The mean pain intensity for inpatient consultations, for example in cancer patients, is known. However, the proportion of necessary consultations in the total volume of patients of a ward or a hospital, the general pain intensity in a surgical ward and the relationship between pain medication, length of stay and therapeutic success are unknown. The aim of the study was to examine surgical patients in a single normal ward subclassified into various groups  during half a year with regard to their pain. For this purpose, the pain score (NAS) was recorded daily for each patient during the entire hospital stay and the change was assessed over the clinical course.In 2017, all consecutive new admissions to a normal ward of general surgery at a university hospital (“tertiary center”) were monitored over half a year according to a standardized procedure. Pain severity  from admission to discharge was recorded, as well as the length of stay and the administered medication. Patient groups were sub-classified as surgery, intensive care unit, cancer and pain consultation. An algorithm in two parts , which was defined years before between surgeons and pain therapists, was pursued and consequently used as a basis for the evaluation of the therapeutic success.269 patients were included in the study. The mean pain intensity of all patients at admission was VAS 2.2. Most of the groups , non-OP, pain intensity greater than VAS 3) were significantly reduced in pain at discharge. An exception in this context was patients with cancer-associated pain and, thus, initiated pain consultation.“cancer”, 11.1 ± 9.4 d; mean“consulation”, 14.2 ± 10.3 d). Twenty-one consultation patients, in whom it had been intended to improve pain intensity, could not be successfully treated despite adapted therapy – this can be considered a consequence of the low number of patients. Since the consultation patients were the only patient group treated with part 2 of the algorithm, it can be concluded that part 1 of the algorithm is sufficient for a mean length of stay up to 9 days. For all patients above this time point, a pain consultation with adaption of medical treatment should be considered.Since three quarters of the consultation patients also reported cancer pain, it might be possible that the lack of treatment success in both the consultation and cancer groups is associated with cancer in these patients. However, it can be shown that the successfully treated groups (without ICU-based course) had a mean length of stay from 4.2 ± 3.9 up to 8.4 ± 8.1 days (d), while the two unsuccessfully treated groups experienced a longer stay (mean In surgery, pre-, intra- and post-operative pain management forms the basis for greater patient satisfaction and can be helpful in avoiding pain-associated sequelae and complications . NeverthIn a US study from 2011, less than 50 % of patients with postoperative pain received adequate pain therapy [In 2017, the pain outpatient clinic of the University of Magdeburg investigated the quality of analgesic administration in consults using the example of cancer patients. Weaknesses were identified in 375 patients.Hardly any slow-release opioids were given prior to the pain consultation. The non-retarded opioids were given only when needed and only subcutaneously or intravenously. Co-analgesics were hardly used .In the pain outpatient clinic at the University Hospital of Magdeburg (Germany), a therapeutic algorithm has been developed in interdisciplinary cooperation with surgeons and inaugurated to clinical practice to optimize pain therapy . The algIn a recent publication, Stramer et al. found that after major surgery and prolonged pain, NSAIDs may be administered safely for longer than three days .Additionally, more than 300 pain-associated consultations in cancer patients over 3 years were evaluated in a retrospective study. Therein, despite relatively high pain scores (mean VAS 5.5), successful pain therapy – by using the second part of the algorithm – was achieved in 70 %  of cases .The substantial disadvantage of that approach and, in addition, of many other studies was that only consultations were considered, documented and evaluated. No data exist for the proportion of pain consults on a normal ward of general surgery. In addition, there is no reliable value known for the general pain level on a general surgery ward. Furthermore, no data was available on how many patients the described algorithm was applied to.What is the level of pain on a typical general surgery ward?Was it possible to achieve sufficient pain reduction in patients from admission until discharge?Were there any special features with regard to the success of pain therapy in certain sub-classified groups of patients?(a)Do the pain consultations reflect the clinical reality of pain reported on a surgical ward?(b)How can patients who were brought to a pain-associated consultation be characterized?Pain consultations:Are the recommendations of the pain therapy algorithm of the university of Magdeburg realistic, and how long can the first part of the algorithm (NSAID plus unretarded opioids) be applied?Therefore, the following questions were raised:Standardized continuous observation of all patients in a university general surgery ward over a longer period of time provides clarity about the level of pain in the ward, the proportion of pain consults required and the medications needed for successful pain management. Most patients have a pain intensity of VAS≥4. Nevertheless, successful pain therapy using retarded opioids is possible in most patients. In about 10 % of cases, pain consultations become necessary.The Study was approved by the ethics committee of the University Hospital Magdeburg.A prospective questionnaire study was conducted on ward 1 of the Department of General, Abdominal, Vascular and Transplant Surgery of the University Hospital at Magdeburg (Germany) during the time period from 01/01/2017 to 06/30/2017.All medical and nursing staff of the ward were informed about the data collection before the start of the study period.At the beginning of a hospital stay, the nursing staff handed out a standardized questionnaire see  for the During the entire inpatient stay, the nursing staff recorded the patients’ pain intensity twice a day using the “visual analogue scale” (VAS) and recorded the values in the ward’s documentation system. This pain recording was conducted in conjunction with the daily blood pressure, pulse and body temperature checks.If a patient had to be transferred to the intensive care unit (ICU) of the university hospital during the hospital stay, the daily VAS values were not recorded during these ICU days. The recording of pain scores was continued when the patient was transferred back to the normal ward. If a patient was transferred to another ward of the hospital, this was regarded as a discharge, the data recording was terminated and it was regarded as a new admission in the event of a possible transfer back.The pain intensity (VAS) was taken subsequently from the inpatient documentation system.The starting data relevant to pain therapy were taken from the questionnaire handed out by the nursing staff at the beginning of the hospital stay. This included pain localization, pain intensity, onset, course, rhythm and any factors influencing the pain, concomitant symptoms, pain medication and pain quality.The pain medication at the beginning and in the course of the clinical stay was also taken from this documentation system. Pain medication was recorded under assignment to the subgroups antipyretics (NSAIDs), weak opioids, strong opioids and psychotropic drugs.Other data relevant to this study were found in the patient records and the patients’ medical letters. These included the diagnosis, whether a surgical intervention had taken place, the day of surgery and the length of stay. Length of stay was subdivided into preoperative, postoperative, total and ICU days spent at the university hospital.–Head/neck, – Gastrointestinal tract,–Hepatobiliary system, – Other abdominal organs,–Lymphatic system, – Skin/bone/connective tissue and–Other(s).The diagnoses treated were assigned to different headings, which in turn were based on specific body regions. The generic terms are:Furthermore, the date of discharge, any malignancy present (equated with the term “cancer diagnosis” in this study) were extracted from the patient records and letters.For data collection, the documentation system of the outpatient clinic (Pain Division) was also used and provided information about consultations and medication changes by the pain therapists.January 2017 was used as trial month. Patients who had been admitted to the ward during the period from 01/01/2017 to 01/31/2017 were, therefore, not subsequently included in the scientific evaluation.Furthermore, the scientific evaluation did not include individuals for whom the diagnosis was still unknown and who had been admitted to the inpatient unit exclusively for a non-interventional, non-surgical diagnostic procedure.Patients from other wards or medical disciplines, who were temporarily housed on surgical ward 1 due to a shortage of beds, were also not included in the analysis.®) for breakthrough pain prior to surgery and for a maximum of the first three post-operative days. The epidural catheter was not considered in the evaluation.Patients undergoing major abdominal surgery at the University Hospital of Magdeburg usually receive an epidural catheter with i.v. or s.c. piritramide .As a result, patients were provided with an information sheet and informed consent form at the beginning of their inpatient stay, in addition to the pain management admission form. This information sheet see , Part 1 With the informed consent form see , Part 2,They consented to the pseudonymized data collection and were additionally informed that revocation of consent is possible at any time without giving reasons.The questionnaire used see  was give–Pain localization–Pain intensity–Pain quality–Previous course of pain–Concomitant symptoms–Current pain medication with dosage and time of intake.The parameters collected in the questionnaire were:The visual analogue scale (VAS), respectively, numeric rating scale (NRS), in the field of pain therapy is actually a range of semiquantitative values extending from zero to ten. VAS 0 was defined as “no pain” and VAS 10 as “pain intensity at which the patient would jump out of the window”.In addition, for comparability with international literature, pain was classified as mild (VAS 1–3), moderate (VAS 4–6) and severe (VAS 7–10).® SPSS Statistics, version 24  was used for statistical data collection and analysis.The software IBMFirst, a descriptive description of the study variables was performed. Special interest was given to diagnosis, pain quality, pain medication and pain intensity. Results were reported as frequencies in absolute and percentage terms and as position and ratio parameters .The Wilcoxon paired difference test was used to compare pain levels at admission and discharge . Comparisons of pain severity and other quantitative data regarding different subgroups were made using the Mann–Whitney U test. Contingency table analyses were performed to show associations between qualitative variables, using Pearson’s chi-square test.A probability of error of α=0.05 was assumed as the significance level for the statistical tests.The study was conducted in accordance with the guidelines of the 1964 Declaration of Helsinki for Biomedical Research of the “World Medical Association” and its further implementing regulations as well as on the basis of “Good Clinical Practice” and “Good Research Practice”.Of the original 568 patients enrolled during the study period, only 269 could be included in the study at the end for final and reliable analysis see .The general patient data are presented in The subgroups, the pain intensity and the length of stay are presented in One third of the patients did not undergo surgery.Most patients experienced no ICU stay despite surgery. Out of the 193 operated patients, only 51 (26.4 %) were admitted to the ICU.Most subgroups studied had mean pain intensity below VAS 3.Non-cancer patients had significantly higher pain intensity scores on admission than cancer patients (p<0.001).Of the 193 operated patients, pain levels were assessed in 160 patients on the day after surgery. Among these, 32 reported no pain. Post-operatively, the majority of patients had mild  and moderate  pain. Only 10 patients (6.4 %) had severe pain during post-operative course.Pain level on admission is higher in non-cancer patients than in cancer patients (2.6 + 2.9 vs. 1.3 + 2.3).A significant pain reduction was achieved in patients with mild pain in the following groups: Total group, patients with and without ICU stay, patients without cancer, patients with and without surgery.p=0.238), and in the 95 cancer patients (1.3 ± 2.3 vs. 1.1 ± 1.6).The mean pain intensity from admission to discharge was not reduced in 21 pain consults,  with moderate pain (4.9 ± 0.8 vs. 1.8 ± 1.9).There were 30 patients with severe pain at the time point of admission. The pain reduction at discharge was reduced .Patients successfully treated (outside ICU) had shorter lengths of stay than those unsuccessfully treated:Length of stay in patients without operation was 4.2 ± 3.9 and in the operated patients 8.4 ± 8.1 days.p>0.001) (cancer patients vs. Operated patients: p=0.01).In cancer patients 11.1 ± 9.4 and in non-cancer patients: 5.0 ± 4.9 days (In the 21 pain consults 14.2 ± 10.3 days (consultation patients vs. operated patients: p<0.005).In comparison, the length of stay of the two unsuccessfully treated groups was:The exception to this is the successfully treated ICU patients with a length of stay of 14.8 ± 8.1 days.At the beginning of the study period, the mean pain intensity of the consultation patients was 2.6 and could not be reduced up until discharge.cancer patients and a significantly longer hospital stay than the overall group, while patients with VAS≥4 had the lowest proportion of cancer patients and the shortest length of stay of these three groups (patients VAS≥4 vs. consultation patients: p<0.001).Patients who received a pain consult form a special group. They had a significantly higher proportion of All patients outside the consultation group did not receive sustained-release opioids but received unretained piritramide.–Specifically:239/269 Patients (88.85 %) received a WHO level 1 medication after admission; 200/269 (74.35 %) received piritramide (unretarded piritramide i.v.) or opioid s.c.Patients without surgery received antipyretics in 71.1 % and a strong opioid (piritramide) in 39.5 % during the stay.More than two-thirds of patients received an unretarded strong opioid in the following groups:A total of 95.9 % of patients with surgery received antipyretics and 88.1 % piritramide during the clinical course whereas 93.0 % of patients with VAS≥4 received antipyretics and 73.0 % piritramide.The patients with ICU stay received antipyretic in 93 % and a strong opioid in 84 % of cases.The fundamentally different medication of the therapy algorithm , part2 wThe consultation patients received sustained-release opioids (morphine sulfate) in 95.2 % – and (despite discontinuation in the consultation) continued to receive antipyretics in 95.2 %. Only 18 patients received psychotropic drugs. These were prescribed in context of the pain therapy consultations.“Not only does inadequate pain management following surgery result in increased morbidity and mortality, but it also may delay recovery, result in unanticipated readmissions, decrease patient satisfaction and lead to chronic persistent postsurgical pain .” The meAs late as 1998, Neugebauer et al.  found thAt the University Hospital of Magdeburg, this issue was specifically addressed by first developing an algorithm for anesthesiologists. In 2008, the first manual on pain therapy suitable for a lab coat pocket was published. It was intended to help the pain therapy consultant to treat pain according to a certain basic pattern. This was followed by the creation of an extended algorithm mentioned above, which also defined the actions to be taken by the primary treating surgeons during the first days after surgery but still before a possible consultation .Previous work on postoperative pain has varied widely in design. In 2004, Strohbuecker et al.  studied In a multicenter study of 3,251 patients, Maier et al.  found thThe aim of the present study was to examine the population of patients in a single surgical ward during half a year with regard to their pain. For this purpose, the pain score (VAS) was recorded daily for each patient during the entire inpatient stay.It is first important to note that 51.3 % of patients in the studied ward reported no pain on admission.–Low pain levelsAccording to the “German Pain Society”, patient-reported VAS≥4 is defined as pain and >6 as severe pain ; VAS <4 VAS 2.2). This was true not only for the ICU patients but also for the cancer patients. This corresponds to the values found by Maier et al. [Almost all groups studied  reported mild pain during hospital stay , more than twice as high as in the total group. However, in our own study   and moderate (35 %) pain post-operatively. Only 6.4 % had severe post-operative pain. Thus, 40 % of patients had moderate to severe pain post-operatively. This is slightly higher than the German study from 2010 but lower than the Austrian values from 2017 , up to 3In the algorithm of the University Hospital of Magdeburg, there are two stages: Therapy of the first three days and therapy during the following days . During In a US study from 2011 , 80 % suA total of 239 of 269 (88.8 %) patients in the present study received a WHO level 1 drug after admission, and 200/269 (74.3 %) received (unretarded) strong opioids.However, the medications given were within the algorithm already published elsewhere : piritraCancer patients did not receive sufficient pain therapy due to a lack of prescribed sustained-release opioid (in the context of a consultation). A total of 95 patients with a tumor lesion were treated on the surgical ward. Therefor, 80 cancer patients did not get a pain consult at all to optimize pain treatment. The question of why could not be satisfyingly answered.Only 7.8 % of patients were prescribed sustained-release opioids – these were the 21 pain consults.Only 18 patients (6.7 %) received psychotropic drugs according to part two of the algorithm in the further course. These patients were also exclusively from the consultation group.In its entirety, the pain therapy on the investigated ward corresponds to the algorithm agreed upon between pain therapists and surgeons .Only in 21/289 patients 7.8 %), a pain-consultation was requested by the ward. Thus, the consultation rate for pain patients is higher than other consultation rates in the CL (consultation-liaison) literature from psychiatry and palliative care. It is known from psychiatric literature that while 40 % of patients in German hospitals have a mental disorder, only 2.5 % receive a consult . It is k.8 %, a pIn addition, it is interesting to note that, despite discontinuation of antipyretics by the consultant, subsequent data processing revealed that these were nevertheless continued to be given as requested by the nursing staff.According to Surgical patients with a mean hospital stay of up to 8 days could successfully be treated for pain with part one of the algorithm (NSAIDs with piritramide).In a recently published recommendation by the German Pain Society, the German Society of Anesthesiology and Intensive Care Medicine and the German Society of Surgery, the authors suggested that NSAIDs may be taken for longer than three days postoperatively for persistent pain .Although antipyretics were discontinued by the pain therapist in the consults . It could not be clarified why retarded opioids were not used outside the consults.The ICU stay was not part of this investigation. The patients with stay on ICU were not evaluated as equivalent to the other subgroups because they were not continuously under the observed pain therapy on the normal ward. Therefore, it cannot be clarified how the ICU patients could be successfully reduced in pain despite a longer duration of stay of >9 days.It was not recorded how long piritramide and antipyretics  were given during the stay on the normal ward. However, based on the experience obtained in the evaluation of cancer consults , it mustThe reasons for a pain therapy consultation could not be deduced. Possibly, the consultation request had an association with the length of hospital stay of the patients . There is no algorithm for pain consults to date.Despite cooperation with the nursing staff, the pain intensity was inquired postoperatively only in 169 of the 193 operated patients (87.6 %). In this context, a study by McDonald et al. is interesting :–Not wanting to complain,–Not wanting to take the provider away from other patients,–Avoiding unpleasant analgesic side effects (and)–Not wanting to take drugs.“The majority described avoiding or delaying communicating their pain at some point during their hospitalization. Reasons for decreased pain communication included:Postoperative patients may be unclear about their role in pain management.”With the agreed algorithm, pain reduction was achievable in 174 non-cancer patients (64.7 % of the 269 patients studied). This was true for mild as well as moderate to severe pain. Sustained-release opioids and psychotropic drugs were not necessary for therapeutic success at short duration.A pain consult should be considered if the patient is treated for pain for more than 9 days as a change in medication to sustained-release opioids and psychotropic drugs must be considered.Increased attention should be paid to establishing a pain consult in cancer patients. The administration of antipyretics or medication on demand has not yet been clearly established.For the first part of the therapy algorithm, adding a tolerance limit up to a 9 days post operatively to the duration of therapy with NSAIDs and nonretarded opioid seems feasible.Why patients with an ICU stay were still successfully treatable despite a long length of stay requires further research.Supplementary MaterialClick here for additional data file.


Pain is a frequent problem among hemodialysis patients, mostly caused by painful procedures, acute complications of hemodialysis, and painful syndromes, such as musculoskeletal and neuropathic syndromes. Pain can frequently lead to sleep disturbances, reduced adherence to hemodialysis treatment, frequent hospital admissions, decreased quality of life, and high mortality rates. Non-pharmacological management of pain in the hemodialysis population includes aerobic and resistance exercises, music therapy, and cognitive behavioral therapy. The present review focuses on the factors affecting pain in hemodialysis and its non-pharmacological management, offering important information to renal professionals. Pain is a common problem among patients on hemodialysis, with incidence ranging from 8 to 82% . It is mMuscle cramps are mostly caused by hypotension due to excessive fluid removal during hemodialysis and electrolyte disturbances . SimilarIn a study with 300 patients on hemodialysis, it was found that pain had a significant association with patients’ comorbidities and increased body mass index. It can be assumed that comorbidities usually increase pain, while obesity possibly deteriorates chronic pain by reducing the pain threshold and increasing its sensitivity . SimilarPain can negatively affect the mental health of dialysis patients  and can Musculoskeletal pain in hemodialysisRenal bone disease is a frequent problem in hemodialysis which is usually caused by disorders in calcium-phosphate metabolism, lack of vitamin D, and uremic toxins . Hsu et Additionally, comorbid diseases such as ischemic peripheral artery disease, diabetic neuropathy, and osteopenia/osteoporosis frequently lead to different types of musculoskeletal pain . In a stAdditionally, long-term dialysis is related to amyloidosis because amyloid deposition occurs in musculoskeletal structures which clinically manifests as destructive arthropathy, erosive spondyloarthropathy, and bone cysts . In a siMoreover, Molsted and Eidemak  found inRestless leg syndromeRestless leg syndrome is a disturbance of the central nervous system, wherein patients have the necessity to move their legs or other parts of their body while sleeping. A common symptom of restless leg syndrome is pain in the calves and legs, especially when the legs are inactive . The maiPain during fistula cannulationAbout 20% of patients on hemodialysis have serious pain during cannulation, despite the use of analgesics topically . About 4Additionally, in patients with cardiovascular diseases, cardiac complications are significantly increased during and after the surgery for the creation of vascular access due to anxiety because anxiety raises heart and respiratory rates, cardiac output, and oxygen requirements . In theiNon-pharmacological management of pain in hemodialysisEffective management of pain in renal patients includes management of pain related to fistula puncture, aerobic and resistance exercises, music therapy, and cognitive behavioral therapy. Additionally, good sleeping conditions, reduction of the use of alcohol and caffeine, and kidney transplantation can lead to a reduction of symptoms of restless leg syndrome . HoweverAerobic ExercisesAerobic exercises improve the quality of life and reduce mortality rates in dialysis patients . RegularIt has been found that aerobic exercises reduce different inflammatory cytokines and improve oxidative stress in patients with chronic kidney disease . In a siMusic TherapyIt has been found that music therapy can significantly decrease pain and anxiety during dialysis therapy  and is eSimilarly, in a study with 65 dialysis patients, it was shown that participants who were listening to music during vascular access surgery had significantly lower perceived levels of pain than the control group . In a siWhen people listen to their desired music, it helps them reduce the feeling of pain possibly because music affects the autonomic nervous system and leads to emotional and physiological improvement . Music tThus, music therapy is a safe and cheap method, with no side effects of pharmacological therapy, and can be easily applied to reduce pain and anxiety during fistula punctures .Cognitive Behavioral TherapyPain is not only a sensory but also an emotional experience . CognitiPain is a frequent problem among dialysis patients. Pain can frequently lead to sleep disturbances and reduced adherence to hemodialysis treatment, frequent hospital admissions, decreased quality of life, and high mortality rates. Non-pharmacological management of pain in the renal population includes management of pain related to fistula cannulation, aerobic and resistance exercises, music therapy, and cognitive behavioral therapy. However, complex pain syndromes need analgesic drugs tailored to the needs of each patient.


Intraosseous basivertebral nerve ablation has shown sustained efficacy in treating chronic axial low back pain (LBP) in patients with type 1 or 2 Modic changes. This systematic review aims to determine the efficacy of intraosseous basivertebral nerve radiofrequency ablation in treating nonradiating axial chronic LBP compared to standard therapy, sham, or without contrast. The population of interest is individuals greater than or equal to 18 years old with chronic nonradiating vertebrogenic pain. The key outcome was the percentage of patients with greater than or equal to 50% pain reduction, greater than or equal to 10-point improvement in function and disability measured by the Oswestry Disability Index (ODI), greater than or equal to two-point pain reduction in the visual analog scale (VAS) or numerical pain rating scale, and a decrease in opioid utilization by 10 morphine milligram equivalents.Three databases, PubMed, MEDLINE, and Google Scholar, were used to retrieve the studies for the review. Two independent reviewers assessed the studies for inclusion using the validated tools for quality appraisal. There were 286 articles in total; however, only 11 publications with extensive data on 413 participants matched the inclusion criteria and were used for this review. At three months, a majority of the participants reported greater than or equal to 10-point improvement in the ODI, a measure of functional and disability improvement on a 10-point scale, and greater than or equal to two-point improvement in the VAS. A good number of patients in the basivertebral nerve ablation (BVNA) arm reported complete pain resolution demonstrating therapy success and the superiority of BVNA over sham and standard treatment. Basivertebral nerve radiofrequency ablation, among other criteria, is a safe and minimally invasive therapy that significantly lowers pain and impairment in individuals with vertebrogenic pain with distinct Modic type 1 and 2 changes at lumbar vertebra three-sacral vertebra one (L3-S1) vertebral levels. Proper patient selection and exact procedural methods are essential to the success of basivertebral nerve neurotomy. The findings of the existing investigations require confirmation by nonindustry-funded, large-scale, high-quality trials using generalizable study participants. Chronic low back pain (CLBP) or vertebrogenic pain is one of the debilitating conditions frequently encountered in pain management. CLBP is a low back pain (LBP) lasting more than six months. It is one of the most common causes of disability, absenteeism from work, and excessive consumption of healthcare resources worldwide -11. The About 30% of the population in the United States has LBP, with approximately 50 million physician visits yearly . In the PathophysiologyCLBP is multifactorial and can be discogenic or axial, radiating or nonradiating, and specific, or nonspecific. Despite the innovations and progress in medical diagnosis, about 80% to 90% of LBP are nonspecific, resulting in a lack of clarity in treatment modalities with an associated mixed outcome. This is because of the multidimensional nature of LBP and the complexity of pinpointing the pain generator . The treCLBP can result from nociceptive signals originating from spinal and paraspinal structures. The annulus fibrosis, the outer layer, and the nucleus pulposus, the inner layer, are the two separate layers that make up the intervertebral disc. The hypersensitive nociceptors of the degenerating intervertebral disc, which originate from the annulus fibrosis, were once thought to be responsible for transmitting pain (annulogenic pain). Despite this, current research has demonstrated that the vertebral body endplate contributes significantly to the pathologic innervation linked to disc degeneration and transmits pain signals via the basivertebral nerve (BVN) (vertebrogenic pain) ,4,17,18.The endplate comprises cartilage and bone, separating the intervertebral disc from the adjoining vertebrae . The carThe pathophysiology of the Modic endplate alterations that cause vertebrogenic discomfort has undergone significant advancement. Current evidence has shown that cytokines play a role in the development of MCs. Degenerating disc contiguous to MCs produces high levels of cytokines and osteoclastic factors, which control the composition of adjoining bone marrow and change bone mass . Toll-liModic modifications can be of three types: vertebral endplate disruption, fissuring, degeneration, and active inflammation are all examples of type 1 MCs -11. TheyMoreover, the density of BVN in damaged endplates is higher when compared to nondamaged endplates confirming the link between BVN and CLBP. Patients with CLBP associated with MCs present with increased frequency and duration of LBP and worse outcomes with conservative therapies and after discectomy. This group of patients is more likely to seek medical care, unlike patients with LBP without MCs ,5,17,20.Diagnosis and managementThe diagnosis and management of vertebrogenic pain are challenging. Due to the high rate of false positives, provocative discography, which was once utilized to diagnose discogenic pain, is today debatable. The increase in LBP that patients experience following discography may be explained by the knowledge that discography promotes endplate deflection, which amplifies the release of nociceptors and causes pain ,4,5. MRICurrent evidence shows that basivertebral nerve ablation (BVNA), a minimally invasive procedure, is safe and effective in managing CLBP in patients with type 1 and type 2 MCs on MRI . A recenObjectives and rationaleThis systematic review aimed to examine the most recent research on the safety, efficacy, adverse effects, and complications of BVN radiofrequency ablation in managing vertebrogenic pain in patients with MCs. Numerous research studies have been published about the effectiveness of BVN radiofrequency ablation, which the Food and Drug Administration (FDA) has approved for treating vertebrogenic discomfort with type 1 and type 2 MCs at lumbar vertebra three (L3) through sacral vertebra one (S1) vertebral levels . MethodThe identification, selection, evaluation, and synthesis of the studies used in this systematic review were conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines to ensure transparency, accuracy, and comprehensiveness of the review . SpecifiThe primary outcome of interest was greater than or equal to (≥) 50% pain reduction in the visual analog scale (VAS) or numerical pain rating scale (NRS). The secondary outcomes include ≥10-point improvement in function in the Oswestry disability index (ODI), greater than or equal to two-point pain reduction in the NRS, mean reduction in the NRS, VAS, and ODI, and decreased or discontinuation of opioid intake, and improvement in the quality of life. There is no restriction on the duration of the studies and the outcomes. The studies included for review were prospective randomized controlled trials, including double-blinded, single-blinded, open-label, single-arm trials, narrative reviews, systematic reviews, and meta-analyses. Reports, letters to editors, book chapters, case studies, expert opinions, studies conducted outside the United States and Canada, studies written in languages other than English, manuscripts, studies with quality assessment less than 70% on validated scales, and studies older than five years were excluded. The clinical studies that evaluated the effectiveness of intraosseous BVN rhizotomy for the treatment of CLBP in patients with evidence of MCs on the MRI were obtained by searching PubMed using the medical subject headings (MeSH) strategy, MEDLINE, and Google Scholar. The searches were completed on June 23, 2022. Some studies were extracted from the cited references of the included publications. The search strategies and results are shown in Table Study selectionThe publications were independently evaluated for inclusion by two authors with formal training in evidence-based medicine and quality research using the validated quality appraisal tools. Studies are included for review if they satisfy the following criteria: studies with relevant information on intraosseous BVN neurotomy for the treatment of CLBP with MCs, those conducted with appropriate methodology and procedural technique, those that analyzed and reported data using authenticated metrics and tools, and those that clearly reported the outcome of interest, risks, and complications related to the treatment. Data items and collectionThe following information was taken from the studies: bibliographic data such as the authors and year of publication, study designs, the setting in which the studies were conducted, participant selection methods, descriptions of the procedures and techniques, and other procedural reports, as well as details about author disclosures such as study funding and conflicts of interest, outcomes measures for pain reduction, and improvement in disability and function.Assessment of risk of bias and methodology of the studyIn order to ensure that the participants in the studies were representative of the target population, a rigorous methodologic evaluation was conducted to evaluate the quality of the research using validated techniques and the patient selection process. Other factors evaluated include using validated tools for outcome measurement, use of a control group, less than 20% attrition rate, and conflicts of interest on the part of the authors. The body of evidence from each study was evaluated using the suggested quality rating tools. The duration and results of the research were not restricted because BVN RFA is an innovative treatment.ResultThe literature search and screening were conducted following the PRISMA guidelines, as shown in Figure Prospective randomized control studiesIn 2018, Fischgrund et al. published the result of a prospective multicenter randomized sham-controlled double-blinded clinical trial on 225 patients comparing BVN RFA to sham treatment . The objoC) for 15 minutes under image guidance targeting the terminus of the BVN at about 40% to 60% of the posterior to the anterior distance across the vertebral body. In the sham arm, the exact same procedure was followed, with the exception of docking the introducer cannula to stimulate radiofrequency ablation (RFA) for the same amount of time. At six weeks and six months, the patients were observed. The patients in the sham arm were allowed to cross over at one year. The ODI and the Medical Outcomes Trust Short-Form Health Survey (SF-36) were used to evaluate the disability and functional outcomes, and the VAS was used to assess back pain. The patients had MRI at six weeks and six months of follow-up to evaluate MCs. Both the patients and the physicians who conducted the follow-ups were blinded. The safety endpoints were the incidence and severity of adverse events (AEs).Patients were randomized 2:1 to either the treatment or the sham arm. Of the 225 patients, 147 were assigned to the treatment arm and 78 to the sham treatment, 113 received general anesthesia, and 112 received moderate conscious sedation. The patients in the treatment arm received transpedicular bipolar BVN RFA at 85 degrees Celsius  and per protocol populations was done in accordance with the FDA-approved protocol (PP). The targeting success was determined by the overlap of the RFA zone and the terminus of the BVN at the treated zone, evidenced on MRI at the six-week follow-up. Targeting success was observed in 89% (129 out of 145 patients) of the treated patients and 94.6%  of the treated vertebrae. The vertebrae treated were L3-S1 vertebrae. Targeting failure was observed in 16 patients; one was excluded for procedural failure, and two were excluded for protocol noncompliance in the RFA arm. Only one patient was excluded from the sham arm due to protocol noncompliance. In the RFA arm, the follow-ups at three, six, and 12 months were 98.7%, 98.2%, and 96.9%, respectively, and 98.7%, 97.4%, and 97.4% for the sham arm. Before the three-month evaluation, six patients exited the study, two withdrew their consent, three were removed after undergoing an invasive spinal procedure, and one died before the 12-month visit due to reasons unrelated to the study. At the three-month follow-up, the difference in ODI improvement between the two groups was statistically significant  less than (<).05), with 19.0 least squares mean (LSM) in the treatment group compared to 15.4 LSM in the sham group. The treatment group in the ITT and PP populations had 19.0 LSM and 20.5 LSM, respectively. The sham group had an ODI improvement of 20.5 LSM in the ITT group and 15.2 LSM in PP populations (p<.05).However, the improvement in the ODI between the groups at six and 12 months was not statistically significant (p greater than (>).05). When a 10-point improvement in the ODI was utilized, 75.6% of patients in the treatment arm and 55.3% in the sham arm had a successful response. Referencing the target VAS of greater than 4 cm, the improvement in VAS among the two groups was not statistically significant at three months. The LSM improvement in VAS was 2.97 in the RFA group compared to 2.36 in the sham group (p >.05); the improvement in VAS at six and 12 months was statistically significant, 3.04 cm compared to 2.08 cm (p<.05) at six-month; and 2.84 cm in the RFA arm versus 2.08 cm in the sham arm (p<.05) at 12 months with a minimally clinically significant difference (MCID) for VAS of 1.5 cm. The change from baseline in the physical component of SF-36 in the PP for the RFA and the sham arm were not statistically significant at three, six, and 12 months. The MCID was 4.9. However, for the mental component of SF-36, the change from baseline in the PP group in both the treatment group and the sham arm was not significant at three and six months but was at 12 months (p<.05).At one year, 73% (57 out of 78) of patients in the sham group were permitted to cross over to the RFA group, and data were collected only at three months. The high rate of crossover led to the conversion of the randomized clinical trial (RCT) to a nonblinded single arm intrapatient comparison in the BVN RFA arm at one year to minimize bias. AEs included one device-related event (sham group) and eight procedure-related events in six patients (two from the sham group). These AEs include nerve root injury in one patient in the sham arm, two cases of lumbar radiculopathy, retroperitoneal hemorrhage in one patient, and four transient motor or sensory deficits on the femoral nerve. The difference in the AEs between the two groups was insignificant, and all the cases were resolved. At six-week and six-month follow-ups, MRI did not demonstrate any spinal cord abnormalities, accelerated disc degeneration, or avascular necrosis except for a single case of a change from Modic type 1 to type 2. The researchers received industry funding.In 2019, Fischgrund et al. published 24-month outcomes of the Sequential Multiple Assignment Randomized Trial (SMART) [The mean of the physical component summary (PCS) score of the SF-36 improved from 42.83 at 12 months to 45.83 at 24 months, demonstrating the effectiveness of BVN RFA in the treatment of vertebrogenic LBP. The analysis of the baseline characteristics of the 106 patients treated at 24 months demonstrated that 68 patients had LBP for over five years, 28 were on opioids, and 61 had prior spinal injections. However, at 24 months, only eight treated patients received spinal injections for continuing or new onset LBP. Opioid usage at two years was not assessed due to irregularity of visits on the part of the patients, but at 12 months, 60.7% of the patients had a decrease in opioid usage, and 46.4% stopped opioid use. At one year, two patients treated with RFA had surgical spine interventions, one had lumbar fusion at the treated levels, and one microdiscectomy at lumbar vertebrae two-three (L2-3) level above the indexed levels due to new disc herniation. Additional seven RFA patients had a lumbar fusion at the RFA levels. There were no reported late complications. The study was industry-funded.In 2020, Fischgrund et al. published five-year outcomes on the SMART Trial targeting the 117 patients who were successfully treated out of the 133 patients that underwent the treatment in the per-protocol population from the original trial . HoweverIn 2020, Markman et al. published outcome data on a one-year post hoc analysis of the SMART Trial on opioid use . In thisPragmatic studiesIn 2019, Khalil et al. published the outcome of a multicenter prospective, randomized, open-label clinical trial on 140 patients with vertebrogenic CLBP comparing BVN ablation with standard care  . Among toC under image guidance targeting the terminal of the BVN at approximately 30%-50% across the sagittal vertebral body width. In contrast, the patients in the standard care arm continued treatment with spinal injections, pain medications, exercise, physical therapy, acupuncture, and chiropractic management. The primary endpoint of the trial was set at three-month follow-up, and the prespecified provisional analysis for superiority assessment was conducted when 60% of the participants completed a three-month follow-up. The patients in the BVN RFA group were followed at six weeks then three, six, nine, 12, and 24 months postoperatively. SC patients were observed at three, six, nine, and 12 months. For this study, the functional impact was measured with the ODI, the VAS was used for LBP, and SF-36 and European quality of life five dimensions (EQ-5D-5L) were used to measure Health Status and Quality of Life, respectively. The baseline ODI was 46.1, the VAS was 6.67, and the percentage of patients with CLBP for greater than five years was 67.3% and 70% had tried standard care. About 70% of the patients had received spinal injections and 16% had prior RF ablation of a facet or sacroiliac joint(s). RFA for BVN or SC was randomly assigned to each patient in a 1:1 ratio. The participants in the treatment arm received unilateral transpedicular intraosseous BVN RFA to any four vertebrae in a nonconsecutive approach for 15 minutes at 85The primary outcome was a mean change in ODI, VAS, SF-36, and EQ-5D-5L scores from baseline. The study outcomes were analyzed with the intent to treat. At a three-month follow-up, the independent data management committee (DMC) recommended halting the enrollment in the study and offering patients in the standard care arm early crossover treatment to the BVN RFA arm due to the shown statistical superiority of the BVN RFA treatment over standard care on the prespecified outcomes (p<.001). The independent DMC also ruled out any safety concerns with the BVN RFA treatment. All 51 RFA patients completed treatment, 40 received two-vertebral bodies, and 11 received three vertebral bodies treatment, with lumbar vertebra five to sacral vertebra one (L5-S1) being the most frequently treated, followed by lumbar vertebra four to lumbar vertebra five (L4-L5) and lumbar vertebra four to sacral vertebra one (L4-S1). The mean duration of the procedure was 92.5 minutes. Patients in the standard arm received a spinal injection prior to the three-month endpoint, but none in the RFA arm. There was no significant difference in opioid reduction at three months among the two treatment groups. At the three-month follow-up, the RFA arm reported a 25.3-point : -29.6 to -21.0; p<.001) decrease in the ODI from baseline compared to a 4.4-point  decrease in the standard treatment arm. There was a 74.5% clinical success in the RFA arm compared to 32.7% of patients in the control group. In the RFA group, 62.7% reported greater or equal to 20 points improvement in the ODI compared to 13.5% in SC patients (p<.001). The RFA arm demonstrated a 3.46-point  decrease in the VAS from baseline compared to a 1.02-point  reduction in the standard arm; 2 cm improvement threshold was 72.5% of patients in the RFA arm compared with 34.0% of patients in the SC arm. The mental and physical components of SF-36 mental for RFA and SC were 2.615  versus −2.786 ; and 14.021  versus 2.114  respectively. The change from baseline in EQ-5D-5L was 0.1803  in the RFA arm compared with 0.0135  in the standard care arm, all favoring BVN RFA treatment. Among the 51 patients treated with RFA, 39 reported 78% improvement, eight had no change, and three patients reported worsened condition. The targeting success was observed in 96% (49 out of 51 patients) of the treated patients and 98%  of the treated vertebrae, and only two patients had target failure. Altogether, 22 AEs were observed; 15 were observed in 13 patients treated with RFA, including incisional pain, urinary retention, lateral femoral cutaneous neurapraxia, leg pain, and mild paresthesia, which resolved before the three-month follow-up. In 2021, Smuck et al. published the outcome of a prospective randomized multicenter open-label Trial on 140 patients with vertebrogenic CLBP comparing BVNA with standard care . This trAt six months, the difference in the reported outcomes was statistically significant, favoring the BVNA group. At the six-month follow-up, 67.2% of the patients reported a greater than or equal to 15-point reduction in ODI (p<.001) compared to 12.5% in the SC arm and a greater than or equal to 2 cm reduction in VAS in 58.3% of patients versus 6.0% in the SC arm (p<.001). There was no change in terms of chronic opioid use. At six months, 67.2% of the patients reported a greater than or equal to 15-point reduction in the ODI (p<.001) compared to 12.5% in the SC arm and a greater than or equal to 2 cm reduction in VAS in 58.3% of patients versus 6.0% in the SC arm (p<.001). There was no change in terms of chronic opioid use. At three and six months, the patients in the SC who were allowed to crossover to BVNA treatment had significant improvement in pain relief and function. There were a 24.7-point reduction in ODI from baseline at three months and a 25.9-point reduction at six months. The patients reported a 3.5 cm reduction in VAS at three months and a 3.8 cm decrease at six months. Among the treated patients, 65% reported a greater than or equal to 50% decrease in VAS, 36.2% reported a greater than 75% reduction, and 22.4% reported 100% pain relief six months post BVNA. Quality of life increased significantly from baseline in all patients treated with BVNA both at six and 12 months. At 12 months post-RFA, there was a 25.7-point mean reduction in ODI (p<0.001) and a 3.8-point reduction in VAS. In the BVNA arm, 64% of patients experienced a greater than or equal to 50% reduction in VAS, 44.3% attained a greater than 75% reduction, 29.5% of the patients achieved 100% pain relief, 68.9% had a greater than or equal to 15 points improvement in ODI, while 60.7% had a greater than or equal to 20 points improved ODI. The SF-36 and EQ-5D-5L improved significantly in one year.Before the 12 months visit, 54.5% of patients in the BVNA arm received epidural steroid injections (ESI). At 12 months after BVNA, 4.5% received ESI of the same region versus 18.0% in the SC arm. Patients in the SC arm who received BVNA did not receive ESI at six months follow-up. At 12 months, 74% of patients in the BVNA arm reported improved pain relief, and 75% had treatment success. The patients in the SC arm who received BVNA reported 78% improvement and 72% treatment success at six months. Patient satisfaction and quality of life measured with SF-36 and EQ-5D-5L improved substantially. Following the 12-month follow-up visit, four patients reported postoperative leg pain secondary to the length of the procedure and positioning. Of the 127 patients treated with BVNA, 13 reported nonserious transient leg pain deemed device-procedure-related and resolved within 43 days. Other AEs included one case of urinary retention, one case of nausea, one case of skin rash due to prep solution, one case of corneal abrasion from surgical eye protection, and one case of infection to the incision site. No device-related severe AEs were reported during the 12-month visit. The study was industry-funded. In 2021, Koreckij et al. published the 24-month outcomes of the Intracept Trial [At two years, 77.2% of the patients reported a greater than or equal to 15-point reduction in the ODI (p<.001), a greater than or equal to 20-point reduction in 68.4% of patients (p<.005), and a greater than or equal to 2 cm reduction in VAS in 79% of patients. There were also significant improvements in SF-36 PSC and EQ-5D-5L. Following the 24-month follow-up visit, seven out of the 58 patients received ESI compared to 29 before the 24-month enrollment, a 76% reduction; three of the post-RFA ESI were at the BVNA treated levels. In the BVN RFA arm, 11 patients were on opioids at 24 months compared to 21 at baseline, a 62% reduction in active opioid use from baseline. In the BVNA arm, five patients out of 66 treated had spinal procedures performed at the treated levels at 24 months. Target success was observed in 72% of the BVNA patients without spinal injections post BVNA. At the two-year follow-up, in the BVNA arm, 79% of the treated patients reported improvement in the baseline condition, 21% had no change, 71% reported returning to enjoying pre-LBP activities, and 84% will repeat the procedure if needed. In the BVNA group, 11% reported nonserious device-procedure-related mild transient leg pain, and 12 out of the 13 AEs were related to pedicle breach. No device-related severe AEs were reported during the 24-month visit. The study was industry-funded. oC under image guidance targeting the terminal of the BVN. Among the 48 patients treated, only 47 were successful. In 2020, Macadaeg et al. published the result of one-year outcome data of a prospective, single-arm study on 48 patients investigating the effectiveness of intraosseous BVNA for the treatment of LBP . Of the At the 12-month visit, only 45 patients followed up. The baseline ODI at 12 months was 47.13, the VAS was 6.82, 72.3% of the patients had a greater than or equal to five years of LBP, 75% were employed full-time, 21% had 2.5 days of work absenteeism due to LBP, 48.9% had received lumbar ESI, and 21.3% were on opioid. The targeting success was achieved in 96% of the treated patients and 98% of the treated vertebrae. The trial was performed on an intent-to-treat protocol. There was a significant improvement in pain and function from three months to 12 months post-BVN RFA. At 12 months post-BVN ablation, 89% of patients reported a greater than or equal to 15-point improvement in the ODI, and 84.44% reported a greater than or equal to 20-point improvement in the ODI from baseline (p < .001). There was remarkable improvement in the VAS, almost double the established MCID. At 12 months, more than 68% of the treated patients reported pain reduction greater than or equal to 50%; 51% of patients reported a greater than or equal to 75% decrease in pain, and 38% reported complete pain resolution. At 12 months post-BVNA, patients reported improved quality of life, as noted in the remarkable improvement in SF-36 and EQ-5D-5L. At 12 months post-BVNA, one patient had ESI for foraminal stenosis compared to 23 at baseline, one patient had facet ablation, and three patients were taking opioids compared to 10 at baseline, a 70% reduction. At one-year post-BVN ablation, 84.4% of the patients reported improved condition, 11% had no change, 4.0% had worsened symptoms, and only three missed work for two days. At 12 months, three nonserious device procedure-related events were reported; one was an aborted procedure due to inability to access the pedicle, and two were potential pedicle breaches resulting in radiculitis, which resolved after treatment with oral medications.Meta-analysisIn 2022, Conger et al. published a single-arm meta-analysis on the effectiveness of intraosseous RFA of BVN in CLBP patients . The metIn this single-arm meta-analysis, the target success rate for 50% pain reduction at six and 12 months was 65%  and 64% , respectively. At six and 12 months, the ODI improvement rates of 15 points were 75% (95% CI 63-86%) and 75% (95% CI 63-85%), respectively. The authors also performed an ITT analysis of the success rate, which showed that 61% (95% CI 48-74%), 59% (95% CI 40-77%), 49% (95% CI 43-56%), and 50% (95% CI 41-58%) of participants reported a greater than or equal to 50% pain improvement at six, 12, 24, and 60 months, respectively. At six, 12, 24, and 60 months, the improvement in the ODI of a greater than or equal to 50-points was 71% (95% CI 59-82%), 70% (95% CI 57-81%), 57% (95% CI 50-64%), and 57% (95% CI 49-65%), respectively. The authors maintained that there is some evidence that BVNA reduces pain and disability in people with persistent LBP.Systematic reviewIn 2021, Conger et al. published a systematic review (SR) of four publications assessing the quality of current evidence on the safety, efficacy, and complications of BVN RFA for CLBP [The studies selected for the review included RCTs, nonrandomized comparative studies, and single-group observational studies. The excluded studies were case reports, expert opinions, and manuscripts in a non-English language. The publications were obtained from MEDLINE and Embase. The search yielded 725 publications that were screened for duplicates and eligibility; seven studies were selected that met the inclusion criteria, and a total of four articles with detailed outcomes of 321 participants were reviewed. Two independent authors assessed the studies for inclusion using validated screening criteria, and the third independent author reviewed the studies for discrepancies. Studies were included if they presented information on the efficacy or effectiveness of intraosseous BVN radiofrequency neurotomy (RFN) for the management of CLBP, appropriate procedural information, rigorous study methodology, data analysis based on evidence-based medicine (EBM), and complications associated with BVN RFA.The reviewers assessed the studies for methodologic rigor, risk of bias, and quality of evidence with the Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) appraisal system. Seven publications were included in this systematic review. According to the authors of this SR, there is moderate-quality evidence supporting the effectiveness of BVN RFN for treating CLBP in patients with MCs in MRI using the GRADE measurement. Compared to standard care treatment or sham procedures, there is moderate-quality evidence that BVN RFN is more effective at lowering pain and impairment in carefully selected patients with CLBP. In patients with targeting failure, BVN RFN had minor to no measures of success over the sham procedure. The authors recommended high-quality non-industry-funded studies to confirm the outcomes of the studies.Narrative reviewIn 2021, Tieppo et al. published the result of a narrative review on the effectiveness, safety, and rationale of basivertebral nerve ablation in the management of vertebrogenic LBP . The datThe authors concluded that BNV RFA is effective in managing patients with chronic vertebrogenic LBP lasting for at least six months with MCs type 1 or type 2 on MRI between L3-S1 spinal segments and who had failed conservative treatment for at least six months. Based on the reviewed articles, there was evidence that BVN RFA is more advantageous than standard care in treating CLBP. According to the authors, BVN RFA has a statistically significant benefit in pain reduction, quality of life improvement, opioid use reduction, and functional improvement. There were no severe adverse events, or device-related death observed. They concluded that BVN RFA is a safe and effective procedure for managing vertebrogenic pain using the correct procedural technique in an appropriate patient population. The generalizability of the study was a concern for the authors as the majority of the participants in the studies were Caucasians. There was an issue with all the studies being industry-funded. There was a recommendation to conduct a non-industry-funded research with a more representative patient population. This literature review was industry-funded. Table DiscussionThis systematic review aimed to evaluate the quality of evidence of the current published studies on the effectiveness, efficacy, safety, and complications associated with intraosseous BVN RFA for treating CLBP. Following the criteria outlined in established guidelines, a total of 11 studies with detailed outcomes of 413 participants with CLBP were selected and reviewed . The oriTo date, conservative and invasive procedures to manage CLBP with MCs have not demonstrated durable improvement in disability and function. These include pharmacological and non-pharmacological strategies, including surgery following the World Health Organization's stepladder approach to managing chronic pain . EpiduraTransforaminal and interlaminar endoscopic lumbar RFA have also been used to treat discogenic pain in patients with degenerative intervertebral disc or spinal stenosis due to disc protrusion ,30. CurrThe BVN RFA was compared to sham treatment in the SMART trial and SC in the Intracept trial. These studies provided strong evidence supporting the vertebral endplate as the source of CLBP and BVN as a crucial player in transmitting pain signals in patients with CLBP. The studies evaluated in this review showed that individuals with axial persistent LBP of vertebral etiology, with MCs type 1 or type 2 on L3-S1 lumbar segments, who have failed conservative treatments for at least six months and satisfy other criteria, can benefit from BVN RFA. In all the studies, functional outcomes were measured with ODI, improvement in pain with VAS, and quality of life was evaluated using the short form SF-36 and the EQ-5D-5L questionnaire.Other outcomes assessed were patient satisfaction and reduction in opioid utilization. The data from the studies showed that in patients in the BVN RFA arm, the mean ODI decreased by more than twice the MCID. The targeting success, described as an overlap between the ablation zone created by RFA and the terminus of the BVN at each treated level, ranged from 89% to 100% of the treated patients confirmed by post-ablation MRI results at six months . Lack ofIn the SMART trial, the two groups observed the same protocol. The sham surgical procedure involved docking the introducer cannula 1-2 mm into the pedicle to stimulate the RFA with an equivalent dwell time as the BVNA without turning on the RF device. At the three-month follow-up, the BVN RFN failed to outperform sham treatment, without a statistically significant difference in the ODI between the two groups. At an ODI of greater than or equal to (≥) 15-point improvement, the BVNA did not significantly outperform the sham procedure with 59% (95% CI: 51-68%) versus 49% (95% CI: 37-60%) reported outcomes, respectively. In interpreting these outcomes, it is crucial to note that the outcome of a surgical treatment is a cumulative effect of the critical surgical element, placebo effects, and non-specific effects, which may have played a role in this study . TherefoThe authors failed to report the follow-up outcomes in the ODI between the two groups at six- and 12-month follow-ups. The prior systematic review conducted by Conger et al. obtained these results by contacting the authors [Though at six and 12 months, there were improvements in the ODI in both groups, the difference between the groups was not significant. The mean improvement in the ODI at the 24 months and at five years follow-up of the SMART trial was 53.7% (p<.001) and 60.6% (p<.001), respectively. A sustained improvement was also observed in pain reduction and quality of life. The trials found that BVN RFN was a safe, durable treatment for vertebrogenic pain with MCs, showing maintained clinical benefits in the ODI for the treatment arm at two-year and five-year post-treatment follow-up.In the study by Khalil et al., BVNA was compared to SC . The SC However, the inadequate quantifiability of the standard treatment made it difficult to express what BVNA treatment outperformed and posed a challenge in interpreting the results of this study. Prior studies have shown that poor descriptions of the SC in an RCT may alter the interpretation of the outcomes . But theA similar result was reported in the study conducted by Macadeg et al. in patients with similar characteristics as the SMART trial . HoweverThe one-year post hoc analysis of the SMART trial observed the effect of BVNA on opioid utilization as a secondary outcome. At 12 months, patients who decreased opioid use before BVNA had remarkable improvement in the ODI and VAS and better pain relief than those with increased opioid use in the treatment and sham arms (p<.001). These findings showed an association between reduction in opioid use and functional benefits from BVNA. At the five-year follow-up in the SMART trial, 34% of patients were using opiates at baseline, and 22% completely stopped opiates by the five-year follow-up. The study by Markman et al. is the only one that solely focused on the correlation of opiate use and BVNA with improvement in function and pain as a primary outcome . The stuThe single-arm meta-analysis by Conger et al. showed moderate evidence supporting the effectiveness of BVNA in treating vertebrogenic pain with clinically significant improvement in pain and function at six months (65%) and 12 months (75%) after BVNA . It alsoPost-SMART studies have reported targeting success rates greater than 95%, proving that successful BVN neurotomy can be achieved frequently with established techniques . TherefoThe inclusion and exclusion criteria were based on the findings from prior research. The strictness of the inclusion and exclusion criteria made it challenging to generalize the research findings in this review. For instance, the inclusion of only patients with CLBP for greater than six months, isolated lumbar pain, lack of response to conservative treatment for at least six months (nonoperative management), and MCs Type 1 or Type 2 at L3-S1 levels. Additionally, a minimum ODI of 30  and a minimum VAS of 4 cm  were required. In addition to the exclusion of patients with radicular pain, previous lumbar spine surgery, symptomatic spinal stenosis, osteoporosis (with T score 2.5), disc extrusion or protrusion greater than (>) 5 mm, spondylolisthesis > 2 mm at any level, and other spinal etiologies, patients with obesity and depression, and MCs at different levels, not L3-S1. It is worth noting that eligibility is crucial in any study because it protects the study participants and explains the target population for the study, but the extreme narrowness of the inclusion criteria can affect both the study result and generalizability ,39. HoweIn terms of AEs, BVNA has proven to be safe. In all the studies, the AEs were relatively rare. The reported adverse events included nonserious and self-limited events such as nerve root injury (one patient), lumbar radiculopathy (two cases), retroperitoneal hemorrhage (one patient), and transient motor or sensory deficits on the femoral nerve (four patients). There were no spinal cord abnormalities, accelerated disc degeneration, or avascular necrosis on the post-BVNA MRI performed at six-week and six-month follow-ups. Other reported minor AEs included incisional pain, urinary retention, nausea, skin rash due to prep solution, transient leg pain, and mild paresthesia, which resolved before the three-month follow-up. There was one corneal abrasion from surgical eye protection, one case of infection at the incision site, and one aborted procedure due to the inability to access the pedicle with resultant transient radiculitis. No device-related severe AEs were reported during the 12-month visit. When BVN RFA becomes a routine procedure, other AEs and complications may be observed.Also, large-scale studies may be essential in unveiling other AEs and complications not observed in these studies. BVN RFA remains an effective treatment for CLBP with Modic type 1 and type 2 changes. In the clinical studies, the independent data management committee recommended halting the enrollment and offered early crossover for patients in the control arm due to the compelling interim analysis result, which is unusual for the low back treatment study. The high success rate is attributable to selecting a well-defined subpopulation of patients with CLBP and a well-defined and precise technique. The randomization in the studies was successful, but the attrition observed was not significant (<1%); however, the authors did not explicitly report how it was accounted for during data analysis. It might affect the outcomes because attrition affects the ability to perform a full intention-to-treat analysis, which can lead to bias. In randomized trials, such attrition can substantially impact the strength of the research findings .Another factor that may affect the generalizability of the studies was the demographic races of the participants. While the participants in Fischgrund (91.2%) and Khalil et al. 93.3%) were predominantly Caucasians .3% were ,5,17, MaHeterogenous study participants improve the generalizability of clinical results and eliminate bias and skewness of the result of a clinical trial. Lack of diversity in clinical studies is not only a generalizability issue but also a moral, scientific, and medical issue. Thus, diversifying clinical trial participants is needed to help ensure that the trial population is representative of the patients who will use the medicinal product . The autIt is worthwhile noting that the degenerative changes in the endplate noted in MRI were observed both in symptomatic and nonsymptomatic patients. Some patients with degenerative disc disease develop MCs while others do not. The pathophysiology behind this remains unclear. The review of a cross-sectional magnetic resonance imaging study showed that the endplate defects have a similar distribution pattern as MCs in the lumbar spine. Endplate defects were associated with MCs, decreased disc signal intensity, disc height loss, and increased disc bulging ,43. TherAdditionally, all the studies reviewed were industry-funded except the systematic review by Conger et al., increasing reporting and publication bias due to an inherent conflict of interest which may hinder the publication of negative results ,2,44. InMany factors contributed to the strength of this review, such as the use of methodologic quality appraisal tools to evaluate the studies for inclusion. The review was designed and completed following the recommended quality and reporting guidelines unique to the systematic review. The review was executed following PRISMA and assessment of multiple systematic reviews-2 (AMSTAR-2) guidelines ,45,46. ALimitationsThe absence of grey literature is a limitation of the present review. Meta-analysis was not performed because of the novelty of the intervention and the scarcity of RCTs. The studies selected for the review were only free full-text studies with free access conducted in the United States and Canada within the last five years, retrieved from three databases MEDLINE, PubMed, and Google Scholar; all non-English language studies were excluded.BVN RFA is a safe and minimally invasive novel procedure for treating CLBP in patients with Modic type 1 and type 2 changes on L3-S1 vertebral levels. It is recommended in patients with CLBP lasting at least six months who have failed to respond to conservative treatment, including pharmacological and nonpharmacological therapies. The current studies have shown consistent evidence supporting the effectiveness and durability of BVN RFA in reducing pain and disability and improving function in CLBP patients for at least three months and longer. Evidence also proves that BVN RFA is superior to sham and standard care in managing CLBP patients.The review provided evidence showing that BVN RFA has clinically significant benefits in a reduction in pain and disability, opioid reduction, and improvement in quality of life and function in patients with vertebrogenic pain with distinct Modic type 1 and 2 changes. The review also showed that BVN RFA is a safe procedure with few transient adverse events. There were no device-related deaths or serious AEs in reviewed studies. Additionally, nonindustry-funded large-scale, high-quality trials with generalizable study participants are needed to confirm the results of the current studies and further assess the AEs and complications. BVNA appears to be a safe and effective intervention for patients with vertebrogenic pain when proper patient selection and precise procedural techniques are employed.


Pain is one of the most persistent symptoms after cancer treatment. The central nervous system can erroneously stay in its alarm phase, altering the pain experience of patients who have cancer. Pain neuroscience education (PNE) with multimodal approaches may benefit these patients.This protocol aims to determine the effectiveness of a PNE tool on pain, physical function and quality of life, as a supplement to a multimodal rehabilitation (MR) program in patients who had breast cancer (BC).An 8-week double-blinded randomized controlled trial will be conducted, including 72 participants who had BC and who have persistent pain, randomized into three groups: PNE program + MR program, traditional biomedical information + MR program and control group. The PNE program will include educational content that participants will learn through a mobile app and the MR program will include a concurrent exercise program and manual therapy. The primary outcome will be the perceived pain assessed using the Visual Analogue Scale and secondary outcomes are others related to pain, physical function and quality of life. All outcomes will be evaluated at baseline, at the end of the intervention and 6 months after the end of intervention.The proposed study may help BC patients with persistent pain improve their pain experience, quality of life and provide for more adaptive pain-coping strategies. This protocol could propose an action guide to implement different integral approaches for the treatment of sequelae. This treatment option could be offered to this patient profile and it could be easily implemented in the healthcare systems due to its low costs.NCT04877860. .ClinicalTrials.gov,  Despite the increasing incidence , more anThe main therapeutic agents in cancer are chemotherapy, targeted therapy, immunotherapy, hormonal therapy, surgery, and radiotherapy. Chemotherapy may induce peripheral neuropathy causing neuropathic pain persisting for weeks or years post treatment . AdditioCentral sensitization (CS) as a new diagnosis label , is ofteManual therapy may have immediate effect on cancer pain and may improve physical function . PhysicaEducational interventions on pain management have mostly centered on traditional biomedical information (TBI), analgesics and explanations of perceived pain were based on tissue issues . The recPNE has previously been used in the physiotherapy management of breast cancer patients with controversial results. Giving PNE instead of biomedical education can be more effective in reducing CS-related symptoms, pain catastrophizing, pain intensity, and pain interference . HoweverSome previous proposals have monitored and implemented therapeutic recommendations with mobile apps in health problems of high prevalence and high cost to our society, such as hip fractures  or the iThe main aim is to study the short- and long-term effects of a PNE tool as a supplement to a multimodal rehabilitation (MR) program in BC patients with persistent pain upon finishing adjuvant treatment to determine its impact on pain, physical function and quality of life. Our hypothesis is that a PNE tool as a supplement to a MR program based on exercise and manual therapy techniques, will be more effective in improving persistent pain in cancer patients than an MR program combined with TBI. This will be compared to a control group.0), at the end of the 8-week intervention (t1) and 6 months after the end of the intervention (t2). Assessments will be performed in 1 session of approximately 2 hours or two different sessions of 1 hour each.The protocol has been developed following the recommendations of the SPIRIT checklist. The study was approved by the Ethics Committee of the Junta de Andalucía (2205-N-20) in concordance with the Declaration of Helsinki. The PaiNEd trial was registered with ClinicalTrials.gov. ID: NCT04877860. A parallel three-arm superiority randomized controlled trial with assessors and data analyzers blinded to the interventions will be performed. Patients will be assessed at three different times, following the recommendations of the SPIRIT checklist and diagram : baselinhttp://csaludable.ugr.es/pages/dossierultimo/%21), a cancer rehabilitation research unit of the Mixed University Sport and Health Institute, University of Granada.Participants will be randomized into three arms . It willThe inclusion and exclusion criteria for eligible participants of the study are detailed in Upon completion of the recruitment process, participants will be randomized (ratio 1:1) into each of the groups using a random number generation program . Assessors and data analyzers will be blinded to the randomization of the participants. The blinding of assessors will be guaranteed by the fact that some members of the research group will perform first assessments and others will perform the post-treatment and follow-up assessments.The estimation of the sample size and statistical power for the trial were determined based on the main variable, pain measured through the VAS. Based on a previous study  and estiThe PaiNEd study will consist of 24 sessions lasting 8 weeks. The first intervention group will receive the PNE program and MR program. The second group will receive the MR program and TBI, provided in a pamphlet, on the management of pain and disability associated with side effects of cancer treatment. Finally, a control group will receive only the leaflet given to the second group.For 8 weeks, patients will attend 60 minutes of supervised exercise and one manual therapy session with a duration of 30 minutes every 2 weeks.This intervention group will attend the same multimodal group as the previous one, but without access to the PNE intervention and receiving TBI in a leaflet format.This group will only receive TBI on the management of pain and disability associated with side effects of cancer treatment handed in a leaflet format. Once the measures are registered, they will be invited to participate in the multimodal program for ethical and moral reasons.http://www.paininmotion.be) and ‘The Pain Toolkit’ [This modern PNE program is tailored to the pain needs of survivors of cancer, and the educational content is based on the book “Explain Pain” , the PaiToolkit’ . ParticiToolkit’  of the MThe MR program features supervised exercise and manual therapy. It will be fully supervised by a physiotherapist who specializes in the implementation of exercise programs and manual therapy in the oncological population and will be individualized to the needs and circumstances of the participants.Exercise. Patients will receive 3 nonconsecutive sessions per week at the CUIDATE unit, and the program will last 8 weeks. An overview of the exercise program is presented in Manual therapy. Participants will receive 1 manual therapy session every 2 weeks. Each session will last approximately 30 minutes. Treatment sessions will be developed based on previously published protocols that demonstrate effectiveness in treating pain and dysfunction in oncology patients [patients , 34. Thepatients .All participants will receive written and verbal informed consent and a signed copy of the consent form with the Principal Investigator’s contact details if they have more questions, previous to first assessment. Participants are informed that they can leave the study at any time without penalty or loss of benefits. Eligible participants will not suffer any potential harm in the study. There are no economic incentives for participating in the study. If significant changes regarding objectives, eligibility criteria, outcomes or interventions occur, a formal amendment to the protocol will be needed. Therefore, approval by the Ethics Committee of the Junta de Andalucía and the research team will be required. Clinical data will be taken from the electronic medical records by the participating health personnel. A questionnaire based on sociodemographic issues will be provided at the beginning of the assessment. Questionnaires are collected through the PaiNEd app.The visual analog scale (VAS), offers a subjective pain estimation. The VAS is a 100 mm straight line starting with 0 that represents “no pain” and ends with 100 representing “worst pain imaginable” . The VASPain catastrophizing. The Pain Catastrophizing Scale (PCS) is a self-administered scale of 13 items and one of the most used tools to assess catastrophizing in the face of pain. Patients take as a reference their past painful experiences and indicate the level to which they experienced each of the 13 thoughts or feelings in a Likert scale of 5 points that goes from 0 (never) to 4 . A total score is obtained from the scale that reflects the level of catastrophizing in the face of the patient’s pain. It contains 3 aspects: a) rumination (constant worry and inability to inhibit thoughts related to pain); b) magnification (the exaggeration of the unpleasantness of situations of pain and expectations of negative consequences), and c) helplessness (the inability to face painful situations). The values of the instrument range between 13 and 62, indicating low scores, low catastrophizing, and high values, high catastrophizing [ophizing . The PCSophizing .Central sensitization. The Central Sensitization Inventory (CSI) is composed of two different parts. The first one consists of 25 statements, each answer is scored: 0 Never, 1 Rarely, 2 Sometimes, 3 Often, and 4 Always. So that, at most we will be able to obtain a score of 100 and a minimum of 0. The second part is a survey in which patients explain if they have been diagnosed of specific disorders. Higher CSI scores mean greater symptoms of CS. If patients obtain a score greater than or equal to 40, we will consider that they have sufficient psychometrics to be correlated with CS syndromes [yndromes . The CSIyndromes .Kinesiophobia. Kinesiophobia will be measured by an 11-item version of the Tampa Scale of Kinesiophobia (TSK-11). Each item has 4 response options, “strongly disagree” scores 1 point, and “strongly agree” scores 4 points. The maximum possible score is 44 points and the minimum is 11 points. Greater scores mean strong fear of movement. The Spanish version showed good reliability and validity [validity .Quality of life. The European Organization for Research and Treatment of Cancer (EORTC). Created a general quality of life questionnaire known as EORTC–C30 [ORTC–C30 . It is aORTC–C30 . When anORTC–C30 .The QLQ BR-23 module for BC , consistLevel of physical activity. The International Physical Activity Questionnaire (IPAQ) is one of the most used generic physical activity (PA) questionnaires [onnaires . The shoonnaires . The PA onnaires . ICC = 0onnaires .Active Range of Motion (AROM). A plastic universal goniometer with two adjustable overlapping arms is used to objectively measure the active range of motion of the shoulder joint with the patient placed in the supine position [position . A cerviposition . AROM meposition . Cervicaposition .Functional capacity. The Six-Minute Walk Test (6MWT) determines the maximum distance (meters) that a person can walk in 6 minutes. The test take place in a 30-metre stretch of unimpeded walkway. Blood pressure, blood oxygen saturation and Borg’s modified Scale (0–10) of RPE are provided at the beginning and the end of the test. Heart rate is measured during the test. Patients are notified when each minute passes and standardized encouragement is given during the test [the test . The testhe test . Minimalthe test .Hand-grip strength. Grip strength is assessed with a manual dynamometer  [, Japan) . The tes, Japan) .Deep Neck Flexor (DNF) endurance. The DNF endurance test measures the endurance of the deep flexor muscles of the neck [the neck . It consthe neck .Body composition. Direct Segmental Multi-frequency Bioelectrical Impedance Analysis (DSM-BIA) is used for assessing skeletal muscle mass (Kg), fat mass (%) and body weight (kg). DSM-BIA is evaluated using the In-Body 720 body composition analyzer , following the instructions of the user’s manual [s manual . Patients manual  and 0.95s manual .Saliva will be collected in the morning period (09:00 to 11:30 a.m.) . The salTo enhance the retention of treatment groups, the app will show users when they come to the cancer rehabilitation research unit for assessments or multimodal treatment sessions, as well as how many weeks and sessions remain. Participants will also be notified of their assessment and treatment appointments by phone or e-mail according to their preferences.The mobile app will be installed in each patient’s mobile and instructions about how properly use it will be given. All data will be stored in accordance with the European General Data Protection Regulation.Only the researchers involved in the PaiNEd protocol will have physical access to all pseudoanonymized and encrypted information, with the server located at the University of Granada . This will ensure the safety of data management. Personal data will be handled in a way that they can no longer be attributed to study participants, following the principles of anonymity and confidentiality throughout the study.To analyze the results, the statistical program IBM SPSS 26  will be used. The descriptive statistics for this study  will use mean and standard deviation (continuous data) or frequencies and percentages . The Kolmogorov-Smirnov test will be applied to verify the normal distribution of the variables (p> 0.05). Receiver operating characteristic (ROC) curves will be included to determine the accuracy of the tests. A t test will be used to analyze parametric variables, and a Mann–Whitney U test will be used for nonparametric variables. From the point of view of inferential statistics and to respond to the main objective of this study, an intention-to-treat analysis will be carried out. A 3x3 repeated-measures ANOVA model will be performed using time  as a within-subject factor and intervention  as a between-subjects factor. The Bonferroni test will be used for post hoc analysis. For the study on subgroups with possible differential results, cancer location, type of treatment, elevated tumor stages, age, sex will be used as possible confounding variables in a subsequent multiple regression analysis. A significance level of p value less than 0.05 (P < .05) will be considered. The intergroup effect sizes will be calculated to provide magnitude changes; the effect size will be estimated using Cohen’s d .The current trial will determine if the application of combined PNE with an MR program presents higher efficacy in reducing pain than the application of this MR program without PNE. Previous studies have demonstrated that the combination of PNE with other therapies such as exercise or dry needling, obtains better results in kinesiophobia and pain than the sum of its parts in chronic neck pain , 66. TheDifferent studies have shown the efficacy of MR programs  in health issues related to pain and dysfunction associated with medical treatment of BC –72 or coAlthough participants can also have different levels of PA outside the program. It will be registered with the IPAQ-SF questionnaire and considered for analyses. Even though low adherence levels might be expected from the exercise program, supervision by the physical therapist and social interaction between participants will reinforce adherence and physical function. This could open up the possibility to participants to share their pain coping strategies and all achievements made. In addition, despite there will be participants who will not know how to use the app, they will be taught how to properly use it to benefit the most from PNE.The proposed study may help BC patients with persistent pain improve their pain experience, quality of life and provide for more adaptive pain-coping strategies. This protocol could propose an action guide to implement different integral approaches for the treatment of sequelae. If the group that includes PNE sessions proves to be more effective in reducing pain and improving physical function and quality of life than the groups without PNE, this treatment option could be offered to this patient profile and it could be easily implemented in the healthcare systems due to its low costs. Our results will be disseminated through social media, professional conferences and international refereed journals.We expect moderate effectiveness on pain, physical function and quality of life due to the multimodal approach and the fact that we give the PNE contents 6 months after having undergone surgery and/or have finished adjuvant treatment (radiotherapy and/or chemotherapy). Providing PNE in the early postoperative stage , could bResults from the PaiNEd trial will be disseminated in peer-reviewed journals, national and international conferences focused on pain, oncology and rehabilitation. Furthermore, findings will also be available through social media of the research team. Finally, participants and other interested cancer patients will know the final results of the study.S1 Checklist(PDF)Click here for additional data file.S2 Checklist(PDF)Click here for additional data file.S1 File(PDF)Click here for additional data file.S2 File(PDF)Click here for additional data file.