A comprehensive review of cell transplantation and platelet-rich plasma therapy for the treatment of disc degeneration-related back and neck pain: A systematic evidence-based analysis.

Low back pain (LBP) and neck pain predominate as the primary causes of disability. Cell- and platelet-rich plasma (PRP) products are potential therapies with clinical trials and reviews promoting their efficacy. Nonetheless, they frequently disregard the clinical significance of reported improvements. In this systematic review, the effectuated improvements in pain, disability, quality of life (QoL), and radiographic images are comprehensively described and scored on their clinical significance. An electronic database literature search was conducted on July 2023 for in-human assessment of cell or PRP products to alleviate discogenic pain. Papers were screened on quantitative pain, disability, QoL, radiographic improvements, and safety outcomes. Risk of bias was assessed through MINORS and Cochrane Source of Bias tools. Reported outcomes were obtained, calculated, and assessed to meet minimal clinically important difference (MCID) standards. From 7623 screened papers, a total of 80 articles met the eligibility criteria, presenting 68 specific studies. These presented at least 1974 treated patients. Overall, cell/PRP injections could alleviate pain and disability, resulting in MCID for pain and disability in up to a 2-year follow-up, similar to those observed in patients undergoing spinal fusion. Included trials predominantly presented high levels of bias, involved heterogeneous study designs, and only a minimal number of randomized controlled trials. Nonetheless, a clear clinically significant impact was observed for cell- and PRP-treated cohorts with overall good safety profiles. These results highlight a strong therapeutic potential but also underline the need for future cost-effectiveness assessments to determine the benefits of cell/PRP treatments.

The Role of Platelet Rich Plasma in Vertebrogenic and Discogenic Pain: A Systematic Review and Meta-Analysis.

PURPOSE OF REVIEW: The present investigation evaluates clinical uses and roles of platelet rich plasma in the management of vetrebrogenic and discogenic mediated pain states. RECENT FINDINGS: Back pain is a common and significant condition that affects millions of people around the world. The cause of back pain is often complex and multifactorial, with discogenic and vertebrogenic pain being two subtypes of back pain. Currently, there are numerous methods and modalities in which back pain is managed and treated such as physical therapy, electrical nerve stimulation, pharmacotherapies, and platelet-rich plasma. To conduct this systematic review, the authors used the keywords "platelet-rich plasma", "vertebrogenic pain", and "discogenic pain", on PubMed, EuroPMC, Who ICTRP, and clinicaltrials.gov to better elucidate the role of this treatment method for combating vertebrogenic and discogenic back pain. In recent decades, there has been a rise in popularity of the use of platelet-rich plasma for the treatment of numerous musculoskeletal conditions. Related to high concentration of platelets, growth factors, cytokines, and chemokines, platelet-rich plasma is effective in reducing pain related symptoms and in the treatment of back pain. Platelet-rich plasma use has evolved and gained popularity for pain related conditions, including vertebrogenic and discogenic back pain. Additional well-designed studies are warranted in the future to better determine best practice strategies to provide future clinicians with a solid foundation of evidence to make advancements with regenerative medical therapies such as platelet-rich plasma.

Evolving role of VIADISC for chronic low back and discogenic pain: a narrative review.

INTRODUCTION: Chronic lower back pain is a leading cause of disability and healthcare spending worldwide. Discogenic pain, pain originating from the intervertebral disk, is a common etiology of chronic lower back pain. Currently, accepted treatments for chronic discogenic pain focus only on the management of symptoms, such as pain. There are no approved treatments that stop or reverse degenerating intervertebral discs. Biologic therapies promoting disc regeneration have been developed to expand treatment options. VIADISC™ NP, is a viable disc allograft supplementation that, in a recent trial, demonstrated a significant reduction in pain and increased function in patients suffering from symptomatic degenerative disc disease. AREAS COVERED: This manuscript summarizes the epidemiology and etiology of low back pain, the pathophysiology of degenerative disc disease, current treatments, and a need for newer therapies. The rationale behind intradiscal biologics for the treatment of symptomatic degenerative disc disease is also discussed. EXPERT OPINION: Characterization of the biology leading to disc degeneration has allowed for the development of intradiscal biologics. They may soon be capable of preventing and reversing disc degeneration. Clinical trials have shown promise, but further research into efficacy and safety is needed before these therapies are widely employed.

Revolutionizing Back Pain Management: Is Epidural Platelet-Rich Plasma the Superior Choice Over Steroids?

Background and objective Low back discomfort is one of the main factors that restrict physical activity, and it is becoming more and more common. Surgery is the best option when all other conservative treatment methods have failed, but it is not a panacea. While local anesthetic-free and combined epidural steroid injections have been used for many years, their usefulness is limited to shorter periods. In the field of orthopedics, platelet-rich plasma (PRP) has gained widespread recognition as an adjuvant component. PRP has been applied to improve tissue repair, both soft and hard. This comparative study aimed to evaluate the potential of PRP as a therapy for low back pain (LBP). Methods We included 64 adult individuals with complaints of LBP. They were classified into two groups: group A underwent a single injection in the afflicted lumbar intervertebral disc (IVD) level with 1.5 ml of methylprednisolone, 1.5 ml 2% lidocaine, and 0.5 ml of saline under rigorous aseptic precautions; in contrast, group B was administered a single injection of 3 milliliters of autologous PRP. Patients' scores on the visual analog scale (VAS), the Modified Oswestry Disability Questionnaire (MODQ), and the Straight Leg Raising Test (SLRT) were assessed before and during therapy. Results The data gathered were subjected to statistical analysis. Statistically significant differences were found in the VAS scores between group A (methylprednisolone group) and group B (PRP group) post-one hour (6.0 ±0.74 vs. 6.92 ±0.57) and after three months (5.2 ±0.65 vs. 3.26 ±0.79). Conclusions Our study revealed gradual progressive improvement in the symptoms of patients in the PRP group as indicated by scores on SLRT, VAS, and MODQ. The results were comparable to those who received methylprednisolone injections. There was a statistically significant difference in VAS scores between the two groups, with the PRP group reporting a higher degree of pain reduction, showing that PRP is an effective alternative to epidural steroid infiltration in managing chronic LBP.

[Translated article] Frequency of use of discography findings for the diagnosis of low back pain of discogenic origin. Systematic review of the literature.

INTRODUCTION: There are different techniques and interpretations of discography findings to determine it positive for the diagnosis of discogenic pain. This study aims to evaluate the frequency of use of discography findings for the diagnosis of low back pain of discogenic origin. MATERIAL AND METHODS: A systematic review of the literature of the last 17 years was performed in MEDLINE and BIREME. A total of 625 articles were identified, 555 were excluded for duplicates, title and abstract. We obtained 70 full texts of which 36 were included in the analysis after excluding 34 for not meeting the inclusion criteria. RESULTS: Among the criteria in discography to determine it as positive, 8 studies used only the pain response to the procedure, 28 studies used more than one criterion during discography to consider it as positive, the evaluation of at least one adjacent intervertebral disc with a negative result was necessary in 26 studies to consider a discography as positive. Five studies formally expressed the use of the technique described by SIS/IASP to determine a discography as positive. CONCLUSIONS: Pain in response to contrast medium injection, assessed with the visual analogue pain scale ≥6, was the most used criterion in the studies included in this review. Although there are already criteria to determine a discography as positive, the use of different techniques and interpretations of discography findings to determine a positive discography for low back pain of discogenic origin persists.

Acute back pain: Clinical and radiologic diagnosis: WFNS spine committee recommendations.

Objective: To formulate the most current, evidence-based recommendations for the clinical and radiologic diagnosis of acute low back pain lasting <4 weeks. Methods: A systematic literature search in PubMed and Google Scholar databases was performed from 2012 to 2022 using the search terms "acute back pain AND clinical diagnosis" and "acute back pain AND radiologic diagnosis". Screening criteria resulted in a total of 97 papers analyzed. Using the Delphi method and two rounds of voting, the WFNS (World Federation of Neurosurgical Societies) Spine Committee generated ten final consensus statements. Results: Ten final consensus statements address the clinical diagnosis of acute LBP, including which clinical conditions cause acute LBP and how we can distinguish between the different causes of LBP, including discogenic, facet joint, sacroiliac joint, and myofascial pain. The most important step for the radiologic diagnosis of acute LBP is to evaluate the necessity of radiologic investigation, as well as its timing and the most appropriate type of imaging modality. Importantly, imaging should not be a routine diagnostic tool, unless red flag signs are present. In fact, routine imaging for acute LBP can actually have a negative effect as it may reveal incidental radiographic findings that exacerbate patient fear and anxiety. Conclusion: Overall, the quality of evidence is not high for most of our consensus statements, and further studies are needed to validate the WFNS Spine Committee recommendations on the clinical and radiographic diagnosis of acute LBP.

Annulus Fibrosus Injury Induces Acute Neuroinflammation and Chronic Glial Response in Dorsal Root Ganglion and Spinal Cord-An In Vivo Rat Discogenic Pain Model.

Chronic painful intervertebral disc (IVD) degeneration (i.e., discogenic pain) is a major source of global disability needing improved knowledge on multiple-tissue interactions and how they progress in order improve treatment strategies. This study used an in vivo rat annulus fibrosus (AF) injury-driven discogenic pain model to investigate the acute and chronic changes in IVD degeneration and spinal inflammation, as well as sensitization, inflammation, and remodeling in dorsal root ganglion (DRG) and spinal cord (SC) dorsal horn. AF injury induced moderate IVD degeneration with acute and broad spinal inflammation that progressed to DRG to SC changes within days and weeks, respectively. Specifically, AF injury elevated macrophages in the spine (CD68) and DRGs (Iba1) that peaked at 3 days post-injury, and increased microglia (Iba1) in SC that peaked at 2 weeks post-injury. AF injury also triggered glial responses with elevated GFAP in DRGs and SC at least 8 weeks post-injury. Spinal CD68 and SC neuropeptide Substance P both remained elevated at 8 weeks, suggesting that slow and incomplete IVD healing provides a chronic source of inflammation with continued SC sensitization. We conclude that AF injury-driven IVD degeneration induces acute spinal, DRG, and SC inflammatory crosstalk with sustained glial responses in both DRGs and SC, leading to chronic SC sensitization and neural plasticity. The known association of these markers with neuropathic pain suggests that therapeutic strategies for discogenic pain need to target both spinal and nervous systems, with early strategies managing acute inflammatory processes, and late strategies targeting chronic IVD inflammation, SC sensitization, and remodeling.

Non-Surgical Approaches to the Management of Lumbar Disc Herniation Associated with Radiculopathy: A Narrative Review.

Lumbar disc herniation associated with radiculopathy (LDHR) is among the most frequent causes of spine-related disorders. This condition is triggered by irritation of the nerve root caused by a herniated disc. Many non-surgical and surgical approaches are available for managing this prevalent disorder. Non-surgical treatment approaches are considered the preferred initial management methods as they are proven to be efficient in reducing both pain and disability in the absence of any red flags. The methodology employed in this review involves an extensive exploration of recent clinical research, focusing on various non-surgical approaches for LDHR. By exploring the effectiveness and patient-related outcomes of various conservative approaches, including physical therapy modalities and alternative therapies, therapists gain valuable insights that can inform clinical decision-making, ultimately contributing to enhanced patient care and improved outcomes in the treatment of LDHR. The objective of this article is to introduce advanced and new treatment techniques, supplementing existing knowledge on various conservative treatments. It provides a comprehensive overview of the current therapeutic landscape, thereby suggesting pathways for future research to fill the gaps in knowledge. Specific to our detailed review, we identified the following interventions to yield moderate evidence (Level B) of effectiveness for the conservative treatment of LDHR: patient education and self-management, McKenzie method, mobilization and manipulation, exercise therapy, traction (short-term outcomes), neural mobilization, and epidural injections. Two interventions were identified to have weak evidence of effectiveness (Level C): traction for long-term outcomes and dry needling. Three interventions were identified to have conflicting or no evidence (Level D) of effectiveness: electro-diagnostic-based management, laser and ultrasound, and electrotherapy.

Preclinical Animal Study and Pilot Clinical Trial of Using Enriched Peripheral Blood-Derived Mononuclear Cells for Intervertebral Disc Degeneration.

Low back pain (LBP) is a leading cause of long-term disability globally. Intervertebral disk degeneration (IVDD) is mainly responsible for discogenic pain in LBP-affected young patients. There is no effective therapy to reverse disease severity and IVDD progression. This study investigates the effect of human peripheral blood-derived mononuclear cells (PBMCs) on pain relief and life quality improvement in IVDD patients. The enriched monocytes of the PBMCs could differentiate into CD14 and CD206 double-positive M2 macrophages in vitro. Preclinical evidence in rats showed that the transplanted PBMCs exhibited anti-inflammatory and moderate tissue-repair effects on controlling IVDD progress in the rat model. The PBMCs significantly steered the aggrecan and type II collagen expressions and attenuated the pro-inflammatory cytokines in the affected disk. Based on the animal results, 36 patients with chronic low back pain (CLBP) were included in clinical trials. The control group was conservative care only, and the experimental group was platelet-rich plasma (PRP) and PBMCs intradiscal injections. We first confirmed the single lumbar disk causing the discogenic pain by provocative discography or magnetic resonance imaging (MRI). Discogenic LBP participants received one intradiscal injection of autologous PBMCs and followed for 6 months. Our clinical trial showed that patients' LBP and disability were significantly ameliorated after the PBMCs transplantation rather than PRP. These preclinical and pilot clinical studies indicate that intradiscal injection of the enriched PBMCs might be a feasible and potential cell therapy to control pain and disability in IVDD patients.

An Engineered Bionic Nanoparticle Sponge as a Cytokine Trap and Reactive Oxygen Species Scavenger to Relieve Disc Degeneration and Discogenic Pain.

The progressive worsening of disc degeneration and related nonspecific back pain are prominent clinical issues that cause a tremendous economic burden. Activation of reactive oxygen species (ROS) related inflammation is a primary pathophysiologic change in degenerative disc lesions. This pathological state is associated with M1 macrophages, apoptosis of nucleus pulposus cells (NPC), and the ingrowth of pain-related sensory nerves. To address the pathological issues of disc degeneration and discogenic pain, we developed MnO2@TMNP, a nanomaterial that encapsulated MnO2 nanoparticles with a TrkA-overexpressed macrophage cell membrane (TMNP). Consequently, this engineered nanomaterial showed high efficiency in binding various inflammatory factors and nerve growth factors, which inhibited inflammation-induced NPC apoptosis, matrix degradation, and nerve ingrowth. Furthermore, the macrophage cell membrane provided specific targeting to macrophages for the delivery of MnO2 nanoparticles. MnO2 nanoparticles in macrophages effectively scavenged intracellular ROS and prevented M1 polarization. Supportively, we found that MnO2@TMNP prevented disc inflammation and promoted matrix regeneration, leading to downregulated disc degenerative grades in the rat injured disc model. Both mechanical and thermal hyperalgesia were alleviated by MnO2@TMNP, which was attributed to the reduced calcitonin gene-related peptide (CGRP) and substance P expression in the dorsal root ganglion and the downregulated Glial Fibrillary Acidic Protein (GFAP) and Fos Proto-Oncogene (c-FOS) signaling in the spinal cord. We confirmed that the MnO2@TMNP nanomaterial alleviated the inflammatory immune microenvironment of intervertebral discs and the progression of disc degeneration, resulting in relieved discogenic pain.

Mesenchymal stem cells and thermal annular procedures for discogenic pain: a systematic review with pooled analysis.

Aim: Compare the effectiveness of mesenchymal stem cell injection therapies (MSC) and thermal annular procedures for the treatment of discogenic lower back pain. Materials & methods: A systematic review was performed following PRISMA 2020 guidelines. Pooled analysis was performed using patients' pain scores at baseline and at 12 months post-intervention. Results: Effect sizes based on change in pain score from baseline to 12 month follow-up revealed clinically significant improvement in pain score across all interventions. Conclusion: Minimally invasive interventions provide meaningful relief in discogenic back pain, with results suggesting promise for MSC injection therapies as a treatment model.

Imaging of Discogenic and Vertebrogenic Pain.

Chronic low back pain is a major source of pain and disability globally involving multifactorial causes. Historically, intervertebral disc degeneration and disruption have been associated as primary back pain triggers of the anterior column, termed "discogenic pain." Recently, the vertebral endplates have been identified as another possible pain trigger of the anterior column. This "endplate-driven" model, defined "vertebrogenic pain," is often interconnected with disc degeneration. Diagnosis of vertebrogenic and discogenic pain relies on imaging techniques that isolate pain generators and exclude comorbid conditions. Traditional methods, like radiographs and discography, are augmented by more sensitive methods, including SPECT, CT, and MRI. Morphologic MRI is pivotal in revealing indicators of vertebrogenic (eg, Modic endplate changes) and discogenic pain (eg, disc degeneration and annular fissures). More advanced methods, like ultra-short-echo time imaging, and quantitative MRI further amplify MRI's accuracy in the detection of painful endplate and disc pathology. This review explores the pathophysiology of vertebrogenic and discogenic pain as well as the impact of different imaging modalities in the diagnosis of low back pain. We hope this information can help identify patients who may benefit from personalized clinical treatment and image-guided therapies.

[Modern aspects to the diagnosis and non-surgical treatment of low back pain]. / Sovremennye podkhody k diagnostike i nekhirurgicheskomu lecheniyu boli v nizhnei chasti spiny.

Low back pain is one of the most common complaints in primary care. This pain is usually nonspecific and musculoskeletal. However, identification and exclusion of specific causes of pain as early as possible are important for specialists since their underestimation can sometimes lead to life-threatening consequences. The authors analyze literature data on the key facts of anamnesis («red flags¼), management of patients with low back pain with emphasis on modern concepts and recommendations for diagnostics, identifying the dominant nature and cause of pain, differential diagnosis, and diagnostic significance of neuroimaging. Special attention is paid to existing options for conservative (drug and non-drug therapy) and interventional treatment methods, which have become increasingly popular in recent years.

Predictive Factors Associated with Chronic Neck Pain in Patients with Cervical Degenerative Disease: A Retrospective Cohort Study.

Purpose: To explore the predictive factors of neck pain (NP) in patients with cervical degenerative disease by retrospectively analyzing their occupational and demographic characteristics and to provide a valuable reference for preventing and treating chronic NP. Patients and Methods: We retrospectively reviewed the occupational and demographic data of patients with cervical degenerative disease who had undergone anterior cervical surgery between June 2021 and December 2022 at our center. The patients were divided into NP and no-NP groups based on whether they had chronic NP before surgery. Relevant occupational and demographic data from all patients were statistically analyzed, and all variables were made categorical. Forward stepwise logistic regression models were constructed for preoperative chronic neck pain to explore the possible risk factors associated with chronic neck pain. Results: The differences in smoking, being an office worker, BMI, and disease types between NP and no-NP groups were statistically significant. In contrast, there were no statistically significant in age, sex, academic level, duration, and degeneration grade between the two groups. Moreover, further logistic regression analysis indicated that smoking, being an office worker, having an abnormal BMI, and cervical spondylotic radiculopathy (CSR) were related to chronic neck pain. Conclusion: The present study indicated that smoking, being an office worker, having an abnormal BMI, and CSR were predisposing risk factors for NP associated with cervical degenerative disease. Although intervertebral disc degeneration is the pathology basis of NP, the degeneration grade was not related to the occurrence of NP in our current study. Therefore, quitting smoking, avoiding sedentariness, and maintaining a normal BMI may prevent NP to some extent.

Ultrasound-guided disc pain induction test for diagnosis of discogenic lumbar pain: a cross-sectional study.

BACKGROUND: Several methods can be used to diagnose discogenic pain, but only discoblock can diagnose discogenic pain definitively. This study aimed to examine the usefulness of an ultrasound-guided disc pain induction test for a simple and accurate diagnosis of the culprit lesion. METHODS: We included 41 patients with lumbar pain in whom pain was induced by an ultrasound-guided disc pain induction test. All patients had confirmed pain at L1/2 to L5/S1 based on an ultrasound-guided disc pain induction test and underwent X-ray photography and magnetic resonance imaging. Seventeen patients who required injection due to severe pain underwent discoblock procedures for discs with the most intense pain, and visual analogue scale (VAS) scores were obtained before and after the procedure for these patients. We analysed the association between painful discs and radiological findings. RESULTS: Pain induction was noted in a total of 65 discs, and the pain was induced in 23 patients in only one disc. All patients had disc degeneration of Pfirrmann classification grade 1 or higher, with more significant disc degeneration in painful discs than in painless discs. There was no significant relationship between the presence or absence of pain and Modic type. The average VAS measurements improved significantly from 9.5 (pre-procedure) to 2.5 (post-procedure). These results suggest that the most painful discs were the causes of discogenic lumbar pain. CONCLUSIONS: Our ultrasound-guided disc pain induction test may help diagnose disc degeneration and identify culprit lesions, even when multiple discs exhibit findings of degeneration.

Systematic Review of Platelet-Rich Plasma for Low Back Pain.

BACKGROUND: Low back pain (LBP) has a high economic burden and is strongly related to the degenerative process of the spine, especially in the intervertebral disc and of the facet joints. Numerous treatment modalities have been proposed for the management of LBP, and the use of platelet-rich plasma (PRP) has emerged as an innovative therapeutic option for degenerative disease of the spine. The present study aims to evaluate the efficacy of PRP injections in managing low back pain. METHODS: We conducted a systematic review in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) recommendations, a registered at PROSPERO Systematic Reviews Platform, under number CRD42021268491. The PubMed, Web of Science, and Scopus databases were searched to identify relevant articles, along with hand searching to identify gray literature articles, with no language restrictions. Randomized clinical trials (RCTs), nonrandomized trials (NRTs), and case series (CSs) with more than 10 patients were considered eligible. The quality assessment and the risk of bias of the randomized clinical trials were evaluated using the RoB II tool. An evaluation of the description of the preparation methods was performed using an adapted version of the MIBO checklist. RESULTS: An electronic database search resulted in 2324 articles, and after the exclusion of noneligible articles, 13 RCTs and 27 NRTs or CSs were analyzed. Of the 13 RCTs, 11 found favorable results in comparison to the control group in pain and disability, one showed no superiority to the control group, and one was discontinued because of the lack of therapeutic effect at eight-week evaluation. Description of the PRP preparation techniques were found in almost all papers. The overall risk of bias was considered high in 2 papers and low in 11. An adapted MIBO checklist showed a 72.7% compliance rate in the selected areas. CONCLUSIONS: In this systematic review, we analyzed articles from English, Spanish and Russian language, from large databases and grey literature. PRP was in general an effective and safe treatment for degenerative LPB. Positive results were found in almost studies, a small number of adverse events were related, the risk of bias of the RCTs was low. Based on the evaluation of the included studies, we graded as level II the quality of the evidence supporting the use of PRP in LBP. Large-scale, multicenter RCTs are still needed to confirm these findings.

Mesenchymal stem cells can improve discogenic pain in patients with intervertebral disc degeneration: a systematic review and meta-analysis.

Background: The meta-analysis aimed to estimate the efficacy of mesenchymal stem cells on lumbar discogenic pain in patients with intervertebral disc degeneration. Methods: A comprehensive literature search was conducted in the PubMed, Web of Science, Embase and Cochrane Library databases with predetermined search strategy up to 18 September 2022. The clinical studies focusing on evaluating the efficacy and safety of mesenchymal stem cells in patients with intervertebral disc degeneration were identified. The primary outcomes were changes of pain score and Oswestry Disability Index. The Newcastle-Ottawa Scale for cohort studies was used for quality assessment. Review Manager was used to conduct the statistical analysis. Pooled risk ratios were calculated based on the random effect model. Heterogeneity, subgroup, and publication bias analyses were also performed. Results: There were 2,392 studies were identified in the initial search, and 9 eligible studies with 245 patients were eventually included in this review. The Visual Analogue Scale score was significantly lower in patients after receiving mesenchymal stem cells therapy (mean difference = 41.62; 95% confidence interval 24.32 to 58.93; Heterogeneity: I2 = 98%; p < 0.01). And the pooled mean difference of Oswestry Disability Index was 22.04 from baseline to final follow-up points (95% confidence interval 8.75 to 35.33; p = 0.001; Heterogeneity: I2 = 98%; p < 0.001). The pooled reoperation proportion was 0.074 (95% confidence interval 0.009 to 0.175; Heterogeneity: I2 = 72%; p < 0.01). There were no serious related adverse events associated with the therapy. Conclusion: The findings of this meta-analysis indicated that mesenchymal stem cells therapy may be effective in relieving pain and improving Oswestry Disability Index significantly in patients with lumbar discogenic pain. Mesenchymal stem cells therapy may also be associated with a lower risk of adverse events and reoperation rates.

Minimally invasive interventional therapy for pain.

Pain interventional therapy, known as the most promising medical technology in the 21st century, refers to clinical treatment technology based on neuroanatomy, neuroimaging, and nerve block technology to treat pain diseases. Compared with traditional destructive surgery, interventional pain therapy is considered a better and more economical choice of treatment. In recent years, a variety of minimally invasive pain interventional therapy techniques, such as neuroregulation, spinal cord electrical stimulation, intervertebral disc ablation, and intrasheath drug infusion systems, have provided effective solutions for the treatment of patients with post-herpetic neuralgia, complex regional pain syndrome, cervical/lumbar disc herniation, and refractory cancer pain.

Multiplex epigenome editing of ion channel expression in nociceptive neurons abolished degenerative IVD-conditioned media-induced mechanical sensitivity.

Background: Low back pain is a major contributor to disability worldwide and generates a tremendous socioeconomic impact. The degenerative intervertebral disc (IVD) has been hypothesized to contribute to discogenic pain by sensitizing nociceptive neurons innervating the disc to stimuli that is nonpainful in healthy patients. Previously, we demonstrated the ability of degenerative IVDs to sensitize neurons to mechanical stimuli; however, elucidation of degenerative IVDs discogenic pain mechanisms is required to develop therapeutic strategies that directly target these mechanisms. Aims: In this study, we utilized CRISPR epigenome editing of nociceptive neurons to identify mechanisms of degenerative IVD-induced changes to mechanical nociception and demonstrated the ability of multiplex CRISPR epigenome editing of nociceptive neurons to modulate inflammation-induced mechanical nociception. Methods and Results: Utilizing an in vitro model, we demonstrated degenerative IVD-produced IL-6-induced increases in nociceptive neuron activity in response to mechanical stimuli, mediated by TRPA1, ASIC3, and Piezo2 ion channel activity. Once these ion channels were identified as mediators of degenerative IVD-induced mechanical nociception, we developed singleplex and multiplex CRISPR epigenome editing vectors that modulate endogenous expression of TRPA1, ASIC3, and Piezo2 via targeted gene promoter histone methylation. When delivered to nociceptive neurons, the multiplex CRISPR epigenome editing vectors abolished degenerative IVD-induced mechanical nociception while preserving nonpathologic neuron activity. Conclusion: This work demonstrates the potential of multiplex CRISPR epigenome editing as a highly targeted gene-based neuromodulation strategy for the treatment of discogenic pain, specifically; and, for the treatment of inflammatory chronic pain conditions, more broadly.

Assessment of a Discogenic Pain Animal Model Induced by Applying Continuous Shear Force to Intervertebral Discs.

BACKGROUND: Chronic discogenic pain includes degeneration-driven changes under the mechanical macroenvironment of an internal disc, which leads to the progressive changes of biochemical microenvironment that induce abnormal ingrowth of the nociceptor. The propriety of the animal model reflecting the pathologic natural history has not been assessed. OBJECTIVES: This study investigated the biochemical evidence of chronic discogenic pain by employing a discogenic pain animal model induced by shear force. STUDY DESIGN: Animal study utilizing rats in vivo model of a shear force device. METHODS: Fifteen rats were divided into 3 groups (n = 5/group) according to the period for which sustained dorsoventral shear force was applied (1 week or 2 weeks); the control group received the spinous attachment unit, without a spring. Pain data were collected using von Frey hairs on the hind paws. Growth factor and cytokine abundance was analyzed in the dorsal root ganglion (DRG) and plasma. RESULTS: After the shear force devices were installed, the significant variables were found to markedly increase in the DRG tissues of the 2-week group; however, they were not altered in the 1-week group. Specifically, interleukin (IL)-6, neurogrowth factor (NGF), transforming growth factor (TGF)-alpha, platelet-derived growth factor (PDGF)-beta, and vascular endothelial growth factor (VEGF) were increased. Meanwhile, the plasma levels of tumor necrosis factor-alpha, IL-1beta, IL-5, IL-6, IL-12, and NGF were increased in the 1-week group; whereas, TGF-alpha, PDGF-beta, and VEGF were increased in the 2-week group. LIMITATIONS: The limitations include the general limitations of quadrupedal animals, the poor precision and flexural deformation of shear force devices, inaccuracies regarding the evaluation of histological denaturation, and short intervention and observational periods. CONCLUSIONS: This animal model effectively generated biochemical responses to shear loading with evidence of neurological changes induced without direct macrodamage to the outer annulus fibrosus. Chemical internals were induced by mechanical externals among the contributing factors of chronic discogenic pain.