Lumbar spinal stenosis is a common degenerative disorder that is characterized by pain and neurogenic claudication. Previous studies have evaluated the effects of an epidural steroid injection (ESI) on spinal stenosis, based on changes to the spinal canal diameter.This study aimed to examine the impact of the ESI on pain scores and walking distance in patients with lumbar central spinal stenosis, stratified based on disease severity, which was graded according to the degree of cauda equina separation.We reviewed the medical records of patients who received the ESI for lumbar spinal central canal stenosis. A total of 128 patients were divided into moderate and severe groups, based on the degree of cauda equina separation.Relative to baseline values, 2 weeks after the ESI, the moderate group showed a significant decrease in the numeric rating scale (NRS) scores and an increase in walking distance. Meanwhile, the severe group showed a significant decrease in the NRS scores and no significant change in walking distance. The moderate group had lower NRS scores and a longer walking distance than did the severe group 2 weeks after the ESI. The proportion of patients with improved levels of satisfaction was higher in the moderate group than in the severe group.Lumbar interlaminar ESI may reduce pain scores and increase walking distance in patients with moderate lumbar spinal central canal stenosis. Patients with moderate spinal stenosis achieved better outcomes than did patients with severe stenosis. An epidural steroid injection (ESI) may be considered in patients whose condition does not improve with conservative care. While some studies have challenged the role of the ESI in pain reduction, functional improvement, and claudication in patients with lumbar SS,–6 other studies have suggested that the ESI may help relieve pain and improve functional outcomes in these patients.–9 Consequently, the effects of the ESI on lumbar SS remain subject to debate,–11 while the effectiveness of treatment for lumbar SS may vary depending on disease severity.Lumbar spinal stenosis (SS) is a common degenerative disorder that is characterized by pain and neurogenic claudication.,13 Previous studies have reported that the spinal canal dimension does not predict the success or failure of the ESI in patients with lumbar SS, and that the spinal canal size is not significantly associated with clinical symptoms among these patients.,12 Furthermore, previous studies have reported that the effects of the ESI are not associated with SS severity, based on spinal canal diameter assessment.,15Lumbar SS refers to the symptoms associated with the anatomical reduction of the lumbar spinal canal size. However, some individuals have a markedly narrowed canal without developing any symptoms, which raises the question of the role of central canal stenosis in symptom development. Moreover, the associations among dural sac stenosis and the numeric rating scale (NRS) pain scores or functional capacity  are not straightforward. The impact of the ESI on SS assessed using the novel criteria may be different from that assessed using conventional measures. In fact, some studies based on this new grading system have shown that the ESI may be an effective pain management tool in lumbar SS.,18 However, these studies assessed only the levels of pain associated with the degree of cauda equina separation rather than walking ability.Recent studies have proposed magnetic resonance imaging (MRI)-based assessment of the degree of cauda equina separation as an alternative method for disease severity measurement. As walking is critical to overall health, impaired walking ability may increase the risk of cardiovascular disease, thromboembolic stroke, diabetes mellitus, and cognitive disorders in older adults;–21 thus, restoring walking ability should be a treatment goal alongside pain management in patients with lumbar SS. In addition, adequate assessment of ambulation-related disability and levels of pain in patients who receive ESI is paramount to assessing treatment effectiveness. To the best of our knowledge, no previous study has investigated the effects of the ESI on pain scores and walking distance in patients stratified according to SS severity, assessed using the novel grading system. This study aimed to assess the impact of the ESI on pain scores and walking distance in patients with lumbar central stenosis, stratified according to the degree of cauda equina separation.Neurogenic claudication due to lumbar SS may impair walking ability in older adults.22.1This study involved a retrospective analysis of data from patients who received an ESI for lumbar SS at the pain management practice center of the Kangwon National University Hospital between July 2015 and November 2020. The study was approved by the institutional review board (No. KNUH-2020–12-016-002) and was conducted in accordance with the Declaration of Helsinki.This study included adults aged ≥50 years who received the ESI for management of lumbar spinal stenosis, experienced walking impairment due to lumbar SS, and had moderate or severe central canal stenosis in the lumbar spine MRI scan within 6 months before the ESI. The exclusion criteria were a presence of severe foraminal stenosis or herniated intervertebral disc with radiculopathy in the lumbar region; previous surgery to the lumbar spine or femur; administration of spinal corticosteroid injection within 6 months; or presence of any other disorders that could limit ambulation, including severe osteoarthritis of the hip or knee, severe cardio-vascular disease, chronic obstructive pulmonary disease, and neurologic deficits. Overall, 128 patients were included in this study and divided into moderate and severe SS groups after age-based (± 2 years) matching, including 64 patients per group. The following information was collected based on reviews of the participants’ medical records: medical history, pain scores, patient satisfaction scores, and intermittent claudication distance. The severity of the spinal central canal stenosis was assessed by a radiologist blinded to other study data, and classified as moderate and severe. The “moderate” stenosis category referred to the aggregation of some cauda equina, and “severe” stenosis referred to the absence of cauda equina separation, which created a bundle-like appearance , and limaprost.Lumbar SS was diagnosed based on medical history, including clinical symptoms, and physical, neurologic, and MRI examination findings. The SS diagnostic criteria were based on the North American Spine Society guidelines.nce Fig. .[16] MRI,23 A decrease in the NRS score of ≥2 points was considered indicative of a therapeutic effect. The patients’ walking capacity was expressed as a walking distance, ,25,26 which was measured as the maximum distance that a person could walk on a walking track at their own pace, without taking a break. Patients walked continuously until they were forced to stop or felt the need to stop due to the symptoms of SS. The NRS scores and walking distance were measured at baseline (before the ESI) and at 2 weeks after the ESI, to assess treatment effects. The degree of patient satisfaction was assessed using the Roland 5-point patient satisfaction scale  at 2 weeks after the ESI. Patients with Roland scale score of 0–2 points were considered “successful responders with improvement”.The patients’ pain levels were assessed using the NRS, with scores ranging from 0 (no pain) to 10 (worst pain) points.2.2 have suggested that a contrast agent may be distributed to more than one vertebral level, independent of the needle location, suggesting that an interlaminar ESI may be more beneficial than a transforaminal ESI in patients with central SS, as a higher volume of the injectate can be administered and distributed to a broader area with the former than with the latter method. Consequently, we used interlaminar ESI in our study, as did Sencan et al.. The ESI was performed as previously described. Briefly, all patients received lumbar ESI at the most stenotic level under fluoroscopic imaging, using the interlaminar method. The ESI included 8 mL lidocaine hydrochloride  and 5 mg dexamethasone, and was administered at the lumbar spine level. Two weeks thereafter, all patients returned to the clinic for treatment outcome assessments. No other interventions were offered to the study patients. However, the patients continued therapy with non-opioid analgesics and pursued normal activities, including work.In this study, we used an interlaminar ESI in patients with lumbar central stenosis. Weil et al. 2.3P-values of < 0.05 were considered statistically significant.Statistical analyses were performed using SPSS 25.0 . The data were presented as mean ± standard deviation or count (%). Among-group comparisons of demographic and clinical characteristics were performed using the Student t-test. Within-group comparisons of the parameters of interest at baseline and follow-up were performed using the paired t-test. The chi-square test was used to compare the differences in categorical variables among the groups. The normal distribution assumption of the data was verified with the Levene test. In all the comparisons, 3A total of 128 patients were included in this study and divided into moderate and severe SS groups, including 64 patients per group. The patients’ baseline characteristics are presented in Table P < 0.001, Table The proportion of patients with improvement in the degree of satisfaction was higher in the moderate group than in the severe group , respectively. In our study, the NRS pain scores decreased after the ESI; however, a decrease of the NRS score in the moderate and severe groups was 2.8 and 1.4 points, respectively (≥2 points considered indicative of a therapeutic effect). Moreover, the proportion of patients that experienced pain relief after the ESI was 64% and 31% in group with moderate and severe stenosis, respectively. The higher proportion of patients that experienced pain relief after the ESI in the present than in the previous study by Do et al. might have been due to the higher initial pain score among the patients in this study; the corresponding baseline NRS scores were 7.1 and 4.6 points, respectively. The patients in our study might have been more satisfied with the effects of the ESI due to higher baseline pain levels. Furthermore, in the study by Do et al., the reduction in pain scores was more pronounced in the patients with moderate SS than in those with severe SS; this finding was consistent with that of our study. Moreover, the group with severe SS in our study showed poorer outcomes than that with moderate SS. This finding may be accounted for by the SS classification criteria used, which consider the extent of nerve compression in symptomatic patients. Meanwhile, in a study by Park et al., the ESI provided effective pain relief in lumbar SS; however, the grade of lumbar SS appeared unrelated to the degree of pain relief obtained with the ESI. This discrepancy in findings might have been due to the small number of patients with severe SS who were included in the study by Park et al. (n = 6).Few studies have assessed the severity of lumbar central stenosis based on the degree of cauda equina separation.,5,26 Recently, Sencan et al. have reported that walking distance increases in patients with lumbar central stenosis following the administration of an interlaminar ESI. Our findings were consistent with those of this study, which might have been due to the decrease in peri-neural inflammation, edema, and pain levels. The present study is first to investigate whether SS severity graded according to the degree of cauda equina separation affects walking ability after the ESI in patients with lumbar central stenosis. In the present study, walking distance increased in the moderate group after the ESI; however, it remained unchanged in the severe group. This finding suggests an association between walking ability following the ESI and the grading of SS severity. The lack of change in this parameter in the severe group suggests that severe SS may be an advanced disease; this observation is further supported by the shorter walking distance observed in this group than that observed in the moderate group.Walking difficulty is a characteristic of lumbar SS in patients with neurogenic claudication, where improved walking ability is the primary treatment goal. However, treatments to improve walking capacity remain controversial.,25 In this study, the corresponding value was 48%. The relatively low proportion of patients showing improvement in this study may be due to a higher proportion (50%) of patients with severe stenosis in this than in the previous studies. The proportion of patients with improvement in the moderate and severe groups was 64% and 31%, respectively, with the lowest number of patients reporting improvement in the severe group. Based on these findings, pain management physicians should inform patients with severe SS that the effectiveness of an ESI in their condition may be unsatisfactory.In previous studies, the proportion of patients with lumbar SS reporting improvements after the ESI was in the range of 52–77%.,7,10,11 However, clinical trial and systematic review findings suggest that the ESI may help relieve pain and improve functional outcomes in patients with lumbar SS.–9 Previous studies have reported an NRS score decrease of 3.1–6 points within 6 weeks to 3 months after an interlaminar ESI in patients with lumbar central stenosis.–8 In this study, 2 weeks after the interlaminar ESI, the NRS pain scores decreased by 2.1 points. The reason for this relatively small reduction in pain scores might have been associated with the differences in the medications used , and in the patients’ demographic characteristics. Moreover, the patients had similar pain scores at baseline, independent of their SS severity; these patients presented at a pain clinic for pain management rather than for other types of intervention, which may account for these similarities.The impact of the ESI on lumbar SS remains controversial.,15,18 Third, the outcomes considered in this study, such as NRS pain scores and walking distance, were subjective. However, in this study, we focused on improving symptoms  in patients with lumbar spinal central stenosis. Prospective randomized controlled trials are required to investigate the effect of the ESI in patients with lumbar foraminal stenosis.This study has some limitations. First, this was a single-center observational study. However, to reduce selection bias, we used restrictive eligibility criteria and included patients who were similar in age, lifestyle, and baseline pain scores. Second, this study assessed short-term outcomes. Previous studies have suggested that the effects of an ESI are short-lived and may disappear within 3 weeks to 6 months after the injection.5In conclusion, lumbar interlaminar ESI may reduce pain scores and increase walking distance in patients with moderate lumbar spinal central canal stenosis. In the present study, patients with moderate SS presented with outcomes that were better than those of patients with severe stenosis.This study has received no specific funding. We would like to thank Editage (www.editage.co.kr) for English language editing.Conceptualization: Byeongmun Hwang, Minsoo Kim.Data curation: Minsoo Kim, Soyeon Cho.Formal analysis: Hee-Jeong Son, Jin Huh, Seong-Sik Kang.Investigation: Daehun Goh, Soyeon Cho, Yeonji Noh.Supervision: Byeongmun Hwang.Writing – original draft: Byeongmun Hwang.Writing – review & editing: Byeongmun Hwang.


Pulsed radiofrequency, short bursts of radiofrequency energy, has been used by pain practitioners as a non- or minimally neurodestructive technique, an alternative to radiofrequency heat lesions. The clinical advantages and mechanisms of this treatment remain unclear. To review the current clinical implication of the pulsed radiofrequency technique for male patients with chronic scrotal pain. We systematically searched the English literature available at the EMBASE, MEDLINE/PubMed, Google Scholar, and Cochrane Library from inception to 22 November 2022. Only reports on a pulsed radiofrequency application on male patients with chronic scrotal pain were included. The final analysis yielded six reports on the clinical use of pulsed radiofrequency applications in male patients with chronic scrotal pain: six full publications, three case reports, one case series, one prospective uncontrolled pilot study, and one prospective randomized, controlled clinical trial. The accumulation of these data shows that using pulsed radiofrequency generates an increasing interest in pain physicians, radiologists, and urologists for managing chronic scrotal pain. No side effects related to the pulsed radiofrequency technique were reported to date. Further research on the clinical and biological effects is justified. Large sample sizes and randomized clinical trials are warranted. Worldwide, chronic pain is one of the major public health problems and is one of the leading causes of years lived with disability (YLDs) . Chronic scrotal pain (CSP) “Chronic orchialgia” is defined as intermittent or constant, unilateral, or bilateral pain, localized to the scrotal structures, three months or longer in duration that significantly interferes with the daily activities of the patient and prompts him to seek medical attention .CSP is frustrating for both the physician and the patient. Managing patients with chronic pain is difficult, frustrating, and time-consuming for the urologist and the patient. It is the cause of about 2.5% to 5% of all urology consultations and currently affects about 100,000 men in the United States each year .Chronic orchialgia may include infection, tumor, inguinal hernia, hydrocele, spermatocele, varicocele, referred pain, trauma, and previous operations . Nearly 25% of patients with chronic orchialgia have no apparent cause for the pain .This condition has been referred to by many names, including chronic orchialgia, testicular pain syndrome, testalgia, chronic scrotal content pain, post-vasectomy orchialgia, post-vasectomy pain syndrome (PVPS), congestive epididymitis, and chronic testicular pain . Chronic orchialgia is used frequently to describe what is better described as chronic scrotal content pain (CSCP), as the pain may involve the testicle only and/or the epididymis, para-testicular structures, and the spermatic cord . For simThe ilioinguinal nerve and the genital branch of the genitofemoral nerve innervate the testis’s major somatic sensory innervation. Genital pain, on the other hand, can be felt in any organ or tissue that shares the same L1–L2 or S2–S4 neural pathways as the scrotum or testicles. Orchialgia can be caused by any inflammatory, traumatizing, or infectious stimulus to the scrotal nerves. Testicular pain could be caused by low back pain or radiculitis, which affects the nerve roots from T10 to L1.Ureteral stones can produce testicular pain because the testis and the upper ureter have sensory fibers that use spinal cord segments T11 and T12.Dysfunction or spasms of the pelvic floor muscles can be linked to CPPS, although they can also occur in some chronic orchialgia patients.Multiple algorithms for diagnosing and treating CSP have been proposed, but none have been validated . It is aThere are many different modalities for CSP management ranging from conservative management as the first-line treatment in most cases, including heat or ice compression, scrotal elevation, antibiotics, analgesics, local and regional nerve blocks, pelvic floor physiotherapy, biofeedback, acupuncture, and psychotherapy for at least three months. Some cases may indicate surgical intervention when failed conservative management occurs; if the spermatic cord block is only 50% effective in reducing orchialgia, surgical intervention is indicated, including varicoceles or epididymectomy or microsurgical denervation of the spermatic cord (MDSC). Pulsed radiofrequency (PRF) therapy to denervate the spermatic cord has been tried with encouraging early results, although its final efficacy and duration are still uncertain .Based on the best practice report on chronic scrotal pain from Canadian Urological Association, PRF denervation remains  .The biological effects of the radiofrequency (RF) field have been investigated ,7,8. TheSearch strategy and information source: We searched seven databases via EMBASE, MEDLINE/PubMed, Google Scholar, and Cochrane Library. The included databases were searched from inception until 22 November 2022, including only English literature using search terms: pulsed radiofrequency AND chronic scrotal pain AND chronic testicular pain AND orchialgia.Study selection and data extraction: Conducted in a standardized excel sheet that included the IDs, authors, URL, DOI, journal and database name, and abstracts to facilitate the screening process and hasten our study efficiently. Two reviewers independently screened each title/abstract of retrieved records and full texts of retrieved studies for possible inclusion discrepancies, which were resolved by senior authors who were consulted whenever needed. We extracted the following data: the surname of the first author, year and country of publication, study design, details about intervention (treatment protocol and device used), number of participants, baseline characteristics of participants, pain level pre- and post-PRF treatment, follow-up period and outcomes about efficacy and safety.Eligibility criteria: The study inclusion and exclusion criteria for reviewed articles are summarized in . We inclhttps://jbi.global/critical-appraisal-tools, accessed on 15 October 2022). Two reviewers extracted data independently using a pre-designed table to summarize study results, which included author, year, study design, and outcome measure information.We included studies where PRF treatment was directed to the dorsal root ganglion (DRG) or peripheral nerves. If the study only reported results about efficacy and safety was not reported, we still included such a study to achieve a comprehensive evidence synthesis regarding efficacy. Each study was evaluated using the Joanna Briggs Institute Quality Assessment Tool (Outcome measures: Primary outcomes were pain intensity and serious adverse events (SAEs). Secondary outcomes for efficacy were any other pain-related outcomes and safety data, including non-serious adverse events and other complications regarding intervention.Synthesis of results: We conducted a narrative and tabular synthesis of the results. We also analyzed the conclusiveness of efficacy and safety of the treatment in the abstracts of the included studies. For this reason, due to the heterogeneity of included studies, it was not possible to conduct a systematic analysis, even though we had planned to do it in our study protocol.We screened manuscripts in the full text, including six studies in this literature review. The total number of participants in these manuscripts was 55 patients, one prospective randomized double-blinded controlled trial including 30 patients, one prospective uncontrolled pilot study including nine patients, one case series of five patients, and three different case reports of three patients. Eight patients have been excluded, four were lost to follow-up, and four did not match the inclusion criteria. In these studies, a total of 47 patients were subjected to RFA for the treatment of CSP. Detailed information about inclusion and exclusion criteria and baseline characteristics of included participants are listed in . StudiesOnly five patients had no treatment before RPF, 42 patients underwent conservative management, including antibiotics, analgesics, anti-inflammatory agents, or antidepressant drugs, and five patients had transcutaneous electrical nerve stimulation (TENS). Moreover, all the patients underwent diagnostic cord blockage before RPF. Forty-six patients had PRF at the spermatic cord in the setting of 2-Hz frequency, 20-ms pulses in one cycle, 120-s duration, and 42 °C temperature, except one patient who had a duration of RPF for 180 s. However, one patient received PRF at the dorsal root ganglia in the setting of 2 Hz, 8 ms pulse duration, max 45 V, and max 42 °C for 8 min . The durp = 0.001). Prospective studies: We found one prospective randomized, double-blind, controlled clinical trial including 60 patients with three months follow-ups. The percentage of patients that showed >50% reduction of their visual analog scale (VAS) pain score and the percentage of patients that did not require additional analgesic drugs were assessed. In 50% of patients that did not require analgesic drugs, the mean post-procedural VAS pain reduction was significant . Both studies showed that no side effects were reported during the treatment and follow-up periods. p < 0.05). The mean follow-up period was 20 (±) 2.5 weeks. None of the patients needed any analgesics after the procedure or during the follow-up. However, Scrotal Doppler ultrasonography was performed to evaluate the volume changes of the testis in the 12th week, and no complications were reported, and no recurrence was noted.Case Series and Reports: In one case series including five patients, the median VASs before intervention was 9, and the mean VAS, 3 weeks after the procedure was 1 showing a significant reduction of VAS scores  pain score.It is important to determine whether the pain is referred to or originated from the testes to treat chronic orchialgia. For differential diagnosis, diagnostic cord blockade must be performed. If the pain relief occurs several hours after the diagnostic cord blockade in a patient with chronic orchialgia, the pain originates from the testes ,18,19,20Cohen and Foster studied all nerve blocks performed at the first visit according to standard practice and procedures ,22. FurtAll reviewed studies used the visual analog scale (VAS), a 10-point (0 = no pain to 10 = worst pain)  to evaluOne study used the short-form McGill Pain Questionnaire (SF-MPQ) , which iSluijter used this machine in early 1996 to conduct preliminary clinical trials and wrote the first report on the clinical effects of PRF on the dorsal root ganglia in 1998 .PRF uses radiofrequency current in short (20 ms), high-voltage bursts; the “silent” phase (480 ms) of PRF allows time for heat elimination, generally keeping the target tissue below 42 °C within the range requisite for tissue destruction, as demonstrated by Cosman and Cosman . It doesPRF ablation allows heat dissipation and is usually applied up to 40–42 °C by applying “pulses” of radiofrequency energy with intervening pauses ,29. PossPRF has successfully treated painful metastatic tumors involving the brachial plexus and spinal facet pain, trigeminal neuralgia, chronic shoulder pain, cervical radicular pain , and refThe first series of applied PRF has been published on the subject involving four patients with sciatica or post-thoracotomy pain, which purportedly works through the induction of an electromagnetic field . It is cThe total number of participants was 47 patients. Age , pain duration, and follow-up were also summarized in . One stuTreatment options for chronic orchialgia include nonsurgical , and pulsed radiofrequency) and surgical  guidance, laparoscopic denervation of the spermatic cord, microsurgical denervation of the spermatic cord, microsurgical testicular denervation, epididymectomy, and orchiectomy) procedures ,33,34. MThe perspective on treating chronic orchialgia clearly shows that the main advantage of PRF from surgical denervation procedures is that this is a minimally invasive technique with no adverse effects. PRF does not damage the nerve. The absence of neuroma formation may explain its increased success rate . Cohen aThe procedure duration mainly ranged from 2–3 min without any medication or analgesic needed post the procedure. Moreover, in Misra et al.’s paper PRF was used  with the following settings: 2-Hz frequency, 20-ms pulse, and 120-s cycles for a total of 8 min; the output voltage was adjusted for the temperature not to exceed 42 °C . Interestingly, all the patients reported an excellent outcome with the variation of the analgesia type and doses, technique, and procedure duration of RPF considering patients’ demographic factors, i.e., BMI and subjective pain before and after the procedure. However, conducting randomized placebo-controlled trials in interventional pain management has methodological and ethical limitations . TherefoA review of prospective longitudinal studies concludes that PRF exhibits a high safety margin in various conditions, including discogenic pain, chronic inguinal herniorrhaphy pain, and chronic testicular pain. They demonstrate the use of PRF in various indications and, in some instances, showed positive results where conventional treatments, on average, failed. However, these studies are subjected to a great degree of publication bias. Its efficacy, however, needs to be verified against identical control subjects. There also exist unanswered questions regarding the effective “PRF dose” based on voltage settings and duration of PRF treatment which require further clinical studies to substantiate . p < 0.05) [p < 0.01). Moreover, there was a significant reduction in the mean VAS score (between groups) at all of the measured time points  (p = 0.001) in the PRF group [Mean VASs before and three weeks after the procedure were 9 and 1, respectively. The differences between pre–PRF procedure and post–PRF procedure VAS scores were statistically significant ( < 0.05) . Hetta eRF group .This study is not without limitations. The number of patients in this review is insufficient to draw firm conclusions, but the results are encouraging. The majority of reported studies’ follow-up was relatively short, which may affect the review’s depth and rigor. The strength of this review is that it is considered to provide the first insight in the English literature on available information and outcomes regarding the effect of RFA on chronic orchialgia. Pulsed radiofrequency (PRF) is promising and encourages a minimally invasive treatment for chronic scrotal pain with a high safety and tolerability profile. However, more extensive studies are needed with extended follow-up before any evidence-based recommendations can be made.


Studies on MRI findings among patients with LBP have been conducted; especially among adolescents and young adult population in developed countries. However, MRI lumbar spine evaluation findings in young adult patients with low back pain in Uganda is not known. The purpose of this study was to determine the MRI findings and their correlation to clinical features in young adult patients with low back pain in Nsambya hospital.p values reported at 0.05 level of significance.This was a descriptive cross sectional study. One hundred and fifty-seven patients with low back pain in the 18–39 year age group underwent MRI lumbar spine evaluation. The MRI changes in the lumbar spine and correlation to clinical features were determined. Correlation was assessed by Pearson chi square tests (Fisher’s exact test) and Of the 157 patients 129 (82.2%) had severe pain, whereas ninety (57.3%) had pain that had lasted more than 10 weeks. Sixty-five (41.4%) patients were found to have MRI evidence of disc desiccation, majority (61%) of whom had multiple level disease, mostly involving the lowest 2 disc levels. Facet joint arthropathy (47.8%), marginal osteophyte (31.8%) and disc contour irregularity [disc bulge] (31.2%) were other common MRI features seen. There was an association between duration of pain and limb weakness, and development of marginal osteophytes. There was also association between clinical presentation and disc bulge.The MRI finding of disc degeneration among young adult patients with LBP is higher than reported. Age and pain distribution are predictors of developing disc desiccation. Low back pain (LBP) is a common health problem with a global prevalence of 20% . The annMagnetic resonance imaging (MRI) has played a significant role in evaluating lumbar-sacral spine as it is able to show clearly any anomaly of the vertebrae, intervertebral disks, spinal cord, the neuroforamina, ligamentum flavum, facet joints and the longitudinal ligaments. The clinicians and most patients now prefer MRI to radiographic evaluations because of its high spatial resolution ability providing images that will offer diagnosis of a disease, monitoring treatment response and follow up of patients since it provides conclusive results. It is also used to determine extent of a disease and in follow up of patients. MRI is indicated in most conditions such as severe progressive neurologic deficit, persistent low back pain with features of radiculopathy, spinal stenosis, or when a patient is to undergo surgery where plain x-ray would provide inconclusive results .Certain lifetime occupation and activities have influenced the development of lumbar spine degeneration diseases , such acThe Modic changes had no gender difference with Modic type 1 being more common than type 2 and were located adjacent to a disc degeneration . Other sThe purpose of this study was to determine the MRI findings and their correlation to clinical features in young adult patients with low back pain in Nsambya hospital.This was a cross-sectional descriptive study in which images of young adults with LBP were reviewed.The study was conducted in the department of radiology of Nsambya Hospital. The hospital offers both outpatient and in-patient services. It is a 361-bed capacity private-not-for-profit hospital located in the southern part of Kampala city approximately 3 km from the city center. It has a radiology department equipped with 1.5Tesla Siemens MRI, 128 slides computed tomography (CT) machine, 04 ultrasound machines, conventional x-ray machine and mammography machine. The department on average receives 86 patients with low back pain for MRI evaluation every month and between 15 and 17 will be young adult patients. However, this number increases during national inter school’s/Universities sports seasons.Consecutive sampling of young adults aged between 18 to 39-years old who are to undergo MRI lumbosacral spine evaluation after referral to the department.Participants were recruited at the MRI room reception station and written informed consent were obtained. Bio-data, Clinical detail and level of physical activity were obtained and recorded.The MRI scan of the lumbar spine was performed with a 1.5 Tesla MRI machine  using a dedicated receive—only spine coil, and a standard protocol specification for young adult in sagittal T1W, T2W, T2W STIR, T2W myelo, sequences. Coronal/axial reformats at levels T12-S1 were obtained. In suspected neoplastic and inflammatory processes the images were acquired in T1WI with Contrast, and gradient echo (GRE) sequences.The MRI images were viewed at the picture archiving and communication system (PACS) GE  workstations. The corresponding radiological reports were made by the principal investigator and supervised by two consultant radiologists with substantial experience in neuroradiology imaging. Any difference in opinion was settled by consensus.Data was captured for every image using a data collection form that was de-identified to exclude any unique identifier that would reveal the identity of the image. All study data forms were checked for accuracy, completeness and consistency regularly and any identified errors was corrected on the spot. All forms with completed data were sorted, and coded with unique study identifiers.Frequency and proportions of variable were determined using descriptive statistics. Continuous variables were summarized in median and inter quartile range. Median and interquartile ranges were used because the data were not normally distributed.p values less than 0.2 at 95% confidence intervals were considered for multivariate analysis. Interaction and confounding were assessed in the regression model to determine the factors that are associated with low back pain. Variables with p < 0.05 was considered statistically significant.Multiple logistic regression analysis was done using Stata 13.0 to find clinical and MR factors associated with spine image characteristics. Odds ratios (ORs)) were calculated to measure the effect of an independent variable on the outcome variable. Bivariate analysis, for independent variables was used and those which have Permission to conduct the study was sought from, and granted by the Department of Radiology. Institutional approval for the study was sought from, and granted by the Makerere University School of Medicine Research and Ethics Committee on June 24th, 2019 (REC REF 2019-096). All study activities and procedures were conducted per Good Clinical and Laboratory Practice starting June 27th, 2019 and ended on June 26th, 2020. All patients were briefed about the study; background, aim, risks, benefits and expectations for participation before being consented to participate. Written informed consent  were sought from each of the prospective participants in the study prior to enrolment and data collection. All data and results generated from this study were kept confidential and were only accessed by a few authorized personnel. Preliminary examination of patients to assess whether or not they had red flags, other diseases for which they could not undergo MRI or be part of the study was conducted at the hospital’s orthopedic department. Illegible participants were advised on the next step according to the routine standard practice at the department.Of the 157 patients  who Eighty-seven (55.4%) patients had gradual onset of pain whereas 70 (44.6%) had sudden onset; 129 (82.2%) patients had severe pain and most of which were burning in nature . Majority of the patients had radiating pains  that was frequently aggravated by bending down  and alleviated by lying down .The median duration of pain was 4 weeks, with a minimum duration of 1 week and maximum of 14 weeks. Sixty-seven 42.7%) had acute pain whereas ninety (57.3%) patients had chronic pain. Six (3.8%) patients had lower limb weakness; 4 (66.7%) had weakness of both lower limbs as shown by Table .7% had aIntervertebral disc (IVD) protrusion was observed in 48 1.9%) patients at levels L3/L4, L4/L5 and L5/S1 [as shown by Fig. % patientSeventy-five (56.3%) patients had multiple level disease, commonly involving L4/5 and L5/S1 levels [as shown by Figs. The most common MRI feature observed was reduced disc signal intensity [as shown by Figs. Under bivariate analysis, patients’ age and pain distribution were associated with disc desiccation.p = 0.002). Those in the age group of 35–40 years were 2.22 times more likely to develop disc desiccation when compared to other age groups and the difference was statistically significant (p = 0.022).The age group of 23–35 years was associated with presence of disc desiccation. The risk of patients developing disc desiccation was found to increase with age. Patients in the age group of 23–35 years were 1.81 times more likely to develop disc desiccation than those in age group of 18–22 years and the difference between the two age groups was statistically significantly (p = 0.006) as shown in Table Distribution of pain also predicted the occurrence of disc desiccation under bivariate analysis in this study. Those who were presenting with radiating pain were 2.58 times more likely to have disc desiccation than those with localized low back pain (49 cases versus 17 cases) and the difference was statistically significant (p = 0.004). Likewise, the odds of the patients in the age group of 35–40 years to develop disc desiccation was 2.42 more than those in the age group of 18–24 years and the difference was statistically significant (p = 0.029). Distribution of pain among the patients continued to be associated with disc desiccation in the study. The risk of patients with radiating low back pain was 1.23 times more than those with localized low back pain with statistical significance difference (p = 0.024) as shown in Table When the two independent factors (age and distribution of pain) were subjected to multivariate analysis and after controlling for all other independent factors, it was found that, both factors remained predictors of the outcome (disc desiccation). The risk of the patients with age group 25–34 years was 11.42 times more than those in the age group of 18–24 years and the difference was statistically significant . Occupational and limb weakness both showed marginal association with marginal osteophytes (p = 0.06). There were more patients with informal occupation (37 patients) who had marginal osteophytes compare to 35 patients with formal occupation who had marginal osteophytes, however, the difference was not statistically significant (p = 0.06) and they were 20% more likely to have marginal osteophytes as shown in Table Marginal osteophytes were the other MRI findings examined in this study and their presence were associated with the different independent factors included in this study. Only duration of LBP was the predictor of marginal osteophytes under bivariate analysis. Patients who had low back pain for the duration more than 10 weeks were 99.93% more likely to be diagnosed with marginal osteophytes than those who had low back pain for ≤ 10 weeks and the difference was statistically significant (p = 0.96) although there were more patients with marginal osteophytes (61 cases) among those who had low back pain ≤ 10 weeks compared to the ones who had low back pain for the duration of > 10 weeks as shown below in Table After adjusting for other covariates in multivariate analysis, duration of pain became not predictive of marginal osteophytes p = 0.6 althougWe have reported on young adult patients with LBP in Nsambya hospital. The present study described the MRI findings in the lumbar spine which included decreased signal intensity, changes in disc contour  marginal osteophytosis and facet joint osteoarthritis.Disc desiccation was the most common disc finding in our study, and increased infrequency with age , 8 whichIn a study from Finland on a group aged 20–22 years, Takatalo et al.  found a In the current study, the frequency of MRI lumbar spine disc changes appears to be higher (47.7%) when compared to other reports in literature , 25, 26 The non-disc changes of degeneration that was observed comprised marginal osteophytes, foraminal stenosis with nerve root compression, end plate irregularities, spinal canal stenosis and facet joints arthropathy. Facet joint effusion (48%) and osteophytes (32%) were the most common. Our observation is consistent with observations from other studies . LiteratStatistical analysis confirms that age, pain distribution and duration of pain as the independent factors which associated with abnormal MRI findings in our study. This is supported by a large population based study from Norway , Middle The sample size was small to give a general picture of Uganda’s population.Several images with MR findings that would aid in the understanding of the findings were absent.Pain lasting more than 10 weeks is the most common clinical presentation among patients with LBP.Disc contour irregularity, disc desiccation and loss of disc height are the most common findings in patients who present with severe LBP of acute onset in this study.Disc bulge is the most common MRI finding in patients with LBP.Disc desiccation is common among patients above 24 years of age who present with LBP. However, there is no association between sex, occupation and activity levels with disc desiccation.Disc bulge and marginal osteophytes show no association with age, occupation and activity levels.LBP which is radiating in nature is the most common finding in patients with disc protrusion in this study.Severe burning pain of gradual onset is common among patients with severe disc bulge and osteophytes.


The only significant factor associated with increased odds for severe pain was the standard of care compared to NOL treatment . The use of a machine learning-based technology to guide opioid dosing during major abdominal surgery resulted in reduced PACU pain scores with less patients in severe pain.In this pooled analysis of two randomized clinical trials, intraoperative opioid dosing based on the nociception level-index produced less pain compared to standard care with a difference in pain scores in the post-anesthesia care unit of 1.5 (95% CI 0.8–2.2) points on an 11-point scale. The proportion of patients with severe pain was lower by 70%. Severe postoperative pain remains a significant problem and associates with several adverse outcomes. Here, we determined whether the application of a monitor that detects intraoperative nociceptive events, based on machine learning technology, and treatment of such events reduces pain scores in the post-anesthesia care unit (PACU). To that end, we performed a pooled analysis of two trials in adult patients, undergoing elective major abdominal surgery, on the effect of intraoperative nociception level monitor (NOL)-guided fentanyl dosing on PACU pain was performed. Patients received NOL-guided fentanyl dosing or standard care (fentanyl dosing based on hemodynamic parameters). Goal of the intervention was to keep NOL at values that indicated absence of nociception. The primary endpoint of the study was the median pain score obtained in the first 90 min in the PACU. Pain scores were collected at 15 min intervals on an 11-point Likert scale. Data from 125 patients  were analyzed. Sixty-one patients received NOL-guided fentanyl dosing and 64 standard care. Median PACU pain score was 1.5 points (0.8–2.2) lower in the NOL group compared to the standard care; the proportion of patients with severe pain was 70% lower in the NOL group ( To this end, a novel monitor, the Nociception level (NOL), was developed with machine learning technology, that reliably tracks the patient nociceptive state and prompts analgesic dosing when the objective measure of nociception is high  is not detected during general anesthesia, particularly not when muscle relaxants are administered. Hormonal responses  –3. In adraction) –7. One a is high –12. We d is high . Note thi.e., from no nociception to extreme nociception. Validation studies showed with confidence that a NOL value of 25 distinguishes between non-nociceptive (NOL < 25) and nociceptive events (NOL > 25)  –11. TherTo strengthen our knowledge on the relationship between NOL-guided analgesic dosing during surgery and postoperative pain scores, we conducted a pooled analysis of two independent, randomized, controlled trials that compared the influence of intraoperative NOL-guided fentanyl to standard of care (SOC) on postoperative pain , 13. TheThis is pooled analysis of two earlier conducted and published trials with a similar protocol, the SOLAR trial and the Abdomi-Nol trial , 13. BotBoth studies utilized the PMD-200 nociception monitor, manufactured by Medasense Biometrics Ltd. . The device integrates several physiological variables that are known indicators of sympathetic activity to provide a single index of nociception, the NOL index. The PMD-200 sensing unit consists of a finger probe with four distinct sensors: photoplethysmogram, galvanic skin response, accelerometer, and a thermistor. The information from the accelerometer and the thermistor are used as a guardrail to ensure the algorithm performance but is not directly incorporated into the NOL calculation. Thousands of samples of these physiological variables  and their derivatives were recorded during major surgery of adult anesthetized patients and were annotated by expert clinicians for stimuli intensity and level of analgesia. These data were then used to train a random forest machine learning model, which is at the heart of the NOL algorithm. Although the model is locked, the algorithm “personalizes” its nociception index to the individual patient by implementing an adaptive weighting mechanism between the static model and the patient's unique physiologic responses during the surgical procedure. As the case progresses, the weighting of the patient's unique physiological response increases and the NOL output is adjusted accordingly. Separate datasets were used by the manufacturer to train, test and validate the NOL index .i.e., NRS < 4. In both studies SOC was identical and was performed according to widespread clinical practice. In brief, but see for details below, fentanyl was given preemptively, prior to induction, followed by dosing base don the patient's condition and course of surgery, preferably isn such a way that hypertension and tachycardia were prevented. Still, in case of such hemodynamic instabilities further fentanyl was administered.In both studies, the NOL monitor finger clip was connected to the patient on the left or right middle finger before induction. In case of NOL-guided fentanyl dosing, the monitor screen was visible to the anesthesia providers. In case of SOC, the screen of the monitor was concealed. Pain scores in the PACU were obtained at 15 min intervals and intravenous doses of opioids were given according to local protocol until pain scores were considered acceptable , SOLAR study . This was left to the discretion of anesthesia care giver and based on local protocol.As stated above, in both groups preemptive fentanyl was given prior to intubation followed by dosing to preemptively prevent hemodynamic instabilities. The only difference between the NOL-guided and SOC groups was the trigger to administer additional fentanyl. In the test group, fentanyl dosing was dependent on the NOL-index, but blood pressure and heart rate were considered as well. In case the NOL index >25 for at least 60 s, 50–100 Abdomi-Nol study .The primary endpoint of both studies was the NRS for pain obtained by the PACU nursing staff in the first 90 min in the PACU. NRS < 4 was considered mild and acceptable, NRS from 4 to <7 moderate pain and 7 or higher severe pain. Pain scores of 4 or greater were treated in the PACU using a multimodal approach consisting of acetaminophen and/or an opioid. In the analyses, we highlight severe pain and maximal pain scores, as we consider these most agonizing and harmful to the patient.U tests: p > 0.05 at all times points). The distribution of continuous variables was assessed using Shapiro & Wilk test. Continuous variables with non-normal distributions were expressed as median and interquartile range. Categorical variables were expressed as number and percentage. Comparisons of continuous variables between groups were performed with the Mann-Whitney U test for nonparametric variables, and the Fisher's exact-test or χ2-test for categorical variables. A logistic regression model was used to identify factors related to severe pain. Generalized linear models with the cluster bootstrap were applied to evaluate the difference in NRS accounting for the repeated measurement for each subject during the 90 min in PACU. This model was also used to evaluate the differences in specific subgroups. Pearson correlation coefficient were calculated for opioid dose during surgery vs. NRS in the PACU. P-values <0.05 were considered significant. Data were analyzed in R-4.0.3 , SPSS Statistics . The raw data included in the study are available from the authors after agreement on purpose and protocol.Prior to data pooling a comparison of general patient's characteristics between the 2 studies was conducted and there were no significant differences between the studies, except for surgery type distribution . AdditioThe study protocols , enrollep = 0.002).The primary endpoint, postoperative pain during the first 90 min in the PACU, is presented in 2  or body mass index > 30 kg/m2 , patients undergoing urological surgery  and patients undergoing abdominal surgery .To identify specific patient populations that benefit from NOL-guided analgesia, generalized linear models with the cluster bootstrap were applied for each subgroup. Subgroups with the lower limit of the 95% confidence interval > 0 were: females , patients ≤ 65 years , ASA 1 patients , patients with a body mass index < 25 kg/mp = 0.001) with 66% of patients in the NOL-guided group that had pains scores < 4 throughout their stay in the PACU vs. 10% in the SOC group. The number of patients with severe pain (NRS ≥ 7) was 11 in the SOC group and 3 in the NOL-guided group, p = 0.045 (p = 0.017). None of the other factors reached the level of significance.The highest pain scores observed at any time throughout the 90 min stay in the PACU were 4.6 (NOL-guided group) and 6.2 , we observed that intraoperative NOL-guided analgesia reduced the proportion of patients with pain scores ≥ 4 (at any time in the PACU) from 90% in SOC patients to 66% following NOL-guided analgesia. This means that while 90% of SOC patients required a treatment for their pain postoperatively, this was true for just two-thirds of the NOL-guided patients; in other words, one-third of the NOL-guided patients did not require any opioid or any other pain medication in the PACU. Logistic regression analysis  improved PACU pain scores, (2) fewer patients with severe pain, (3) a greater proportion of patients who did not require any opioid treatment in the PACU compared to standard care; lastly, (4) our analysis showed that the predictor of less severe pain in the PACU was NOL-guided fentanyl dosing. These finding are pertinent and may aid in minimizing the prevalence of severe pain after surgery and all of its negative repercussions.Relating to this last remark, it is important to reflect on the consequences of less PACU pain and a reduced number of patients that required opioid treatment in the PACU in light of the current opioid crisis. One of the causes of the opioid crisis, at least in the Netherlands, is the fact that hospital stay is currently relatively short and many patients are discharged from the hospital, while still in pain, with an opioid prescription . Althoug


Chronic low back pain (CLBP) due to osteoarthritis represents a therapeutic challenge worldwide. Opioids are extensively used to treat such pain, but the development of tolerance, i.e., less susceptibility to the effects of the opioid, which can result in a need for higher doses to achieve the same analgesic effect, may limit their use. Animal models suggest that ultra-low doses of opioid antagonists combined with opioid agonists can decrease or block the development of opioid tolerance. In this retrospective study, we tested this hypothesis in humans. In 2019, 53 patients suffering from CLBP were treated with either Oxycodone and Naloxone Prolonged Release  or Oxycodone Controlled Release . The follow-up period lasted 2 years, during which 10 patients discontinued the treatment, 5 out of each group. The remaining 43 patients reached and maintained the targeted pain relief, but at 18 and 24 months, the OXY patients showed a significantly higher oxycodone consumption than OXN patients to reach the same level of pain relief. No cases of respiratory depression or opioid abuse were reported. There were no significant differences in the incidence of adverse effects between the two treatments, except for constipation, more common in OXY patients. From our results, we can affirm that a long-term opioid treatment with oxycodone-naloxone combination, when compared with oxycodone only, may significantly hinder the development of opioid tolerance. We were also able to confirm, in our cohort, the well known positive effect of naloxone in terms of opioid-induced bowel dysfunction incidence reduction. Chronic pain is “a pain which persists past the normal time of healing ” and is Although most opioid side effects subside with chronic use, OIBD mostly persists , and it The most common symptom of OIBD is constipation, which occurs in approximately 40% of patients and can negatively affect patients’ quality of life ,15,16. TAnother limit of long-term therapy with opioids is the development of tolerance to their analgesic effect. Opioid tolerance is characterized by a reduced susceptibility to the effects of the opioid, which can result in a need for higher and more frequent doses to achieve the same analgesic effect, possibly further limiting the clinical utility of these drugs ,24. Alth®, Mundipharma, Cambridge, UK) or oxycodone alone , from January to December 2019. A rigorous outpatient follow-up appointment schedule was applied, with checkpoints at 0, 1, 3, 6, 12, 18, 24 months from baseline visits. At our pain center, opioid treatment for chronic non-oncological pain is routinely prescribed after compiling the Opioid Risk Tool (ORT), a validated screening instrument commonly and widely used in clinical practice to exclude patients with high or moderate opioid addiction risk [In this retrospective study, we collected data from all CLBP patients with a score > 60 according to the Visual Analogue Scale  who visited our pain treatment center at the Borgo Roma Hospital in Verona and started a treatment with orally administered oxycodone-naloxone combination  guidelines.We performed a retrospective analysis of data collected from January 2019 to December 2021 and referring to the whole year of 2019. All clinical data were assessed at our department by the physicians during the institutional scheduled medical examination for CLBP patients . The collected clinical data inquired about the VAS score changes from baseline to the standardized subsequent checkpoints, as routinely done in our center. We further analyzed the total daily consumption of opioids and the bowel function using the Bowel Function Index (BFI) to assess opioid-induced constipation . FrequenThe statistical analysis was performed comparing data of patients treated with oxycodone only versus those treated with oxycodone and naloxone using non-parametric tests, more robust than parametric. Descriptive statistics were reported in terms of medians and interquartile range for quantitative variables and in terms of absolute frequencies and percentages for qualitative variables. For the comparison of VAS values and drug consumption, we used the Mann–Whitney U test. For demographic data, clinical features, reported opioid side effects, and adverse events, we compared the proportions of patients per group. For the comparison of patients with BFI ≥ 60, we used the chi-square test to evaluate relative frequencies. All tests were two-sided with a significance level set at 5%.® for Windows, version 5.01 .Statistical analysis was performed using MedCalc for Windows, version 11.3.0.0  and GraphPad PrismData from 53 patients receiving an opioid treatment for at least 2 years and regularly attending the scheduled follow-up visits were extracted: among these, 27 received the drug combination , and 26 received Oxycodone only . The subdivision of data sets into two groups  was made for analysis purposes, only. Data gathering was extended up to 2 years of follow-up time, during which five patients dropped out of the OXN group  and five patients dropped out of the OXY group . Final analysis included 43 patients: 21 patients receiving oxycodone only (OXY group) and 22 patients receiving both oxycodone and naloxone (OXN group). The OXY group and the OXN group were similar for demographic data and baseline clinical features . PatientOpioid requirements during the study period are shown in It is important to stress the fact that all 43 patients reached and maintained the targeted pain relief of 30% in terms of VAS reduction versus baseline, as shown in This study demonstrated that patients treated with oxycodone-naloxone reached the same pain relief as the ones receiving oxycodone only. However, the patients in the OXN group required lower opioid doses at 18 and 24 months to maintain the same pain relief as those in the OXY group. Moreover, the OXN group had a significantly lower incidence of constipation at 18 and 24 months.The latter results were already well known in the literature ,45,46,47The use of opioid antagonists to decrease the development of opioid tolerance as well as their side effects while preserving opioid analgesia is an attractive concept. Recent evidence in rodents indicates that the co-administration of ultralow doses of opioid antagonists with opioid agonists can decrease or block the development of opioid tolerance ,37,38,39In this study, we observed that the incidence of therapy dropouts was similar in the OXY and the OXN groups. In the OXN group, no patients dropped out of the treatment schedule due to excessive constipation, in contrast from patients in the OXY group, providing further evidence that the co-administration of naloxone and oxycodone has a minor impact on bowel function also in the long term. Of great interest is that none of the patients developed opioid abuse while following the treatment schedule. In our opinion, this is mainly due to the careful selection of candidates for chronic opioid therapy that we routinely perform in our Pain Relief Center.This study has several limitations. The most important is the reduced number of patients. This was due to the strict protocol we routinely apply at our center ahead of patient selection for long-term opioid treatment. Moreover, it was not possible to clarify why patients had received either oxycodone-naloxone or oxycodone only, but the number of patients receiving either therapy was similar, providing the possibility to compare the results. A further limitation could be that the sample primarily comprised Caucasian patients. It is possible, though unlikely, that co-treatment of pain with oxycodone and naloxone may have different effects in other ethnicities. Moreover, the additional administration of non-opioid analgesics was not standardized. It is possible that these drugs influenced the pain scores among the two treatment groups. However, none of the patients underwent modifications of the non-opioid analgesic therapy during the period of time covered by the study.The strengths of this study include a long, standardized follow-up period (2 years), a homogeneous population  and an evenly distributed rate of dropouts  between the two analyzed groups . Importantly, we aimed to achieve feasible and stable pain relief for our patients, and this enabled us to affirm that the addition of naloxone to oxycodone reduced the development of opioid tolerance and the incidence of OIBD in the long term.p-value 0.0142 at 18 months, p-value 0.0052 at 24 months).In our cohort, the drug consumption over time to reach and maintain the targeted 30% pain relief was significantly different between the two groups, and this significance grew stronger with time (In conclusion, this is the first real-life and long-term study providing evidence that the oxycodone-naloxone combination may inhibit the development of opioid tolerance in chronic low back pain due to osteoarthritis. Further studies with prospective designs and randomization are needed to better clarify the mechanism of this phenomenon.


Correction to: BMC Musculoskelet Disord 23, 156 (2022)https://doi.org/10.1186/s12891-022-05097-zi)movement time and increased number of errors during head aiming tasks in neck pain patients when compared to control subjects: as indeed the number of errors was increased across all neck pain patients (both idiopathic and whiplash associated neck pain) with a strong level of evidence, the strong level of evidence for an increase in movement time was only found in idiopathic neck pain patients. Results in whiplash associated neck pain patients regarding movement time were inconsistent, as the authors described in detail in the result and conclusion section of the main text.The authors would like to correct and precise their statement in the results section of the abstract regarding increased ii)mean velocity, peak acceleration, reaction time, point deviation and time on target during head aiming tasks, but these alterations implied on one hand a decrease , whereas on the other hand an increase (reaction time and point deviation), as correctly described in detail in the results and conclusion section of the main text.The authors noted that an imprecision occurred in summarizing results in the abstract section leading to a potential misinterpretation of the results by the readers : indeed moderate evidence was found in whiplash associated neck pain patients for altered iii)The authors would like to add a correction to Table 4 : the samples of Yang et al  and ZhouFollowing publication of this  article,The original article  has been


This study aimed to explore the predictive value of the HEART score combined with hypersensitive C-reactive protein (hs-CRP) for 30 d major adverse cardiovascular events (MACEs) in patients with acute chest pain.  103 patients with acute chest pain admitted to the emergency department of our hospital from May 2020 to May 2022 were selected as the study subjects. The patients' HEART score and plasma hs-CRP level were recorded. The patients were followed up for 30 d to observe whether MACE occurred. P < 0.05). The age, HEART score, and hs-CRP levels of patients in the MACE group were higher than those in the non-MACE group (P < 0.05). The HEART score and the hs-CRP level were independent risk factors for 30 d MACE in patients with acute chest pain (P < 0.05). The AUC of the HEART score combined with hs-CRP in the occurrence of 30 d MACE in patients with acute chest pain was 0.901, which was significantly higher than 0.720 and 0.758 of single detection.  Among 103 patients with acute chest pain, MACE occurred in 8 cases within 30 d of follow-up, and the probability of MACE was 7.76%. There was a statistically significant difference in 30 d MACE risk among patients with different HEART score stratification ( The HEART score combined with hs-CRP can better predict the occurrence of 30 d MACE in patients with acute chest pain. Acute chest pain is a clinical emergency, and its incidence accounts for 5%–20% of patients in emergency medicine and even 20%–30% in large tertiary hospitals . Acute cIn order to quickly differentiate between chest pain categories and assess the degree of risk, emergency physicians in China and abroad have developed many acute chest pain scoring systems to make accurate treatment decisions and improve patients' quality of life as early as possible , 8. The At present, there are few clinical studies on the predictive value of the HEART score combined with hs-CRP on 30 d MACE in patients. Therefore, in this study, 103 patients with acute chest pain were selected to observe the occurrence of 30 d MACE and to analyze the relationship between the HEART score, hs-CRP, and MACE.103 patients with acute chest pain admitted to the emergency department of our hospital from May 2020 to May 2022 were selected as the study subjects. Inclusion criteria were as follows: presented with chest pain as the main symptom; chest pain onset within 12 h; age ≥ 18 years; complete medical records and able to complete follow-up. Exclusion criteria were as follows: chest pain caused by trauma; systemic pain due to rheumatic diseases involving the chest; liver and kidney insufficiency; combined with malignant tumors, infectious diseases or psychiatric diseases; a recent history of heart valve disease, cardiomyopathy, myocarditis, etc.n = 20), 4∼6 points being the moderate-risk group (n = 44), and 7∼10 points being the high-risk group (n = 39). The HEART scoring system is shown in All patients were treated symptomatically on admission according to their condition. ① After admission, a risk score was assigned to all enrolled patients based on the HEART scoring system. The total score was 10 points, with 0∼3 points being the low-risk group , as shown in There was a statistically significant difference in 30 d MACE risk among patients with different HEART score stratification (P < 0.05). There was no statistically significant difference between the remaining clinical information of the two groups (P > 0.05), as shown in The age, HEART score, and hs-CRP levels of patients in the MACE group were higher than those in the non-MACE group (P < 0.05), as shown in Multifactorial logistic analysis showed that the HEART score and the hs-CRP level were independent risk factors for 30 d MACE in patients with acute chest pain (The AUC of the HEART score in predicting 30 d MACE in patients with acute chest pain was 0.720. The AUC of hs-CRP in predicting 30 d MACE in patients with acute chest pain was 0.758. The AUC of the HEART score combined with hs-CRP in predicting 30 d MACE in patients with acute chest pain was 0.901, as shown in Acute chest pain is one of the more dangerous diseases in the emergency department and is a pain that occurs in the chest or radiates from other parts of the body to the chest . The cauThe HEART score is a nonspecific scoring system that does not require inclusion or exclusion criteria for patients with chest pain, and the items of the score are easy to collect data and less difficult to calculate, which facilitates daily use by clinical workers . Unlike It has been reported that the occurrence of acute cardiogenic chest pain is closely related to the body's inflammatory response and coagulation formation . As an iOnly troponin is included in the HEART scoring system, which shows poor specificity. Therefore, the addition of another biomarker above the cardiac score has a positive effect on improving the evaluation of acute chest pain. In addition, hs-CRP has good specificity but relatively poor sensitivity, and the predictive value of a single test is not high, so it has good significance to combine the two. In view of the limitations of the HEART score and hs-CRP alone in predicting the short-term prognosis, we applied the combination of the HEART score and hs-CRP in prognostic assessment. The AUC of the HEART score combined with hs-CRP in the occurrence of 30 d MACE in patients with acute chest pain was 0.901, which was significantly higher than 0.720 and 0.758 of single detection. This revealed that the HEART score combined with hs-CRP could better predict the occurrence of 30 d MACE in patients with acute chest pain and can improve sensitivity and specificity.In conclusion, the HEART score combined with hs-CRP can better predict the occurrence of 30 d MACE in patients with acute chest pain, which is helpful for assisting clinical treatment decision-making.


Pain is a common symptom in palliative care cancer patients and is often insufficiently relieved. In recent years, transcranial direct-current stimulation (tDCS) of the motor cortex has been shown to be effective to treat chronic pain, essentially neuropathic pain. We propose to test the efficacy of tDCS in patients experiencing cancer pain in the palliative care setting.This article describes the protocol of a bicentre, randomized, parallel-arm, sham-controlled clinical trial evaluating tDCS in the treatment of palliative care patients with refractory cancer pain. Seventy patients between the ages of 18 and 80 years experiencing refractory pain with a pain score of 4/10 on a numerical rating scale (NRS) ranging from 0 to 10 will be enrolled in this trial. The main exclusion criteria are patients unable to fill in the various rating scales and life expectancy less than 3 weeks. Treatment consists of 5 consecutive tDCS sessions targeting the motor cortex (one daily session for 5 days) on the contralateral side to the pain. After randomization (1:1 ratio), 35 patients will receive active stimulation and 35 patients will receive sham stimulation. The primary endpoint is the NRS score and the primary objective is a significant improvement of this score between the baseline score recorded between D-3 and D-1 and the score recorded 4 days after stopping treatment (D8). The secondary objectives are to evaluate whether this improvement is maintained 16 days after stopping treatment (D21) and whether the following scores are improved on D14 and D21: Brief Pain Inventory, Edmonton Symptom Assessment System, Hospital Anxiety and Depression scale, State-Trait Anxiety Inventory and Medication Quantification Scale.Positive results of this trial would indicate that tDCS can improve pain and quality of life of cancer patients in the palliative care setting. Reduction of analgesic consumption and improvement of activities of daily living should allow many patients to return home with a decreased workload for caregivers. Pain is a common symptom in palliative care cancer patients and is often insufficiently relieved , 2. The In recent years, noninvasive brain stimulation (NIBS) techniques  or transcranial direct-current stimulation (tDCS)) have been successfully used to treat chronic pain . We havetDCS appears to be more suitable than rTMS for the treatment of palliative care patients, who are often difficult to mobilize, as tDCS can be delivered at the patient’s bedside and possibly even at home, which is not the case with rTMS. tDCS also appears to be rapidly effective (after 5 sessions) in the context of cancer pain, and this effect lasts longer than that of rTMS.The proposed treatment of refractory cancer pain by tDCS in palliative care patients is a new treatment modality that is well adapted to hospitalised patients. Each patient will receive 20 minutes of transcranial direct-current stimulation daily for 5 consecutive days. One arm will receive active stimulation and the control arm will receive sham stimulation. Patients and investigators will be blinded to the type of tDCS. By improving the patient’s activities of daily living, this treatment will enable the patient to return home under good conditions for both the patient and the caregivers. This treatment can also be continued at home. This strategy is consistent with current guidelines in this field, in which the priorities are improvement of quality of life , return tDCS was tested in healthy subjects from 2000 until 2005, at the time of the first clinical applications in the treatment of chronic pain. tDCS consists of delivering a low-intensity (1 to 2 mA) direct electrical current by means of a pair of electrodes (anode and cathode) applied to the scalp. Electrodes generally have a diameter (round electrode) or a diagonal (rectangular electrodes) ranging from 2 to 3.5 cm. To stimulate a given cortical zone, the anode is placed over of the selected zone, generally identified by means of an EEG headset (10/20 System Positioning). For the treatment of pain, the anode is placed over the primary motor cortex (M1) on the contralateral side to the pain or on the left side in patients with diffuse pain. The cathode is placed over a supposedly neutral cortical zone, usually the contralateral supraorbital cortex with respect to the anode. In this study, the stimulation intensity will be 2 mA using round sponge electrodes 3.5 cm in diameter. As in the case of rTMS, stimulation of M1 is thought to be active by means of the connections between the motor cortex and numerous structures situated away from M1 involved in pain modulation : especiaA tDCS session generally lasts 20 minutes. The patient may experience a feeling of heat or paraesthesia at the site of the electrodes for the first 30 seconds, but subsequently does not experience any sensations, which is why active stimulation will be delivered for the first 30 seconds of the sham procedure . In thisThis study will be conducted in patients hospitalised in a unit experienced in palliative care. tDCS will be delivered daily for 5 consecutive days (from Monday to Friday) with the patient either sitting or lying down.At the individual level, pain intensity is expected to decrease by the 2nd or 3rd tDCS session, with a more marked improvement after the 5th session. This improvement is expected to last at least 4 days (D8) and up to 16 days (D21) , 18. It , especially in the event of excessive stimulation (> 2 mA) delivered by excessively small electrodes (< 20 × 20 mm) [Side effects are recorded in the electronic observation booklet after each tDCS session  and during the 3 subsequent evaluations . Side effects  such as × 20 mm) . At the A significant collective benefit could be observed, and tDCS could markedly decrease the length of hospital stay of these patients and their analgesic drug consumption and should therefore have a significant health economics impact. In parallel, the patient’s and caregivers’ quality of life could be significantly improved. In the longer term, continuation of tDCS at home would require a new organization. The development of remote treatment techniques must also be considered .More generally, this protocol raises the issue of clinical research in palliative care patients , which hIn order not to penalize patients in the placebo group, it is planned to lift the blind at D21 and to offer these patients the active treatment outside the protocol. Patients who have been actively treated and whose pain has recurred after D21 will be offered a second treatment outside the protocol.As tDCS is a noninvasive technique with few expected adverse effects, the benefit/risk balance is expected to be highly positive for the patient in this context of refractory cancer pain in the palliative care setting.This study is designed to evaluate the analgesic efficacy of 5 consecutive tDCS sessions to the primary motor cortex in patients with cancer pain in the palliative care setting.The primary endpoint is the score of the numerical rating scale (NRS), which measures pain intensity on a scale from 0 to 10 . The meaImmediate impact of each tDCS session on pain intensity.Response rate at the end of treatment.Residual analgesic effect.Effects of TDCS on the other main symptoms likely to impair quality of life.Analgesic consumption on D0 and D8.The secondary objectives will be to evaluate:Pain NRS score, MQS , includPain NRS scores, recorded before and after each session.Efficacy of treatment, defined by a ≥ 20% reduction of the mean NRS score between D0 and D8 (IMMPACT recommendation in chronic pain ).Mean NRS score on D14 and D21 in the 2 arms.. BPI .. ESAS (Edmonton Symptom Assessment System) .. HADS  .. STAI-Y (State-Trait Anxiety Inventory (Form Y) ).Completion of the following questionnaires and scales on D0 and D8:Analgesic consumption assessed by MQS on D0 and D8.Secondary endpoints will be:Analysis of repeated measurements of quantitative secondary endpoints  will be based on the mean variations of the endpoint between the baseline assessment (D0) and the D21 assessment.This is a French bicentre , randomized, comparative, double-blind, sham-controlled trial conducted in two parallel arms: tDCS (35 patients) and sham tDCS (35 patients).Centralized randomization will be performed by software and will be specific to each of the 2 centres. Patients will not be informed about whether they have been allocated to the active tDCS arm or the sham tDCS arm. Physicians performing the tDCS technique and the evaluating physicians will also be blinded to the type of treatment delivered (see “Interventions: tDCS and follow-up intervention”).Doses of analgesic medications  must be stable for at least 48 hours  prior to inclusion in the study. The level of analgesic treatment will be assessed by MQS. Analgesic doses may be able to be decreased from the first day of tDCS depending on its analgesic effect. One of the objectives of tDCS is to decrease the doses of analgesics in order to avoid a state of drowsiness or torpor associated with impaired quality of life.Patients between the ages of 18 to 80 years with cancer pain refractory to medical treatment (mean NRS ≥ 4/10 on 2 consecutive days) in the palliative care setting.Patients agreeing to participate in a research protocol in this palliative care setting.Patients younger than 18 years or older than 80 years.NRS < 4/10 .Patients unable to fill in the various questionnaires, specifically chosen to be simple and easy to fill in.Patients refusing to sign the informed consent form.Patients with cognitive impairment, metal implantation in the brain and mood disordersPatients with a life expectancy less than 3 weeks (duration of study follow-up).Patients will be recruited from the Center 1 , and Center 2 . The inclusion of one patient per month corresponds to the recruitment, treatment and follow-up capacities of each of these centres in accordance with the protocol. The study will last 24 months.Verification of inclusion and exclusion criteria. Patients will be provided with the information sheet and will be asked to sign the informed consent form. The patient will be provided with NRS forms (3 assessments per day for 48 hours). For organizational reasons, this screening visit will be held on a Friday. NRS scores will be recorded on Saturday and Sunday so that inclusion or exclusion of the patient can be decided on Monday.Recording of NRS scores for 48 hours (D-3 to D-1) allowing inclusion of the patient. Recording of clinical parameters such as age, sex, weight, height, etc., medical history, previous and concomitant treatments, vital signs. Baseline assessment: NRS, BPI, ESAS, HADS, STAI-Y and MQS (see secondary endpoints). Randomization . Study personnel  will be blinded to the results of randomization.Study personnel (physician or trained nurse), but not the patient, will be informed about the results of randomization. tDCS will be delivered daily for 5 consecutive days. The NRS will be scored 3 times a day on these 5 days from Monday to Friday.Review of adverse events (AEs), recording of NRS scores and the various other assessment scores  4 days after stopping treatment.The same parameters as those assessed on D8 will be assessed at these visits. These parameters will reflect the patient’s state 9 days and 16 days after stopping treatment. Patients who have returned home in the meantime will be assessed at home. In every case, the assessment will be performed by a team blinded to randomization Table In order to maximize the number of patients evaluable for the primary analysis on the mITT population (modified intention-to-treat ), in theThe pain numerical rating scale (NRS) is a pain self-assessment tool. The patient rates his or her pain orally on a scale from 0 to 10, where 0 corresponds to the lower limit defining absence of pain and 10 corresponds to the upper limit defining the worst imaginable pain. The NRS was preferred to a VAS  based on the 2009 expert consensus on cancer pain assessment .This scale can be used to include patients considered to experience sufficiently severe pain to justify more or less invasive treatment. For example, pain scored as 3/10 corresponds to moderate pain , 46, whiThe Brief Pain Inventory (BPI) is a self-administered questionnaire constructed and tested in cancer pain . It explThe validity and reliability of the NRS for the evaluation of the efficacy of analgesic treatment has been established . A 20 toEvaluation of the various symptoms observed in the context of palliative care constitutes an evaluation of the quality-of-life approach in this setting. The Edmonton Symptom Assessment System (ESAS) has been validated and found to be one of the most reliable of the various scales . This scSince 1983, anxiety and depression are generally evaluated by the HADS . The HAThe STAI-Y  is a selThe short form, composed of 9 items, has been validated and shown to be reliable in the assessment of cancer pain . The BPIvery high > 65,high: 56 to 65,moderate: 46 to 55,low: 36 to 45,very low ≤35.Scores range from 20 to 80 and are classified in the following way:The Medication Quantification Scale (MQS) is a scale used to quantitatively evaluate changes in analgesic drug administration . Each meTo date, this scale has not been validated for the evaluation of cancer pain, nor in the context of palliative care. As much as an improvement of a possible depressive state could be explained by the action of the tDCS , it is nStatistical justification of the sample size: a 2-point improvement of the numerical rating scale is considered to be clinically relevant , which iAs this is the first protocol dedicated to the treatment of painful patients in a palliative care setting with tDCS, we did not find any evidence in the literature that could help us justify the number of needed patients for the evaluation of the other clinical parameters, apart from the NRS.A mean NRS difference of 2 points between the active tDCS arm and the sham tDCS arm,Standard deviation of 2.8,Power of 80%.Alpha risk of 5%,On the basis of these hypotheses:32 patients per arm would be necessary, i.e. a total of 64 patients. In order to ensure sufficient power, an additional 10% of patients will be included in the study, i.e. a total of 70 patients.The study will therefore include 70 patients: 35 in the tDCS arm and 35 in the sham tDCS arm.The variables measured on inclusion will be described for all patients and in each of the two arms by number and percentage for each modality for qualitative variables and by minimum, maximum, mean, standard deviation and quartiles for quantitative variables. The primary efficacy population will be a modified intention-to treat (mITT) population, comprising all randomized patients who have received at least one tDCS session (active or sham) and who were evaluated on D0 (baseline) and on D8.Analysis of the primary endpoint, the pain NRS, will be performed on the mITT population.The mean NRS score on D8 will be compared between the active tDCS arm and the sham tDCS arm using a mixed linear model in order to take stratification factors into account.The mean NRS score on D8 will be compared between the active tDCS arm and the sham tDCS arm using a mixed linear model in order to take stratification factors into account. This analysis will also be adjusted for analgesic consumption based on the MQS score.The immediate efficacy of tDCS on pain intensity will be compared between the two arms using a mixed linear model with the pre- and post-tDCS difference of the NRS score as the variable to be explained. This model will take repeated measures per patient into account.The response rate will be compared between the two arms by a mixed logistic model in order to take stratification factors into account.The residual analgesic effect on D14 and D21 will be studied using a mixed linear model in order to take stratification factors into account. This analysis will also be adjusted for analgesic consumption.The course of quality of life assessed by the BPI, ESAS, HADS and STAI-Y between D0 and D7 will be compared between the two arms by a mixed linear model in order to take stratification factors into account.Analgesic consumption, evaluated by the MQS questionnaire, will be compared between the two arms using a mixed linear model.Complementary analysis of the primary efficacy endpoint could be conducted on a per protocol population including all patients of the mITT population not presenting any major protocol violations. These major violations will be defined in the analysis plan before locking the database.Centralized randomization will be performed on D0 after verification of the inclusion criteria. Randomization will be performed under double-blind conditions and will be stratified according to the mean baseline pain intensity (4–6 or 7) over the last 48 hours before inclusion and according to centre.https://fr.ennov.com/getions-essais-cliniques/) by logging onto the website: https://nantes-lrsy.hugo-online.fr/CSOnline/ after obtaining the patient’s informed consent on D0. The inclusion number and randomization arm will be automatically allocated at the time of randomization. A confirmation e-mail will be sent to the person who performed randomization and to all other people concerned.Patients will be randomized to receive either active tDCS or sham tDCS for the 5 treatment days defined by the protocol. The randomization ratio will be 1:1. Randomization will be stratified by centre by means of the Ennov Clinical electronic CRF (Randomization lists will be established by a Nantes university hospital research promotion department statistician.A patient registered in the trial, to whom treatment has been allocated and documented, will be considered to be randomized. A patient cannot be included, evaluated or randomized in the trial more than once.The effect of motor cortex tDCS on cancer pain and its duration of action are important parameters that need to be assessed in order to define the optimal modalities of application of tDCS in the palliative care setting.Up until now, the principle of neurostimulation techniques has been mainly based on the Gate Control theory elaborated by Melzack and Wall  to treatThe origin of pain does not appear to affect the result. The main results concern visceral pain , 18, butThe other treatments that can be proposed instead of tDCS often have the disadvantage of being administered by infusion and/or of causing disorders of consciousness. Sedation is in some cases a desired effect , but it One of the limitations of this protocol is the lack of a pilot study, which led us to make choices that were not always well documented in the development of the protocol. The first choice was to select the tDCS system best suited for a double-blind treatment protocol in a palliative care setting. There are now several devices available that meet these criteria well. The HDC Kit makes it easy to perform double-blind stimulation easily at the patient’s bed. The calculation of the number of patients could not be based on similar protocols. Those dedicated to cancer pain , 18 wereWe hope that this protocol will be able to confirm the value of tDCS in the treatment of cancer pain in palliative care patients, especially by facilitating a rapid return home.