Injectable Biologics for Neuropathic Pain: A Systematic Review.

BACKGROUND: Neuropathic pain is a complex condition that can be refractory to conventional management and can cause persistent suffering in patients. Current pharmacologic treatments can provide temporary symptomatic relief; however, the mechanism of these therapies does not address the underlying cause of neuropathic pain. The use of injectable biologics for neuropathic pain has multiple proposed mechanisms for analgesia including attenuation of inflammatory mediated processes, arrest or delay of the degenerative process, inhibition of apoptotic pathways, and augmentation of the survival and recovery of injured and uninjured nerves. STUDY DESIGN: A systematic review of human studies involving the use of injectable biologics for neuropathic pain. METHODS: A comprehensive search of several data bases including Ovid MEDLINE ® and Epub Ahead of Print, In Process & Other Non-Indexed Citations and Daily, and Ovid Embase from inception to November 24, 2020. RESULTS: The initial search yielded 3,450 studies with an additional 6 studies identified through other resources. Twenty-seven studies were included after independent review by two of the investigators. The included studies assessed the efficacy of injectable biologics for the treatment of neuropathic pain defined as pain reduction. Secondary outcome measures included functional improvement as well as safety of the procedures. A qualitative assessment of the literature without meta-analysis was performed due to the heterogeneity of the data. CONCLUSION: According to the GRADE criteria, there is very low certainty of evidence in support of the efficacy of injectable biologics for treatment of neuropathic pain. Future efforts should focus on creating a standardized methodology and study design with respect to preparation, dosage and route of administration of biologics. This will serve as a catalyst for higher quality randomized trials with generation of more useful data to help drive informed clinical decision making.

Chemogenetic manipulation of microglia inhibits neuroinflammation and neuropathic pain in mice.

Microglia play an important role in the central sensitization and chronic pain. However, a direct connection between microglial function and pain development in vivo remains incompletely understood. To address this issue, we applied chemogenetic approach by using CX3CR1creER/+:R26LSL-hM4Di/+ transgenic mice to enable expression of inhibitory Designer Receptors Exclusively Activated by Designer Drugs (Gi DREADD) in microglia. We found that microglial Gi DREADD activation inhibited spinal nerve transection (SNT)-induced microglial reactivity as well as chronic pain in both male and female mice. Gi DREADD activation downregulated the transcription factor interferon regulatory factor 8 (IRF8) and its downstream target pro-inflammatory cytokine interleukin 1 beta (IL-1ß). Using in vivo spinal cord recording, we found that activation of microglial Gi DREADD attenuated synaptic transmission following SNT. Our results demonstrate that microglial Gi DREADD reduces neuroinflammation, synaptic function and neuropathic pain after SNT. Thus, chemogenetic approaches provide a potential opportunity for interrogating microglial function and neuropathic pain treatment.

Fibromyalgia Symptom Severity and Psychosocial Outcomes in Fibromyalgia Patients with Hypovitaminosis D: A Prospective Questionnaire Study.

OBJECTIVE: To evaluate the association between hypovitaminosis D and outcomes of symptom severity, mood disorders, fatigue, and quality of life in fibromyalgia (FM) patients. METHODS: Five hundred ninety-three FM patients were surveyed from May 2012 to November 2013. Patients with serum vitamin D <25 ng/mL were considered to have hypovitaminosis D. The primary outcome was FM symptom severity (FIQ-R questionnaire). Secondary outcomes included quality of life (SF-36), fatigue (MFI-20), anxiety (GAD-7), and depression (PHQ-9). Independent t tests and chi-square tests were performed for continuous and categorical variables, respectively. Regression analysis was performed adjusting for age, gender, body mass index, ethnicity, and season. A post hoc analysis examined for correlation between outcomes and serum vitamin D (ng/mL) as a continuous variable. RESULTS: One hundred twenty-two patients (20.6%) had hypovitaminosis D. In our adjusted regression analysis, the total FIQ-R score in patients with hypovitaminosis D was higher compared with control patients with adequate serum vitamin D (57.85 ± 18.09 vs 62.79 ± 18.10, P = 0.04). Adjusted regression analysis revealed higher total GAD-7 (P = 0.01) and higher total PHQ-9 scores (P = 0.04) in patients with hypovitaminosis D compared with control patients. There were no differences based on severity of depression or anxiety. No differences in fatigue or quality of life were identified. Unadjusted post hoc analysis revealed that as serum vitamin D increased, there was an association with lower total FIQ-R (ß coefficient = -0.11, P = 0.02) and lower SF-36 subscale scores of role-physical (ß coefficient = -0.10, P = 0.03). Adjusted post hoc analysis revealed no significant associations. CONCLUSIONS: Hypovitaminosis D may be a risk factor for worse symptom severity, anxiety, and depression in FM patients.

Office-Based Mesenchymal Stem Cell Therapy for the Treatment of Musculoskeletal Disease: A Systematic Review of Recent Human Studies.

BACKGROUND: The use of mesenchymal stem cells (MSCs) in clinical applications for the treatment of musculoskeletal disease is steadily increasing in office-based practice. The so-called "first generation" of MSCs is defined as autologous stem cells that have undergone minimal manipulation and are used for a homologous purpose. Systematic reviews of the clinical trials completed to date of such MSCs enable practitioners to better understand what is currently known about the outcomes and side effects of such treatments. STUDY DESIGN: A systematic review of human clinical studies of office-based MSC therapy for the treatment of painful degenerative musculoskeletal conditions. METHODS: A search of the Ovid MEDLINE, EMBASE, and Scopus databases was conducted from 2006 through September 2016. Seven hundred sixty-one records were identified from database searching, and two records from reference review of included papers. Studies with human subjects that evaluated treatment of musculoskeletal disease with minimally manipulated MSCs were included. RESULTS: Eight studies were included in this review based on selection criteria. A total of 941 patients were included, 841 of whom received cellular products, and no significant adverse events were reported. Symptomatology generally improved, though no differences were seen over controls where present. CONCLUSION: Support in the literature is strongest for the use of bone marrow aspirate concentrate (BMAC) injections for the treatment of knee pain, but applications of the use of BMAC and peripheral blood-derived MSCs for the treatment of hip pain, tendon pain, and disc pain have all been reported. Further research is required, with large randomized controlled trials.

MicroRNA Quantitation During Dendritic Cell Endocytosis Using Imaging Flow Cytometry: Key Factors and Requirements.

BACKGROUND/AIMS: MicroRNA (miRNA)-induced suppression of dendritic cells (DCs) has been implicated in many diseases. Therefore, accurate monitoring of miRNA endocytosis by DCs is important for understanding the role of miRNAs in many diseases. Recently, a method for measuring the co-localization of Argonaute 2 (AGO2)-associated miRNAs on laser-scanning confocal microscopy method was proposed to localize the miRNAs. But its definition was limited by the number of observed cells through its accuracy. METHODS: In this study, a method based on imaging flow cytometry was developed to localize miR-590-5p with fluorescent probes in DCs. miR-590-5p proven to play an important role in tumor immunity. This method enabled the quantification, visualization and localization of the fluorescence intensity in 30,000 individual cells. RESULTS: Using this method, the DCs with different endocytotic ability were distinguished. The behaviour of miR-590-5p during endocytosis under the stimulation of tumor antigen in DCs was observed, binding to its cognate target mRNA and degradation in DCs. CONCLUSION: This method based on imaging flow cytometry provide an additional method to study miRNA processing in DCs, which makes it a valuable addition to existing miRNA research techniques.

The Effect of Epidural Steroid Injections on Bone Mineral Density and Vertebral Fracture Risk: A Systematic Review and Critical Appraisal of Current Literature.

Objective: The aim of this paper is to review the available literature investigating the effect of epidural steroid injections (ESIs) on bone mineral density (BMD) and vertebral fracture risk. Study design: Systematic review of current literature. Methods: The sources of the data were PubMed, Embase, Cochrane, and Scopus. Papers included in the review were original research articles in peer-reviewed journals. Results: A total of 7,233 patients (eight studies) with a mean age ranging between 49 and 74 years and an average follow-up between six and 60 months were studied. Steroids that were used included triamcinolone, dexamethasone, and methylprednisolone (MP), with a mean number of injections ranging from one to 14.7 and an average cumulative dose in MP equivalents between 80 and 8,130 mg. Epidural steroids were associated with significantly decreased BMD in four out of six included studies, and with increased risk of vertebral fracture in one out of two included studies. Significant reductions in BMD were associated with a cumulative MP dose of 200 mg over a one-year period and 400 mg over three years, but not in doses of less than 200 mg of MP equivalents for postmenopausal women and at least 3 g for healthy men. The risk of osteopenia and osteoporosis was lower in patients who were receiving anti-osteoporotic medication during the treatment course. Conclusions: ESIs should be recommended with caution, especially in patients at risk for osteoporotic fractures, such as women of postmenopausal age. Anti-osteoporotic medication might be considered prior to ESI.

Spinal Cord Stimulator Implant Infection Rates and Risk Factors: A Multicenter Retrospective Study.

OBJECTIVES: Spinal cord stimulation is an evidence-based treatment for a number of chronic pain conditions. While this therapy offers improvement in pain and function it is not without potential complications. These complications include device failure, migration, loss of therapeutic paresthesia, and infection. This article looked to establish a modern infection rate for spinal cord stimulators, assess the impact of known risk factors for surgical site infections and to determine the impact of certain preventative measures on the rate of infection. METHODS: After institutional review board approval, a multisite, retrospective review was conducted on 2737 unique implants or revisions of SCS systems. Patient demographics, risk factors including diabetes, tobacco use, obesity, revision surgery, trial length, implant location, implant type, surgeon background, prophylactic antibiotic use, utilization of a occlusive dressing, and post-operative antibiotic use were recorded and analyzed. RESULTS: The overall infection rate was 2.45% (n = 67). Diabetes, tobacco use, and obesity did not independently increase the rate of infection. Revision surgeries had a trend toward higher infection rate; however, this did not meet statistical significance. There was no difference in the rate of infection between implants performed by physicians of different base specialties, cylinder leads vs. paddle leads, or between different prophylactic antibiotics. Implants performed at academic centers had a higher rate of infection when compared to implants performed in nonacademic settings. When patients received an occlusive dressing or post-operative antibiotics they had a lower rate of infection. CONCLUSIONS: The infection rate (2.45%) reported in this study is lower than the previously reported rates (3-6%) and are on par with other surgical specialties. This study did not show an increased rate of infection for patients that used tobacco, had diabetes or were obese. It's possible that given the low overall infection rate a larger study is needed to establish the true impact of these factors on infection. In addition, this study did not address the impact of poorly controlled diabetes mellitus (elevated hemoglobin A1c) vs. well-controlled diabetes. It can be concluded from this study that utilizing an occlusive dressing over the incision in the post-operative period decreases the rate of infection and should become the standard of care. This study also demonstrated the positive impact of post-operative antibiotics in decreasing the rate of infection. Studies in other surgical specialties have not shown this impact which would suggest that further research is needed.

Spinal Cord Stimulator Related Infections: Findings From a Multicenter Retrospective Analysis of 2737 Implants.

INTRODUCTION: Surgical site infection is a potential complication of spinal cord stimulator (SCS) implantation. Current understanding of the epidemiology, diagnosis, and treatment of these infections is based largely on small clinical studies, many of which are outdated. Evidence-based guidelines for management of SCS-related infections thus rely instead on expert opinion, case reports, and case series. In this study, we aim to provide a large scale retrospective study of infection management techniques specifically for SCS implantation. METHODS: A multicenter retrospective study of SCS implants performed over a seven-year period at 11 unique academic and non-academic institutions in the United States. All infections and related complications in this cohort were analyzed. RESULTS: Within our study of 2737 SCS implant procedures, we identified all procedures complicated by infection (2.45%). Localized incisional pain and wound erythema were the most common presenting signs. Laboratory studies were performed in the majority of patients, but an imaging study was performed in less than half of these patients. The most common causative organism was Staphylococcus aureus and the IPG pocket was the most common site of an SCS-related infection. Explantation was ultimately performed in 52 of the 67 patients (77.6%). Non-explantation salvage therapy was attempted in 24 patients and was successful in resolving the infection in 15 patients without removal of SCS hardware components. DISCUSSION: This study provides current data regarding SCS related infections, including incidence, diagnosis, and treatment.

Safety of Lumbar Spine Radiofrequency Procedures in Patients Who Have Posterior Spinal Hardware.

OBJECTIVE: The purpose of this study was to determine whether the energy generated by an active radiofrequency (RF) cannula adjacent to lumbar spine hardware could result in heating of the hardware. DESIGN: Prospective study. SETTING: Tertiary care medical center. SUBJECTS: Six patients with lumbar facet joint pain at the level adjacent to lumbar spine fusion hardware were studied. METHODS: A total of 10 lumbar medial branch nerve radiofrequency lesion procedures were performed on six patients. A temperature probe was placed on the fusion hardware to continuously monitor the temperature of the hardware throughout the RF procedure. RESULTS: The temperature of the fusion hardware increased in six of the 10 RF lesion procedures. During two of the procedures, the temperature rose rapidly to 42°C, at which time the procedure was ceased at that level. CONCLUSION: This study demonstrated that radiofrequency lesioning to treat symptomatic facet joint pain in patients who have adjacent posterior lumbar fusion hardware may result in heat energy being transferred to the adjacent hardware. This may increase the risk of injury to the patient. Monitoring for a temperature increase is easily accomplished by inserting a temperature probe onto the surface of the hardware.

Patient Outcomes and Spinal Cord Stimulation: A Retrospective Case Series Evaluating Patient Satisfaction, Pain Scores, and Opioid Requirements.

INTRODUCTION: Spinal cord stimulators (SCS) are used to treat various chronic pain states. Establishing patient outcomes in terms of pain control, opioid medication use, and overall satisfaction is vital in maintaining SCS's role in clinical practice. METHODS: All patients who underwent SCS implantation between January 2001 and December 2011 at a tertiary academic pain medicine center were included if he or she underwent permanent cervical or thoracolumbar dorsal column SCS implantation and age was 18 or greater. For the 199 patients who met inclusion criteria, data were collected retrospectively. Preimplant information included indication for implantation, Numeric Rating Scale (NRS) score, and dose in oral morphine equivalents (OME). Postimplant NRS score was recorded at 6 months and 1 year. OME requirement and patient satisfaction were determined at 1 year postimplantation. RESULTS: This data set showed an overall decrease in OME requirements and NRS scores at both 6 months and 1 year. These differences were statistically significant (P < 0.01) compared to preimplantation values. Additionally, 84.27% of patients were satisfied with their implants at 1 year. Patient outcomes were analyzed further in respect to implant indication; groups included failed back surgery syndrome (FBSS), complex regional pain syndrome (CRPS), angina, and other. For all groups, there were statistically significant (P < 0.01) decreases in NRS scores at 6 months and 1 year. In the FBSS and CRPS groups, statistically significant (P < 0.02) decreases in OME usage existed. CONCLUSION: Retrospective review of patients with spinal cord stimulators revealed OME reduction at 1 year for those patients in the FBSS and CRPS groups; patient satisfaction at 1 year and NRS score reduction at 6 months and 1 year were statistically significant for all groups.

Improved perioperative analgesia with ultrasound-guided ilioinguinal/iliohypogastric nerve or transversus abdominis plane block for open inguinal surgery: a systematic review and meta-analysis of randomized controlled trials.

[Purpose] Ultrasound-guided ilioinguinal/iliohypogastric (II/IH) nerve and transversus abdominis plane (TAP) blocks have been increasingly utilized in patients for perioperative analgesia. We conducted this meta-analysis to evaluate the clinical efficacy of ultrasound-guided II/IH nerve or TAP blocks for perioperative analgesia in patients undergoing open inguinal surgery. [Subjects and Methods] A systematic search was conducted of 7 databases from the inception to March 5, 2015. Randomized controlled trials (RCTs) comparing the clinical efficacy of ultrasound-guided vs. landmark-based techniques to perform II/IH nerve and TAP blocks in patients with open inguinal surgery were included. We constructed random effects models to pool the standardized mean difference (SMD) for continuous outcomes and the odds ratio (OR) for dichotomized outcomes. [Results] Ultrasound-guided II/IH nerve or TAP blocks were associated with a reduced use of intraoperative additional analgesia and a significant reduction of pain scores during day-stay. The use of rescue drugs was also significantly lower in the ultrasound-guided group. [Conclusion] The use of ultrasound-guidance to perform an II/IH nerve or a TAP block was associated with improved perioperative analgesia in patients following open inguinal surgery compared to landmark-based methods.

Evaluation and management of knee osteoarthritis.

Knee osteoarthritis (KOA) significantly contributes to the global disability burden, with its incidence expected to escalate by 74.9% by 2050. The urgency to comprehend and tackle this condition is critical, necessitating an updated and thorough review of KOA. A systematic review up to February 26, 2024, has elucidated the principal aspects of KOA's pathogenesis, risk factors, clinical manifestations, and contemporary management paradigms. The origins of KOA are intricately linked to mechanical, inflammatory, and metabolic disturbances that impair joint function. Notable risk factors include age, obesity, and previous knee injuries. Diagnosis predominantly relies on clinical assessment, with radiographic evaluation reserved conditionally. The significance of rehabilitation assessments, informed by the International Classification of Functioning, Disability, and Health framework, is highlighted. Treatment strategies are diverse, prioritizing nonpharmacological measures such as patient education, exercise, and weight management, with pharmacological interventions considered adjuncts. Intra-articular injections and surgical options are contemplated for instances where conventional management is inadequate. KOA stands as a predominant disability cause globally, characterized by a complex etiology and profound effects on individuals' quality of life. Early, proactive management focusing on nonpharmacological interventions forms the cornerstone of treatment, aiming to alleviate symptoms and enhance joint function. This comprehensive review underscores the need for early diagnosis, individualized treatment plans, and the integration of rehabilitation assessments to optimize patient outcomes. Further research is needed to refine prevention strategies and improve management outcomes for KOA patients.

Intrathecal delivery of adipose-derived mesenchymal stem cells in traumatic spinal cord injury: Phase I trial.

Intrathecal delivery of autologous culture-expanded adipose tissue-derived mesenchymal stem cells (AD-MSC) could be utilized to treat traumatic spinal cord injury (SCI). This Phase I trial (ClinicalTrials.gov: NCT03308565) included 10 patients with American Spinal Injury Association Impairment Scale (AIS) grade A or B at the time of injury. The study's primary outcome was the safety profile, as captured by the nature and frequency of adverse events. Secondary outcomes included changes in sensory and motor scores, imaging, cerebrospinal fluid markers, and somatosensory evoked potentials. The manufacturing and delivery of the regimen were successful for all patients. The most commonly reported adverse events were headache and musculoskeletal pain, observed in 8 patients. No serious AEs were observed. At final follow-up, seven patients demonstrated improvement in AIS grade from the time of injection. In conclusion, the study met the primary endpoint, demonstrating that AD-MSC harvesting and administration were well-tolerated in patients with traumatic SCI.

Multidisciplinary Management Strategies for Long COVID: A Narrative Review.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused millions of infections to date and has led to a worldwide pandemic. Most patients had a complete recovery from the acute infection, however, a large number of the affected individuals experienced symptoms that persisted more than 3 months after diagnosis. These symptoms most commonly include fatigue, memory difficulties, brain fog, dyspnea, cough, and other less common ones such as headache, chest pain, paresthesias, mood changes, muscle pain, and weakness, skin rashes, and cardiac, endocrine, renal and hepatic manifestations. The treatment of this syndrome remains challenging. A multidisciplinary approach to address combinations of symptoms affecting multiple organ systems has been widely adopted. This narrative review aims to bridge the gap surrounding the broad treatment approaches by providing an overview of multidisciplinary management strategies for the most common long COVID conditions.

Botulinum toxin type A reduces hyperalgesia and TRPV1 expression in rats with neuropathic pain.

OBJECTIVE: We aim to determine the effects of botulinum toxin type A (BTX-A) on the thresholds of pain and the expression of transient receptor potential vanilloid type 1 (TRPV1) in the dorsal root ganglion (DRG) in rats with neuropathic pain induced by selective ventral root transection (VRT). METHODS: Neuropathic pain was induced by transection of the lumbar 5 ventral root in male Sprague-Dawley rats. BTX-A or saline was administered to the plantar surface by subcutaneous injection. SB366791 (an inhibitor of TRPV1) was administered intraperitoneally. Behavioral tests were conducted preoperatively and at predefined postoperative days. The expression of TRPV1 was detected and quantified by immunohistochemistry and Western blotting at postoperative days 3, 7, 14, and 21. RESULTS: TRPV1 expression increased significantly in the L4 ∼5 dorsal root ganglia 7 days after L5 VRT compared with the sham-operated control (P < 0.05). This increase persisted for at least 21 days. The thresholds of foot withdrawal to mechanical and thermal stimulation decreased significantly as well. Subcutaneous injection of BTX-A significantly and dose-dependently reduced the expression of TRPV1 (P < 0.05) and partially reversed the pain thresholds. CONCLUSION: Upregulation of TRPV1 expression in the DRG is an important mechanism of neuropathic pain induced by the VRT. The analgesic effect of BTX-A is most likely mediated through reduction of TRPV1 expression in the nociceptors.

Autologous Platelet-Rich Plasma Applications in Chronic Pain Medicine: Establishing a Framework for Future Research - A Narrative Review.

BACKGROUND: During the last decades, platelet-rich plasma has been studied for the treatment of multiple chronic pain conditions, in addition to being employed in the enhancement of healing after tissue injury. OBJECTIVE: To establish a framework for future research regarding the utilization of platelet-rich plasma in the treatment of chronic tissue injuries. METHODS: Preclinical and clinical studies from 2000-2020 relevant to applications of platelet-rich plasma for the treatment of chronic pain conditions were extracted from PubMed and Medline databases. The studies were analyzed on the basis of the study population, type of intervention, method of platelet-rich plasma preparation, the number of treatments administered, the timeframe of injections, and clinical outcomes. RESULTS: Although several preclinical studies and double-blind, randomized trials have shown promising results in the application of platelet-rich plasma for the treatment of multiple chronic pain conditions, various studies have also reported controversial results. Additionally, the methods employed for obtaining the platelet-rich plasma have not been standardized between studies, resulting in different concentrations of blood components between the preparations utilized. Moreover, differences between studies were also found regarding the number of injections administered per treatment. CONCLUSIONS: Future research addressing the utilization of platelet-rich plasma in the treatment of chronic pain conditions should focus on shedding light on the following major questions: a) Is there a dose-effect relation between the platelet count and the clinical efficacy of the preparation?; b) What pathology determinants should be considered when selecting between leukocyte-enriched and leukocyte-depleted concentrates?; c) What is the role of platelet activation methods on the clinical efficacy of platelet-rich plasma?; d) Is there an optimal number of injections and time frame for application of multiple injection treatment cycles?; e) Does the addition of local anesthetics affect the clinical efficacy of platelet-rich plasma?; and f) Is there potential for future platelet-rich plasma applications for the treatment of neuropathic pain of peripheral origin?

Time-to-enrollment in clinical trials investigating neurological recovery in chronic spinal cord injury: observations from a systematic review and ClinicalTrials.gov database.

Currently, large numbers of clinical trials are performed to investigate different forms of experimental therapy for patients suffering from chronic spinal cord injury (SCI). However, for the enrollment process, there are different views on how the time period between injury and interventions should be determined. Herein, we sought to evaluate the impact of time-to-enrollment in chronic SCI clinical trials. A data set comprising 957 clinical studies from clinicalTrials.gov was downloaded and analyzed focusing on the eligibility criteria for post-injury time-to-enrollment. We also aggregated individual patient data from nine clinical trials of regenerative interventions for chronic SCI selected by a systematic literature search from 1990 to 2018. Characteristics of the studies were assessed and compared by dividing into three groups based on time-to-enrollment (group 1 ≤ 12 months, group 2 = 12-23 months and group 3 ≥ 24 months). In ClinicalTrials.gov registry, 445 trials were identified for chronic SCI where 87% (385) were unrestricted in the maximum post-injury time for trial eligibility. From systematic literature search, nine studies and 156 patients (group 1 = 30, group 2 = 55 and group 3 = 71) were included. The range of time-to-enrollment was 0.5 to 321 months in those studies. We also observed various degrees of motor and sensory improvement in between three time-to-enrollment groups. Our results indicate that enrolling wide ranges of time-to-enrollment in a group may present imprecise outcomes. Clinical trial designs should consider appropriate post-injury time frames to evaluate therapeutic benefit.

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.

Platelet Rich Plasma and Platelet-Related Products in the Treatment of Radiculopathy-A Systematic Review of the Literature.

Back pain with radicular symptoms is associated with detrimental physical and emotional functioning and economic burden. Conservative treatments including physical, pharmacologic and injection therapy may not provide clinically significant or long-standing relief. Regenerative medicine research including Platelet rich plasma (PRP), Platelet lysate (PL) or Plasma rich in growth factors (PRGF) continues to develop, however evidence appraisal for treatment of radicular pain remains lacking. Thus, we performed a systematic review to evaluate the effectiveness of epidural steroid injections containing PRP or related products to treat radicular pain. Embase, PubMed/MEDLINE, Cochrane Central Register of Controlled Trials (CENTRAL), and Google Scholar databases were queried. Twelve studies were included in qualitative analysis, consisting of three randomized controlled trials and nine observational studies. The primary outcome was pain intensity, and secondary outcomes included functional improvement, anatomical changes on advanced imaging, and adverse events. All studies identified improved pain intensity and functional outcomes after epidural injection of PRP, PRGF and/or PL. Similar or longer lasting pain relief was noted in the PRP cohort compared to the cohort receiving epidural steroid injections with effects lasting up to 12-24 months. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) analysis revealed a very-low certainty of evidence due to risk of bias, indirectness, and imprecision.

SPECT-CT as a Predictor of Pain Generators in Patients Undergoing Intra-Articular Injections for Chronic Neck and Back Pain.

BACKGROUND: The ability to accurately predict pain generators for chronic neck and back pain remains elusive. OBJECTIVE: We evaluated whether injections targeted at foci with uptake on single-photon emission computerized tomography-computed tomography (SPECT-CT) were associated with improved outcomes in patients with chronic neck and back pain. METHODS: A retrospective review was completed on patients undergoing SPECT-CT for chronic neck and back pain between 2016 and 2020 at a tertiary academic center. Patients' records were reviewed for demographic, clinical, imaging, and outcomes data. Only those patients who had facet injections after SPECT-CT were included in this evaluation. Patients undergoing injections targeted at foci of abnormal radiotracer uptake were compared with patients without uptake concerning immediate positive response, visual analog scale, and the need for additional injection or surgery at the target level. RESULTS: A total of 2849 patients were evaluated with a SPECT-CT for chronic neck and back pain. Of those, 340 (11.9%) patients received facet joint injections after SPECT-CT. A propensity score regression analysis adjusted for age, gender, body mass index, hypertension, multiple target injections, and injection location showed uptake targeted injections not being associated with an improved immediate positive response (odds ratio: 0.64; 95% confidence interval: 0.34-1.21; P = 0.172). In patients with a failed facet injection preceding SPECT-CT, adding SPECT-CT to guide facet injections was associated with a decrease in visual analog scale pain scores 2 weeks after injection (P = 0.018), particularly when changes were made to the facets being targeted (P = 0.010). CONCLUSION: This study suggests that there is benefit with SPECT-CT specially to guide facet injections after failed prior facet injections.