwent spinal nerve ligation. DISCUSSION: These data suggest that selective iPLA2 inhibitor produce analgesia in neuropathic rats by reducing central sensitization in the dorsal horn.

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.

Mirogabalin: could it be the next generation gabapentin or pregabalin?

Except for carbamazepine for trigeminal neuralgia, gabapentinoid anticonvulsants have been the standard for the treatment of neuropathic pain. Pregabalin, which followed gabapentin, was developed with the benefit of rapid peak blood concentration and better bioavailability. Mirogabalin besylate (DS-5565, Tarlige®) shows greater sustained analgesia due to a high affinity to, and slow dissociation from, the α2δ-1 subunits in the dorsal root ganglion (DRG). Additionally, it produces a lower level of central nervous system-specific adverse drug reactions (ADRs), due to a low affinity to, and rapid dissociation from, the α2δ-2 subunits in the cerebellum. Maximum plasma concentration is achieved in less than 1 hour, compared to 1 hour for pregabalin and 3 hours for gabapentin. The plasma protein binding is relatively low, at less than 25%. As with all gabapentinoids, it is also largely excreted via the kidneys in an unchanged form, and so the administration dose should also be adjusted according to renal function. The equianalgesic daily dose for 30 mg of mirogabalin is 600 mg of pregabalin and over 1,200 mg of gabapentin. The initial adult dose starts at 5 mg, given orally twice a day, and is gradually increased by 5 mg at an interval of at least a week, to 15 mg. In conclusion, mirogabalin is anticipated to be a novel, safe gabapentinoid anticonvulsant with a greater therapeutic effect for neuropathic pain in the DRG and lower ADRs in the cerebellum.

Use of anticonvulsants and antidepressants for treatment of complex regional pain syndrome: a literature review.

Complex regional pain syndrome (CRPS) is characterized by pain accompanied by symptoms including skin changes, sensory, motor, trophic changes and autonomic dysfunction. Anticonvulsants and antidepressants are commonly prescribed for neuropathic pain conditions; however, evidence is sparse whether these drugs are effective in reducing CRPS-related pain. As such, Pubmed was searched for studies published from January 1990 through March 2020; 13 studies were included in this review. Overall, evidence is considered insufficient for use of gabapentinoids for CRPS-related pain. However, three randomized controlled trials (RCTs) did find gabapentin to result in significant improvement in pain whereas one RCT reported use of amitriptyline to be equally as effective as gabapentin. Multiple case reports discussing the efficacy of pregabalin in pediatric CRPS patients, with relatively short duration of disease and underlying psychiatric illness, have been reported, but these findings need to be validated with RCTs.

Blockers of Wnt3a, Wnt10a, or ß-Catenin Prevent Chemotherapy-Induced Neuropathic Pain In Vivo.

Although chemotherapy is a key cancer treatment, many chemotherapeutic drugs produce chronic neuropathic pain, called chemotherapy-induced neuropathic pain (CINP), which is a dose-limiting adverse effect. To date, there is no medicine that prevents CINP in cancer patients and survivors. We determined whether blockers of the canonical Wnt signaling pathway prevent CINP. Neuropathic pain was induced by intraperitoneal injection of paclitaxel (PAC) on four alternate days in male Sprague-Dawley rats or male Axin2-LacZ knock-in mice. XAV-939, LGK-974, and iCRT14, Wnt/ß-catenin blockers, were administered intraperitoneally as a single or multiple doses before or after injury. Mechanical allodynia, phosphoproteome profiling, Wnt ligands, and inflammatory mediators were measured by von Frey filament, phosphoproteomics, reverse transcription-polymerase chain reaction, and Western blot analysis. Localization of ß-catenin was determined by immunohistochemical analysis in the dorsal root ganglia (DRGs) in rats and human. Our phosphoproteome profiling of CINP rats revealed significant phosphorylation changes in Wnt signaling components. Importantly, repeated systemic injections of XAV-939 or LGK-974 prevented the development of CINP in rats. In addition, XAV-939, LGK-974, and iCRT14 ameliorated CINP. PAC increased Wnt3a and Wnt10a, activated ß-catenin in DRG, and increased monocyte chemoattractant protein-1 and interleukin-1ß in DRG. PAC also upregulated rAxin2 in mice. Furthermore, ß-catenin was expressed in neurons, including calcitonin gene-related protein-expressing neurons and satellite cells in rat and human DRG. In conclusion, chemotherapy increases Wnt3a, Wnt10a, and ß-catenin in DRG and their pharmacological blockers prevent and ameliorate CINP, suggesting a target for the prevention and treatment of CINP.