Biliary colic (BC) is a frequent hepatobiliary disorder encountered in emergency departments. Acupuncture may be effective as an alternative and complementary medicine for BC. Nonetheless, rigorous trials investigating its efficacy are lacking. Therefore, the aim of this study protocol is to determine whether acupuncture provides immediate relief of pain and associated symptoms in BC patients.Eighty-six participants who aged from 18 to 60 years with BC will be recruited in the First People's Hospital of Longquanyi District, Chengdu . All participants will be allocated into two treatment groups including acupuncture group and sham acupuncture group using a 1:1 ratio. Each group will only receive a single 30-min needle treatment while waiting for their test results after completing the routine examination for BC. The primary outcome of the study is to assess the change in pain intensity after the 30-min acupuncture treatment. The secondary outcomes of the study include the change in pain intensity at various time points, the degree of gastrointestinal symptoms at different time points, the level of anxiety experienced during pain episodes at different time points, the score of Pain Anxiety Symptoms Scale-20 (PASS-20), the score of Fear of Pain Questionnaire-III (FPQ-III), and the score of Pain Catastrophizing Scale (PCS), among others.The results of this research will provide substantial evidence regarding the efficacy of acupuncture in alleviating symptoms associated with BC.ClinicalTrials.gov, ChiCTR2300070661. Registered on 19 April 2023.The online version contains supplementary material available at 10.1186/s12906-023-04030-8. Biliary Colic (BC) is a symptom of an acute attack of gallstones. The prevalence of gallstones has been displayed to be 10%-20% patients in worldwide. Furthermore, more than 20% of patients with gallstones will develop BC symptom .The affective component of pain includes feelings of distress, sadness, anxiety, and depression in response to noxious stimuli . DepressAn evidence-based clinical practice guideline for the remission of BC has recommended non-steroidal anti-inflammatory drugs (such as diclofenac and indomethacin), spasmolytics (such as butylscopolamine), opioids (such as buprenorphine), and cholecystectomy (within 24 h after the diagnosis of biliary colic) –11. HoweAcupuncture, as part of traditional Chinese medicine, potentially relieves the pain-related disorders –22. SomeHence, a randomized, sham-controlled trial will be conducted to assess the potential of acupuncture in improving pain and related symptoms of BC.https://www.chictr.org.cn/). The trial will be performed in accordance with the Standard Protocol Items: Recommendations for Interventional Trials The single center, sham-controlled, blinded, randomized trial of acupuncture treatment for BC will be executed in the First People's Hospital of Longquanyi District of Chengdu  from May 2023 to July 2024. The protocol of trial has been approved by the Affiliated Hospital of Chengdu University of Traditional Chinese Medicine (No. 2023KL-008). And it has been registered with an identifier (ChiCTR2300070661) at ClinicalTrials.gov . All patients will be screened by Specialists and acupuncturists according to the diagnostic criteria from the Recommendations for EASL clinical practice guidelines on the prevention, diagnosis and therapy of gallstones (2016) .Participants who meet the following inclusion criteria will be eligible for the study: (i) those who meet the diagnostic criteria; (ii) mild tenderness in the right upper quadrant, negative or positive Murphy's sign; (iii) a numerical rating scale (NRS) score of ≥ 3 points; (iv) BC patients aged between 18 to 60 years, without any gender restrictions; (v) gallbladder stones demonstrated by radiology or ultrasonography; (vi) no history of acupuncture treatment within the past month; (vii) not participating in any other clinical studies; and (viii) willing to voluntarily sign the informed consent form.Participants who meet the following exclusion criteria will be excluded from the study: (i) a history of jaundice; (ii) presence of bile duct stones, acute cholecystitis, acute suppurative cholecystitis, gangrenous cholecystitis, incarcerated cholecystitis, gallbladder perforation with diffuse peritonitis, or BC complicated with acute pancreatitis; (iii) administration of analgesics such as antispasmodic, non-steroidal anti-inflammatory drugs, or choleretic before acupuncture; (iv) presence of serious complications or primary diseases involving the brain, cardiovascular, liver, kidney, endocrine, or hematopoietic systems; (v) presence of serious digestive system diseases, such as peptic ulcer, upper gastrointestinal bleeding, gastric tumor, Crohn's disease, irritable bowel syndrome, etc.; and (vi) participation in other clinical trials within the last three months.BC patients in emergency department of the First People's Hospital of Longquanyi District  will be diagnosed by emergency physician. Simultaneously, researchers will be responsible for the screening and presenting the inclusion criterion, the operational and allocated details of intervention (acupuncture group and sham acupuncture group), and the potential risks of this trial. All subjects will have the right to withdraw from the trial at any time. Additionally, all subjects will be required to sign an informed consent form before the trial commences.Baseline evaluation will be conducted for eligible subjects. The random sequence will be generated using SAS® 9.4 software . The random sequence will be recorded on sealed and opaque envelopes, with the random numbers of the two groups inside. Moreover, these envelopes will be opened sequentially by a researcher assistant who is not involved in the data collection or acupuncture treatment. In addition, the researcher assistant will randomly assign the subjects to the acupuncture group and the sham acupuncture group with ratio of 1:1.The researcher assistants, outcome assessors, statisticians and subjects will be blinded to the group assignment. All subjects will receive acupuncture treatment lying on the bed in a quiet clinic. The control group will use a non-penetrating sham apparatus, similar in appearance to acupuncture needles, to achieve blinding. Furthermore, all subjects will be asked about their experience after the acupuncture session to assess whether they have been successfully blinded.Yanglingquan (GB34) is acupoint of the gallbladder meridian of foot-shaoyang (GB), which is frequently used for Biliary disease , 29. TheThe right non-acupuncture point located at the lateral edge of the tibia, approximately 1–2 cm away from Zusanli (ST36), will be selected as the sham point . A non-pThe primary endpoint is the change of pain intensity from baseline to 30 min after acupuncture by evaluating the NRS. The NRS is a 10-point scale, with zero representing "no pain" and 10 representing "worst possible pain". The pain intensity of BC subjects will be presented by marking a “√” on the line of NRS.The secondary end points will be evaluated as following:i)The pain intensity will be assessed the change of NRS score from baseline to the 10 min, 20 min and 40 min after needle manipulation.ii)The degree of gastrointestinal symptoms, such as nausea, vomiting and pantothenic acid, will be evaluated for change from baseline by the visual analogue scale (VAS) at 10 min, 20 min, 30 min and 40 min after needle manipulation .iii)The level of anxiety during episodes of pain will be measured by changes in the VAS at 10 min, 20 min and 30 min after needle manipulation, compared to baseline . The VASiv)The pain-related emotional responses, such as anxiety and fear, will be assessed using the Pain Anxiety Symptoms Scale-20 (PASS-20), the Fear of Pain Questionnaire-III (FPQ-III), and the Pain Catastrophizing Scale (PCS) at baseline –37. The v)The patients' anticipated responses to acupuncture will be evaluated using the Acupuncture Expectancy Scale (AES) at baseline .vi)The patient’s satisfaction for acupuncture will be monitored by the 5-point Likert scale at 30 min after needle manipulation .vii)The evaluation of needle sensation will be conducted using the Chinese version of the modified Massachusetts General Hospital Acupuncture Sensation Scale (C-MASS) at 10 min, 20 min and 30 min after needle manipulation .viii)The use of rescue analgesia will be recorded 10 min after the completion of acupuncture. The recurrence rate of BC and any adverse events occurring within 72 h after needle manipulation will be obtained through a telephone follow-up.The information of adverse events (AEs) related to interventions including infection, bloody swelling, stabbing pain, broken needle, hemorrhage, palpitation, syncope, headache will be monitored and recorded in the case report forms (CRF) by a research assistant. Serious AEs will be handled by emergency medicine physicians or acupuncturists. Moreover, serious AEs will be reported to the Ethics Committee of Hospital of Chengdu University of Traditional Chinese medicine.The data will be collected alone on CRF by the same evaluator and will be imported into the computer respectively by two research assistants who are not involved in the trial to avoid bias in the results. All personnel involved in the study will be required to complete professional training to ensure the quality of the trial. This training will cover details of the trial, including the introduction of inclusion and exclusion criteria, completion of CRF, acupuncture procedures, and data entry methods.The primary outcome of this study is the mean difference in NRS scores for BC between the baseline and the endpoint. Sample size calculations will be based on a previous neuroimaging study of acupuncture in BC , which rThe independent samples t-test or Wilcoxon rank-sum test will be used to analyze continuous variables in the demographic characteristics of the two groups, based on their normality. Categorical variables in the demographic characteristics will be analyzed using chi-squared or Fisher's exact tests. If there is a significant difference in demographic characteristics such as age, gender, and family history, they will be included as covariates in the efficacy analysis. The analysis will include all randomized BC patients based on the intention-to-treat (ITT) principle. Subgroup and sensitivity analyses may also be performed.The change of pain intensity from baseline to 30 min after acupuncture will be analyzed by using analysis of covariance with acupuncture group and sham acupuncture treatment as factors and baseline pain intensity as a covariate. Repeated measures ANOVA will be used to assess the difference in the secondary outcomes at different time points. The degree of patients’ expectations and satisfaction with acupuncture will be evaluated using linear regression.BC is one of the 64 diseases that are suitable for acupuncture treatment, as recommended by the World Health Organization . The stuSeveral clinical studies have proposed that acupuncture on GB34 could significantly improve the symptoms of patients with BC , 51. FurIn this trial, there are several limitations that need to be acknowledged. Firstly, blinding of acupuncturists is not possible due to the unique nature of acupuncture procedures. Secondly, the small sample size may lead to inconclusive results. Finally, there is a potential for a relatively high dropout rate in the sham acupuncture group.To summarize, this trial aims to investigate the efficacy and safety of acupuncture in relieving pain and pain-related symptoms in patients with BC by controlling the quality of acupuncturist’s operation and implementing assignment blinding. The results of this trial are expected to provide an alternative treatment option for patients with BC and contribute to the development of guideline recommendations.The trial is currently recruiting participants. The first subject has not been recruited so far and the investigators are still collecting.Additional file 1.


Background In the UK, diagnostic delays remain a challenge in axial spondyloarthritis (axSpA). Studies have shown that acute anterior uveitis is the most common extra-articular manifestation associated with axSpA. As part of a National Axial Spondyloarthritis Society (NASS) Aspiring to Excellence quality improvement project, this study aimed to ascertain the burden of inflammatory back pain (IBP) in patients attending a uveitis clinic and to establish the number of these patients who had not been referred to a rheumatologist, thereby contributing to the diagnostic delay. The secondary aims were to explore the factors contributing to the diagnostic delay.Methods A 22-question patient survey was created to identify the burden of back pain in patients attending a specialist uveitis clinic at a London NHS Trust. Participants were recruited when attending their clinic appointments. Survey content included patient demographics and whether they had experienced back pain for longer than three months. The Berlin Criteria was used to identify the presence of inflammatory back pain, and it was also ascertained whether participants had a previous diagnosis of axSpA. Participants were asked if they had seen any healthcare professionals regarding their back pain and the total number of consultations they had had with each profession.Results A cohort of 50 patients who attended the uveitis clinic at the Royal Free London NHS Trust completed the survey between February and July 2022.The mean age of the respondents was 52 years with a mean length of time with uveitis of 6.57 years. Of them, 64% were female and 36% were male. Forty per cent (40%) of participants (20 respondents) reported experiencing back pain for more than three months and 12% (six respondents) had a diagnosis of axSpA.Of those who reported back pain for more than three months, the mean age of onset of back pain was 28.6 years. Of the 14 participants (28%) who had back pain and were not diagnosed with axSpA, nine (18%) fulfilled the Berlin criteria for IBP.All participants had seen a GP or allied health professional specifically for their back pain. On average, respondents had seen two allied healthcare professionals, but only 40% (eight) of respondents with back pain had been seen by a rheumatologist.Conclusions In this study, the data highlights that inflammatory back pain is common in patients with uveitis and the majority of patients with inflammatory back pain had not been referred to a rheumatology service and potentially have undiagnosed axSpA. Contributing factors to this potential delay in diagnosis include a lack of awareness of axSpA and its presenting features and associated conditions and a lack of onward referral for a specialist rheumatology opinion. This highlights the need for public, patient and healthcare professional education and the development of timely referral pathways to reduce delays in diagnosis. Introduction In the United Kingdom, there is an 8.65-year delay in the diagnosis of axial spondyloarthritis (axSpA) . This deAcute anterior uveitis is the most common extra-articular manifestation associated with axSpA, occurring in 25-35% of patients . The aimA prospective analysis was undertaken of patients in a London NHS trust from February to July 2022. Participants were recruited following attendance at the uveitis clinic. After an explanation of the aim of the survey, verbal consent was taken, and a 22-question survey was completed. The survey included patient demographics, the length of time they had had uveitis and whether participants had previously been diagnosed with axSpA. The survey established whether participants were currently taking or had previously taken a biologic medication. Participants were asked if they had experienced back pain lasting over three months, and if so, their age at symptom onset, the location of symptoms and whether their symptoms improved with non-steroidal anti-inflammatory medication. The presence of IBP was identified using the Berlin Criteria. The Berlin Criteria confirms IBP in individuals that have experienced back pain for more than three months, are under the age of 50 years and fulfil at least two of the following criteria: morning stiffness >30 minutes, improvement of back pain with exercise but not rest, nocturnal awakening during the second half of the night and alternating buttock pain . The full questionnaire is detailed in the Appendices.A total of 121 patients were approached, of which 50 consented to complete the survey. Forty per cent (40%) of participants (20) reported that they had experienced back pain for more than three months. Twelve per cent (12%) of participants (6) had an established diagnosis of axSpA. Participant demographics and key results are presented in Table Of the remaining 14 participants 28%) who had back pain and were not diagnosed with axSpA, six females (12%) and three males (6%) fulfilled the Berlin Criteria for IBP (Table 8% who haOnly eight of the 20 respondents that had experienced back pain for longer than three months had seen a rheumatologist. Figure Acute anterior uveitis is the most common extra-articular manifestation associated with axSpA, occurring in 25-35% of patients . StudiesBarnett et al. explored the reasons for the delay in diagnosis of axSpA and highlighted that a lack of referrals to rheumatologists, from both primary and secondary care services, played a significant role . Our resFurther work must also be carried out to improve awareness of axSpA in secondary care and to simplify internal referral pathways. The DUET study carried out by Haroon et al. concluded that approximately 40% of patients presenting to an ophthalmology hospital emergency department with anterior uveitis had undiagnosed SpA, which supports the results of our study . RademacLimitations The major limitation of this study was the small sample due to difficulties in recruiting participants who had attended the uveitis clinic. Additionally, the study included participants with all types of uveitis. We acknowledge that, as with all survey-based studies, there is an element of recall bias.The work carried out in this study and by NASS recognises the need to reduce the time to diagnosis of axSpA and seeks to improve the quality of life of patients with axSpA. IBP is not identified and is therefore underdiagnosed in patients with uveitis despite persistent back pain being prevalent in these patients. The lack of awareness of IBP leads to a delay in referrals to secondary care rheumatology services and increases the time to diagnosis and treatment. Improving education amongst primary care clinicians and ophthalmologists will increase the awareness of axSpA and aid identification and onward referral of patients with potential axSpA and ultimately reduce the delay in diagnosis. Moreover, a collaboration between ophthalmologists and rheumatologists will allow for the development of better internal referral pathways, increasing the number of referrals for a specialist rheumatological opinion and the potential diagnoses of axSpA.


Individuals with low back pain (LBP) may be classified based on mechanistic descriptors, such as a nociplastic pain presentation (NPP). The purpose of this secondary analysis was to examine the frequency and characteristics of patients with a NPP referred to physical therapy with LBP. Additionally, we characterized patients with LBP meeting the criteria for NPP by demographic, clinical, psychological, and pain sensitivity variables. Finally, we examined short- and long-term clinical outcomes in patients with a NPP compared to those without a NPP.  Patients referred to physical therapy for LBP completed the Patient Self-report Survey for the Assessment of Fibromyalgia. Participants were categorized as “LBP with NPP” or “LBP without NPP” based on the threshold established in this measure. A rank sum test examined for differences in pain-related psychological factors and pressure-pain threshold between groups. Next, a Friedman test examined if LBP intensity and disability trajectories differed by groups at one and six months after initiation of physical therapy. p < 0.05). Pressure-pain threshold did not differ between groups (p > 0.05). Individuals with LBP with a NPP demonstrated nonsignificant, small to medium reductions in pain and disability at one and six months. Individuals experiencing LBP without a NPP demonstrated significant reductions in pain and disability in the short- and long term.  22.2% of patients referred to physical therapy for LBP met the criteria for a NPP. Patients with a NPP reported significantly greater disability, pain catastrophizing, depression, anxiety, and somatization compared to individuals without a NPP ( Patients with LBP with a NPP displayed greater negative pain-related psychological factors but similar pain sensitivity compared to LBP without NPP. Low back pain (LBP) is the most common reason why patients seek rehabilitation in the world . While rOne method of subgrouping patients with pain is based on mechanistic descriptors . Pain isFibromyalgia is a chronic pain condition of unknown etiology characterized by widespread pain with fatigue and sleep disturbances –28. WhilTherefore, the first purpose of this secondary analysis is to determine the percentage of a sample of patients referred to physical therapy with LBP who meet the criteria for fibromyalgia, and therefore a NPP, based on the Patient Self-Report Survey for the Assessment of Fibromyalgia. The second purpose is to characterize patients with LBP meeting the criteria for fibromyalgia by demographic, clinical, psychological, and pain sensitivity variables. The third purpose is to determine if short- and long-term pain and disability outcomes differ between individuals with LBP with and without a NPP. This secondary analysis is clinically relevant as it applies a measure of NPP, identifies biopsychosocial differences between patients experiencing LBP with and without a NPP, and examines clinical outcomes.This is a secondary analysis of an observational, prospective cohort study conducted between December 2020 and August 2021. Data were collected from the following outpatient physical therapy clinics: six clinics within Brooks Rehabilitation in Jacksonville, Florida, USA, two clinics within the University of Florida Health in Gainesville, Florida, and one clinic within the University of Florida Health in Jacksonville, Florida. Thirteen physical therapists underwent IRB-01 training and a thirty-minute training session by the study coordinator to standardize data collection and recruitment methods. The University of Florida Institutional Review Board for Human Subjects Research approved this study and all participants provided written informed consent to enroll in the study.Participants who were between 18 and 75 years old and receiving outpatient physical therapy for LBP were eligible to participate in the study. LBP was defined as pain between the inferior posterior margin of the ribs and the horizontal gluteal fold . ParticiParticipants referred to physical therapy for LBP underwent a standard evaluation at the discretion of the physical therapist. During the initial evaluation or first follow-up appointment, the patient's physical therapist informed potential participants of the research using an IRB-approved script and study flyer. Interested participants were screened for eligibility criteria by study staff. Eligible participants who consented to participate completed self-report demographic and clinical measures, the Patient Self-Report Survey for the Assessment of Fibromyalgia, psychological measures, and clinical outcomes upon enrollment. Clinical outcomes of LBP intensity and disability were collected at baseline, one month, and six months after study enrollment allowing for short- and long-term assessments. Study enrollment was within two weeks of the physical therapy evaluation. In addition to self-report measures, physical therapists measured pressure-pain threshold (PPT) at the low back and upper trapezius allowing for assessment of local and remote pain sensitivity. Self-report questionnaires were collected and managed using Research Electronic Data Capture (REDCap) tools hosted at the University of Florida. REDCap is a secure, online software designed for collecting data in research studies. Participants underwent physical therapy treatment at the discretion of the physical therapist for the duration of the study and interventions were not standardized.Participants completed a self-report demographic form with age, sex, ethnicity, and race. The following clinical features of LBP were collected: duration of LBP in weeks, number of previous episodes, LBP intensity, and LBP-related disability.Participants rated their current, worst, and best LBP within the past twenty-four hours. These pain ratings were averaged, and the average LBP rating was reported and used in all analyses. LBP intensity was rated using a 101-point numerical pain rating scale (NPRS) where 0 = no pain and 100 = worst pain imaginable. A higher average pain rating indicates a higher LBP intensity. The NPRS demonstrates excellent psychometric properties –36. The LBP-related disability was measured with the Oswestry Disability Index (ODI), a reliable and valid measure of disability in patients with LBP . A higheThe Patient Self-Report Survey for the Assessment of Fibromyalgia is a five-item self-report questionnaire that measures the severity of fibromyalgia symptoms , 28. Park = 0.67), providing support for this assessment's validity [Prior research has reported a score of thirteen or higher on this measure indicates fibromyalgia . The Patvalidity .The Patient Self-Report Survey for the Assessment of Fibromyalgia is a screening tool intended for determining the prevalence of fibromyalgia in research. However, the questionnaire has been applied as a surrogate method to screen for subgroups of individuals with a nociplastic pain presentation in other populations, including myofascial pain .The SCL-90R is a ninety-item questionnaire that provides an overview of psychological symptoms in nine dimensions, including somatization, anxiety, and depression , 42. OnlThe PCS is a thirteen-item questionnaire in which higher scores indicate higher pain catastrophizing. This measure may be applied to individuals with painful conditions and demonstrates good internal consistency, reliability, and validity –46. PartThe FABQ includes a work and physical activity subscale with a higher score indicating greater fear-avoidance belief. The FABQ is a common measure in studies of individuals with LBP and is both reliable and valid –49. PartThe TSK is a self-report measure of fear of movement that demonstrates acceptable psychometric properties . Higher The PSEQ measures pain-related self-efficacy beliefs with higher scores indicating elevated levels of pain-related self-efficacy . ParticiThe PSQI is a self-report measure assessing sleep quality and disturbances in the past month . A cut-oPhysical therapists were trained by the study coordinator on the site of the PPT application, using the algometer, and applying pressure at a constant rate. A digital pressure algometer  with a 1 cm diameter rubber tip was applied at 1 kgf/s ipsilateral to the same side of the patient's LBP medial to the posterior superior iliac spine and upper trapezius. The algometer was applied to a site local to the participant's LBP and remote as a behavioral measure of local and widespread changes in pain sensitivity. Widespread reductions in pain threshold are observed in individuals with fibromyalgia compared to healthy controls, suggesting an overall lessening of pain sensitivity . ParticiSPSS v. 27  was used for all data analysis. Individuals who scored a thirteen or higher on the Patient Self-report Survey for the Assessment of Fibromyalgia met the criteria for fibromyalgia and, therefore, were categorized as LBP with NPP. Individuals who scored less than thirteen did not meet the criteria for fibromyalgia and were, therefore, categorized as LBP without NPP. Therefore, two groups were formed (1) LBP with NPP and (2) LBP without NPP. Characteristics of the total sample, as well as each group, were determined using descriptive statistics and frequency analysis for continuous and categorical variables, respectively.The first purpose of this secondary analysis was to determine the percentage of a sample of patients referred to physical therapy with LBP who met the criteria for fibromyalgia, and therefore a NPP, based on the Patient Self-Report Survey for the Assessment of Fibromyalgia. A frequency analysis was conducted to determine the percentage of patients within each group.n < 20), nonparametric tests were used for data analysis. Group differences in demographic, clinical, and psychological characteristics were determined with a rank sum test for continuous variables and Chi-Square Analysis for categorical variables. An alpha level of 0.05 was established. The following demographic factors were examined: age, sex, race, and ethnicity. The following clinical factors were examined: average LBP rating on the NPRS, total percentage on the ODI, pain duration, and the number of previous episodes of LBP. The following psychological and sleep characteristics were examined: (a) somatization, depression, and anxiety collected as part of the SCL-90R; (b) pain catastrophizing collected with PCS; (c) fear-avoidance beliefs collected with FABQ-PA, FABQ-W; (d) kinesiophobia collected with TSK; (e) self-efficacy collected with PSEQ; and (f) sleep quality with PSQI. To examine differences between groups by local and remote changes in pain sensitivity, a separate rank sum test with PPT applied to the low back or upper trapezius as the dependent variable and group (LBP with NPP or LBP without NPP) as the independent variable was conducted. Due to the difference in the number of participants in each group and less than twenty participants in one group, hedge's g was calculated as a measure of effect size with the following formula: (x1 − x2)/√ ((n1 − 1) × s12 + (n2 − 1) × s22)/(n1 + n2 − 2)). Effect sizes were interpreted as follows: 0.2 = small, 0.5 = medium, 0.8 = large. [The second purpose was to characterize patients with LBP meeting the criteria for fibromyalgia by demographic, clinical, psychological, and pain sensitivity variables. Due to the small sample of individuals with NPP . 41 participants completed all follow-up measures at six months (76% follow-up rate). During the four weeks, participants underwent physical therapy at the clinician's discretion. Physical therapy treatment was not standardized.n = 12) of patients with LBP met the threshold for a diagnosis of fibromyalgia, and therefore a NPP, based on the Patient Self-Report Survey for the Assessment of Fibromyalgia at baseline.22.2% (p > 0.05).As demonstrated in p=0.18) and previous number of episodes (p=0.18) did not differ by group. As shown in p=0.19). Patients with LBP and NPP reported significantly higher disability (p=0.01) [Average LBP intensity and disability at baseline were moderate for the total sample (mean ± SD pain = 50.28 ± 22.00 and disability = 36.82 ± 18.60%). Average back pain duration and a number of previous episodes indicated the total sample was predominantly individuals with chronic LBP.  Pain dur(p=0.01) . Collectp < 0.01, g = 1.18), depression , and anxiety  were significantly higher in patients with LBP with NPP compared to LBP without NPP. Pain catastrophizing was also significantly higher in patients with LPB with NPP compared to LBP without NPP . Measures of fear-avoidance beliefs were not significantly different between groups . Individuals with LBP with NPP also displayed significantly lower levels of pain-related self-efficacy . Sleep quality, while worse in people with NPP, did not significantly differ between groups  yet a medium to large effect size was observed. People with NPP had worse sleep quality than those without NPP although the difference did not quite reach the 5% threshold needed to reject the null hypothesis (p = 0.06).All negative pain-related psychological factors significantly differed between groups, with the exception of fear-avoidance beliefs. As demonstrated in p=0.89, g = 0.03; upper trapezius p=0.67, g = 0.21). Pain ratings at threshold also did not differ between groups .As demonstrated in p=0.09) for patients with LBP with NPP between baseline to one month (g = 0.29) and six months (g = 0.36). Although not significant, effect sizes suggest small to medium reductions in pain in the short- and long-term pain for patients with LBP with NPP. For patients with LBP without NPP, pain significantly reduced (p < 0.01) between baseline to one month (g = 0.51) and six months (g = 0.51). Medium effect sizes for changes in pain were observed for patients with LBP without NPP. Effect sizes for differences in pain ratings between those with and without a NPP were small at baseline (g = 0.26), one month (g = 0.44), and six months (g = 0.27).As demonstrated in p=0.09) between baseline to one month (g = 0.27) and six months (g = 0.51). Although not significant, a small reduction was observed at one month and a medium reduction in disability was observed at six months. Disability significantly (p=0.02) reduced over time for patients displaying LBP without NPP between baseline to one month (g = 0.25) and six months (g = 0.51). Effect sizes for differences in disability between those with and without a NPP ranged from large to medium at baseline (g = 0.96), one month (g = 0.54), and six months (g = 0.40).As demonstrated in Clinical features, such as pain duration, are part of the criteria for determining nociplastic pain in patients with musculoskeletal pain . FurtherApproximately one quarter (22%) of our sample of patients with LBP met the threshold for a NPP based on the Patient Self-Report Survey for the Assessment of Fibromyalgia at baseline. Other investigators have reported higher frequencies of a NPP in patients with chronic LBP. A prior study reported 48% of patients with chronic LBP were identified as fibromyalgia positive based on the 2011 Fibromyalgia survey (Widespread Pain Index and Symptom Severity) . In thisThe results of this study suggest that pain-related psychological factors may be a key differentiating characteristic in patients with and without a NPP. Higher pain catastrophizing, depression, anxiety, and somatization, as well as lower pain self-efficacy, were reported in patients with LBP with NPP compared to those without a NPP. Multiple pain-related psychological factors may impact the pain experience for individuals with NPP. Consistent with prior literature, catastrophizing is associated with higher pain perception in patients with fibromyalgia  and is pIn our sample, a clinically feasible measure of pain sensitivity (pressure-pain threshold) did not differentiate patients with LBP with NPP from patients without a NPP. This result is inconsistent with prior literature demonstrating patients with fibromyalgia display elevated thermal and pressure sensitivity compared to healthy controls , 67. PatA NPP has important clinical implications as it also impacts short- and long-term reductions in pain and disability after physical therapy. Our results indicate individuals with LBP without NPP demonstrate significant reductions in pain and disability at one and six months with small to medium effect sizes. However, individuals with LBP with a NPP demonstrate small to medium but nonsignificant reductions in pain and disability at one and six months. This questionnaire has been previously applied as a surrogate measure of NPP to examine the prevalence of this presentation in musculoskeletal pain conditions, such as LBP , 74. ConThere are strengths and limitations worth considering when interpreting the results of this analysis. A strength of our study is we administered a multidimensional assessment of pain including multiple psychological questionnaires, pain sensitivity, and clinical outcomes. Additionally, our results are clinically relevant with the inclusion of short- and long-term outcomes. However, a limitation of our study is that the Patient Self-Report Survey for the Assessment of Fibromyalgia has not been previously examined for validity or reliability in individuals with LBP. Treatment was also provided at the discretion of the physical therapist which could influence clinical outcomes. Additionally, as a secondary analysis, we did not specifically enroll patients who met the criteria for a NPP. As a result, we had an unequal number of participants in each group with a small sample size of individuals with a NPP.In conclusion, approximately one-quarter of patients referred to physical therapy for LBP were identified as having a presentation consistent with LBP and NPP. Patients with LBP plus NPP were further characterized by greater disability, negative pain-related psychological factors, and decreased short- and long-term reductions in pain intensity and disability. Pain catastrophizing, depression, anxiety, and somatization are psychological factors rehabilitation providers may choose to screen and monitor in individuals with a NPP. Individuals with LBP with a NPP also demonstrate nonsignificant decreases in pain and disability at one month and six months after rehabilitation compared to individuals without a NPP. These results are clinically meaningful as pain-related psychological factors may represent novel therapeutic targets.


To compare the clinical and radiographic outcomes of oblique lateral lumbar interbody fusion and minimally invasive transforaminal lumbar interbody fusion in patients with grade‐1 L4/5 degenerative spondylolisthesis.n = 36) or minimally invasive transforaminal LIF  at the Department of Spine Surgery, Beijing Jishuitan Hospital from January 2016 to August 2017. Patient satisfaction Japanese Orthopaedic Association score, visual analog scale (VAS) scores for back and leg pain, Oswestry disability index (ODI), radiographic outcomes including anterior/posterior disc heights (ADH/PDH), foraminal height (FH), foraminal width (FW), cage subsidence, cage retropulsion, and fusion rate were assessed during a 2‐year follow‐up. Continuous data are presented as mean ± standard deviation and were compared between groups using the independent sample t‐test. Categorical data are presented as n (%) and were compared between groups using the Pearson chi‐squared test or Fisher's exact test. Repetitive measurement and analysis of variance was employed in the analysis of ODI, back pain VAS score, and leg pain VAS score. Statistical significance was defined as p < 0.05.Based on the inclusion and exclusion criteria, the comparative analysis included consecutive patients with grade‐1 degenerative spondylolisthesis who underwent oblique LIF , lower back pain VAS score (2.42 ± 0.81 vs 3.38 ± 0.47), and ODI score (20.47 ± 2.53 vs 27.31 ± 3.71) at 3 months follow‐up , but higher leg pain VAS scores at all postoperative time points than the MI‐TLIF group . ADH, PDH, FD, and FW improved in both groups post‐surgery. At the 2 year follow‐up, the OLIF group had a higher rate of Bridwell grade‐I fusion  and lower incidences of cage subsidence  and retropulsion  than the MI‐TLIF group.The OLIF and MI‐TLIF groups comprised 36 patients  and 45 patients , respectively. Satisfaction rates at 2 years post procedure exceeded 90% in both groups. The OLIF group had less intraoperative blood loss (140 ± 36 In patients with grade‐I spondylolisthesis, OLIF was associated with lower blood loss and greater improvements in VAS for back pain and ODI and radiologic outcomes than MI‐TLIF. The OLIF is more suitable for these patients with low back pain as the main symptoms are accompanied by mild or no leg symptoms before operation. Milder back pain symptoms in the OLIF group at 3 months may have been due to less iatrogenic violation of the posterior lumbar elements than that which occurs after MI‐TLIF. Symptoms of degenerative spondylolisthesis include back pain, leg pain, and neurogenic claudicationet al. in 2003Emerging minimally invasive techniques, such as minimally invasive TLIF (MI‐TLIF) and oblique lumbar interbody fusion (OLIF), are progressively changing the treatment modalities for patients suffering from degenerative lumbar diseases. MI‐TLIF achieves direct decompression of spinal neural elements and was first described (using a tubular retractor) by Foley MI‐TLIF is a technically challenging operation often performed in a limited working space. A previous study utilizing MI‐TLIF reported that the total complication rate was 8.11%et al. investigated the oblique lateral corridor between the peritoneum and psoas muscle without dissecting or traversing the psoas muscle, and concluded that the corridor provides safe and easy access to the L2–S1 intervertebral discs with minimal psoas retractionOLIF utilizes the ante‐psoas muscle approach to exert an alternative mechanism of action, providing indirect neural decompression by expansion of the bony neuroforamen and distraction of the ligamentous stenosis of the central canal. In experiments on cadavers, Davis In this study, we performed a retrospective analysis to compare the clinical and radiographic outcomes of oblique lateral lumbar interbody fusion and minimally invasive transforaminal lumbar interbody fusion in patients with grade‐1 degenerative spondylolisthesis (L4/5). Our research questions included the following. First, are OLIF procedures performed on patients with grade‐1 degenerative spondylolisthesis (L4/5) feasible and safe? Second, does minimally invasive transforaminal lumbar interbody fusion result in a stable internal fixation, reduced surgical trauma, and early postoperative recovery? Third, what perioperative complications are associated with the two surgical techniques?This study was a retrospective analysis of patients with spondylolisthesis who underwent one of the two surgical procedures at our hospital between January 2016 and August 2017. The inclusion criteria were: (i) spondylolisthesis of Meyerding grade 1 (slippage ≤25%) at the L4–L5 level was confirmed by radiography , and informed consent was waived due to the retrospective design of the study.OLIF and MI‐TLIF were performed under general anesthesia. The same chief surgeon, who had 24 years of experience in spinal surgery, performed all the operations. All patients were discharged 7 days after surgery.via blunt dissection, and the peritoneum was mobilized anteriorly to expose the anatomical oblique lateral corridor. An intervertebral cage  filled with demineralized bone matrix  was inserted.OLIF was performed using a standard procedureSubsequently, the patient was placed in the prone position to undergo posterior bilateral percutaneous pedicle screw fixation . None of the patients in the OLIF group underwent additional laminectomy for the level of spondylolisthesis observed.MI‐TLIF was carried out using a standard methodPosterior bilateral percutaneous pedicle screw fixation  was performed in all patients.The following demographic and operative data were extracted from the medical records: sex, age, weight, BMI, and intraoperative blood loss.The following assessments were made before surgery and postoperatively at 1 week, 3 months, and 2 years, respectively: visual analog scale (VAS) scores for back pain and leg pain; Oswestry Disability Index Patient satisfaction with treatment was determined using the Japanese Orthopaedic Association (JOA) scoring systemThe JOA score is composed of four sections: subjective symptoms , clinical signs , restriction of activities of daily living (seven items), and urinary bladder function as minus points.Oswestry Disability Index (ODI) is a principal, condition‐specific outcome measure used in the management of spinal disorders, and to assess patient progress in routine clinical practice. A value of 0%–20% is considered mild dysfunction, 21%–40% is moderate dysfunction, 41%–60% is severe dysfunction, and 61%–80% is considered as disability. For cases with score of 81%–100%, they are considered as either long‐term bedridden, or exaggerating the impact of pain on their life.The visual analog scale (VAS) of the lower limbs and back were analyzed to evaluate the effects of treatment on lower limb symptoms. Using a VAS ruler, A higher score indicated greater pain intensity. Patients described their lower leg pain intensity as 0 (no pain) to 10 (worst pain ever).Evaluation of cage position was based on the imaging investigations. Cage subsidence was defined as being present if a cage was observed to sink into an adjacent vertebral body by >2 mm, based on comparisons with previous CT imagesRadiologic measurements Figure  includedn (%) and were compared between groups using the Pearson chi‐squared test or Fisher's exact test. Repetitive measurement and analysis of variance was employed in the analysis of ODI, back pain VAS score, and leg pain VAS score. Statistical significance was defined as p < 0.05.Statistical analyses were performed using SPSS 18.0 . Continuous data are presented as mean ± standard deviation and were compared between groups using the independent sample t‐test. Categorical data are presented as vs 233 ± 62 ml, p < 0.001).A total of 81 patients were included in the analysis, and demographic profile and operative characteristics of patients are presented in Table vs MI‐TLIF group 23 ± 2.2 months), 76/81 of patients (93.8%) returned to our hospital for their follow‐up visit. Follow‐up was conducted by telephone for the five patients who lived too far from our hospital to return at 24 months, and their 24‐month CT and MRI scans  were sent to our hospital for analysis. Thus, follow‐up data were available for all 81 patients.At 24 months . Milder back pain symptoms in the OLIF group at 3 months may have been due to less iatrogenic violation of the posterior lumbar elements than that which occurs after MI‐TLIF  and 3 months , with a trend toward a lower value at 2 years postoperatively  despite being significantly lower preoperatively  and at 1 week (p < 0.001) and 3 months (p = 0.003) postoperatively (Table PDH was significantly higher in the MI‐TLIF group than in the OLIF group preoperatively (p = 0.002) and at 1 week (p = 0.003), 3 months (p = 0.002), and 2 years (p = 0.004) postoperatively  or posterior disc height (mm), but foraminal height. There was no significant difference in the FH baseline (preoperative) between two groups.FH and FW showed improvements after surgery in both groups Table . FH did  p = 0.00, 3 monthvs 62.2%, p = 0.042) and at 24 months .The rate of complete fusion (grade I according to Bridwell's criteria) was significantly higher in the OLIF group than in the MI‐TLIF group at 3 months  and at 24 months postoperatively  suffered intraoperative dural tears during nerve decompression and developed cerebrospinal fluid leak. Three patients in the MI‐TLIF group complained of leg pain/numbness at 24 months after surgery. These three patients had cage retropulsion and a fusion grade of IV, and their pain resolved after revision surgery to reinsert the cage and compress the adjacent vertebrae. Two patients in the MI‐TLIF group suffered right L5 root palsy due to a local hematoma but recovered within 3 months.The present study compared the effects of oblique lateral lumbar interbody fusion and minimally invasive transforaminal lumbar interbody fusion in patients with grade‐1 degenerative spondylolisthesis (L4/5).The findings showed that back pain VAS score at 3 months was significantly lower in the OLIF group than in the MI‐TLIF group. Milder back pain symptoms in the OLIF group at 3 months may have been due to less iatrogenic violation of the posterior lumbar elements than that which occurs after MI‐TLIF. An additional advantage of OLIF over MI‐TLIF is that the cage can achieve greater sagittal angle improvement by being implanted in the front third of the disc, which helps relieve tension in the paravertebral muscles. It was also notable that the ODI score at 3 months was significantly lower in the OLIF group than in the MI‐TLIF group, suggesting that OLIF may have advantages over MI‐TLIF with regard to achieving the intended surgical outcomes.2) than in the MI‐TLIF group . The wider footprint of the cage used for OLIF may provide a more effective biological environment for the fusion process, reducing the chances of cage subsidence. Consistent with this proposal, Tohmeh et al. found that severe subsidence (≥4 mm) was more likely for a 50‐mm cage than for a 60‐mm cageet al. reported a significantly higher rate of endplate damage with the transforaminal approach (48%) than with the lateral approach (4%)et al. identified 13 patients (14 operative segments) with cage subsidence, with all cases occurring in the inferior endplatesThe incidence of cage subsidence as a complication of lateral lumbar interbody fusion (LLIF) was 10.84% in this studyet al. proposed that proper annular tension may reduce the risk of implant migrationCage retropulsion may result in the loss of lumbar lordosis, a narrowing of the disc space and foramina, direct compression of the nerve roots and a lower fusion rateet al. showed that the symptoms of sympathetic nerve injury can last up to 53 monthset al. reported that complications of OLIF occurred in three of 21 patients The most common complications of OLIF are lumbar sympathetic trunk injury and segmental artery injury, and neurogenic pain is commonly aggravated at nightThis study had several limitations. First, this was a retrospective study, so the analysis may have been affected by information bias or selection bias. Second, this was a single‐center study with a small sample size. Third, the follow‐up time was limited to 2 years, so longer‐term outcomes were not evaluated. Fourth, some of the indicators should be undertaken on subgroup analysis based on age, gender, classification in the future research.In patients with grade‐I spondylolisthesis, OLIF was associated with less blood loss and better improvements in some clinical (VAS for back pain and ODI) and radiologic outcomes than MI‐TLIF, although patients in the OLIF group had higher leg pain VAS scores than patients in the MI‐TLIF group. As the greatest limitation of OLIF is indirect decompression, the ability to relieve symptoms of lower limbs is limited. Our advice is to choose patients with low back pain as the main symptoms, accompanied by mild or no leg symptoms before operation. Moreover, during OLIF surgery, particular attention should be paid to the lumbar sympathetic trunk to reduce postoperative neurologic complications.All authors declare that they have no competing interests.This study was funded by Capital's Funds for Health Improvement and Research (2020–2‐2072), Beijing Natural Science Foundation (L202005), Beijing Jishuitan Hospital “Medical and Engineering Intersection Project” (#YGQ‐201907), Beijing Jishuitan Hospital “Nova Program” (#XKXX201808), and Beijing Hospital Authority Youth Program (#QML20190403).Da He and Wei He carried out the studies and drafted the manuscript. Bo Liu, Yajun Liu, Yuqing Sun, and Yonggang Xing performed the statistical analysis and participated in its design. Zhao Lang, Yumei Wang, Tengfei Ma, and Mingming Liu collected data. Wei Tian participated in acquisition, analysis, or interpretation of data and drafted the manuscript. All authors read and approved the final manuscript.


STM was applied twice a week for four weeks, with a total of eight sessions, and PNE was applied within four weeks, for a total of two sessions. The primary outcome was pain intensity, and the secondary outcomes were central sensitization, pressure pain, pain cognition, and disability. Measurements were made at baseline, after the test, and at 2-week and 4-week follow-ups. The BG showed significant improvement in pain intensity (p < 0.001), pressure pain (p < 0.001), disability (p < 0.001), and pain cognition (p < 0.001) compared to the SMG. This study demonstrated that STM plus PNE is more effective for all measured outcomes compared to STM alone. This finding suggests that the combination of PNE and manual therapy has a positive effect on pain, disability index, and psychological factors in the short term.This study was conducted to demonstrate the therapeutic effect of soft-tissue mobilization (STM) combined with pain neuroscience education (PNE) for patients with chronic nonspecific low back pain with central sensitization. A total of 28 participants were recruited and randomly allocated to either the STM group (SMG) ( Chronic nonspecific low back pain (CNLBP) accounts for 85–90% of chronic low back pain, and the underlying pathological mechanism remains unclear ,2. AccorA biopsychosocial approach is recommended to understand and manage central sensitization . Based oIn a meta-analysis of the effects of PNE on kinesiophobia in patients with chronic pain, it was reported that a combined intervention of manual therapy and exercise therapy was effective in improving chronic pain and kinesiophobia ,6,11. SiPrevious studies have confirmed that PNE and STM can improve pain, disability, and psychological factors related to CNSLBP or central sensitization ,13,14. TThis study was a prospective, parallel-arm, assessor-blinded, randomized, active-controlled trial. The trial protocol was conducted from August to October 2021 after pre-registration (No. KCT0006455).This study included patients who visited the Gwangju Heemang Hospital  in August 2021 with a primary complaint of low back pain (LBP). Patients were diagnosed with low back pain based on radiological examination, physician screening, and history taking. Among them, patients with CNLBP of an unknown cause were recruited through an in-hospital bulletin board announcement, excluding specific pathologies  of known cause.The inclusion criteria were: male and female patients between the ages of 20 and 75 years who were diagnosed with CNLBP and had symptoms of >12 weeks; scored ≥28 points on the Korean version of the central sensitization inventory (CSI-K); and had an LBP of 3 or higher on the numeric pain rating scale (NPRS) within the last 7 days .Exclusion criteria included the following: a history of neck or back surgery within the past 3 years; a diagnosis of mental illness; patients with rheumatic disease, neurological disease, heart disease, respiratory disease, metabolic disease, endocrine disease, fibromyalgia, or chronic fatigue syndrome; patients with the same chronic pain syndrome; loss of skin sensation; skin inflammation or swelling on the back; and the use of painkillers or oral and systemic steroids for more than 10 days a month ,18,19,20Before the trial started, participants were provided with information about the study and possible risk factors. Afterwards, the participants were asked to sign a consent form and were informed that they could withdraw their participation at any time. This study was approved by the Institutional Review Board of Sahmyook University (No. 2-1040781-A-N-012021090HR).To calculate the sample size, the effect size f(V) for pain intensity was set at 0.25 based on a previous study  in whichThe study participants were randomly allocated to two groups, i.e., soft-tissue mobilization group (SMG) and blended group  using a random allocation software , with a four-digit number identification code. The investigators and participants were not blinded, and only the assessors were blinded to all measurements.All participants underwent STM two sessions per week for 40 min per session for four weeks. Additionally, the BG received two sessions (30–50 min) before and after receiving STM. All participants were controlled for factors influencing outcomes such as medical treatment, exercise, and supplements while the intervention was provided.Four STM techniques were used for STM, including transverse sliding of the lumbar muscles, thoracolumbar myofascial release, quadratus lumborum myofascial release, and psoas myofascial release ,21.Transverse sliding of the lumbar muscles was performed in prone position. The physical therapist performed transverse sliding along the paraspinal muscles using the elbow, three times on each side.Thoracolumbar myofascial release was performed in the prone position. The physical therapist crossed and contacted the participant’s T12-L1 level and sacrum using their hands. After contact, care was taken not to slide over the skin or apply strong pressure to the tissue, which was carried out along the fascia for at least 5 min.Quadratus lumborum fascia release was performed in the prone position. The physical therapist’s elbow was brought into contact with the participant‘s quadratus lumborum muscle above the iliac crest, and the participant‘s thigh was gripped and fixed with the opposite hand. Subsequently, the physical therapist’s elbow applied low-intensity pressure toward the participant’s spine and the hand located on the thigh was gently pulled downward. The technique took 7 min on each side.The psoas fascia was released with the patient in the supine position. The physical therapist’s hand was brought into contact with the participant’s navel (3 cm on each side) and relaxation of the fascia was induced through horizontal sliding. This technique was performed 15 times on each side.The educational program was structured based on the pain neuroscience curriculum based on the revised Neurophysiology of Pain Questionnaire (rNPQ) included in “Pain Neuroscience Education” ,22 Tabl.The first session was held in the hospital’s rehabilitation treatment room before the STM program started. The training was conducted through examples, metaphors, and verbal explanations using Power Point™  to enhance understanding . After tThe second session was held at the same place after the end of STM . It was The total study period was eight weeks, consisting of a four-week intervention period and a four-week follow-up period. Before the intervention was provided, participants had a baseline measurement, and after the intervention was completed, they received a post-test, follow-up at two weeks, and follow-up at four-week assessment as well.The NPRS is a pain intensity rating scale consisting of an 11-point scale ranging from 0 (no pain) to 10 (worst pain). In this study, triple NPRS was applied as an evaluation method of NPRS, which calculates the overall average by receiving the patient’s highest and lowest pain scores for the current and previous 24 h . The intr = 0.817, the internal agreement was reported as Cronbach’s α = 0.879 [The CSI is a comprehensive screening tool developed to evaluate central sensitization symptoms in patients with chronic pain and is an effective treatment outcome measurement tool . CSI con = 0.879 , and the = 0.879  for CLBP = 0.879 .2. Based on the study by Paulo et al. [2 (1 kgf/cm2) per second vertically to the skin on average until the participant complained of pain or discomfort [Pressure pain threshold (PPT) was measured using a digital algometer  with a probe surface area of 1 cmo et al. , who appo et al. . The evascomfort . If theyscomfort , who stuscomfort , and MCIscomfort .The pain catastrophizing scale (PCS) is a common assessment tool used to measure pain catastrophizing  and evalr = 0.29 to 0.69 [The Tampa scale of kinesiophobia-17 (TSK-17) is a self-report questionnaire frequently used to assess fear of movement . There a to 0.69 , and the to 0.69 .The Korean version of the Roland Morris Disability Questionnaire (K-RMDQ) is designed for self-reporting disability due to LBP . It const-test. Mauchly’s test was performed for all variables measured according to the time point and the assumption of sphericity was satisfied.SPSS  was used for data analysis. The mean and standard deviation of all collected data were calculated using descriptive statistics, and normal distribution was verified using the Shapiro–Wilk test. The general characteristics of the participants were verified for homogeneity using the chi-squared test and independent samples t-test was conducted as a post hoc test for differences between groups at each time point. The main effect of time was determined by performing one-way RM ANOVA. If a main effect of time was demonstrated, post hoc tests were conducted for differences at each time point relative to the baseline. The statistical significance level (α) for analysis of variance was set at 0.05. The significance level for the post hoc test was corrected using Bonferroni’s method, with the significance level (α) of the group comparison by time point being 0.013 and the significance level (α) of the post hoc test for the comparison between the time points being 0.017. In the ANOVA results, partial eta square  was performed to examine the interaction between time and group. When the interaction was proven, an independent sample This study is a Consolidated Standards of Reporting Trials (CONSORT)-compliant randomized controlled trial. F = 14.951, p < 0.001, p < 0.013) (The NPRS showed an interaction between time and group (< 0.013) .The comparison of effect sizes between groups by measurement time point, post-intervention, and 2- and 4-week carryover effects all showed a larger effect size in the BG compared to the SMG  Table 4Table 4.F = 33.829, p < 0.001, p > 0.013) (The CSI-K showed an interaction between time and group (> 0.013) . Neverth> 0.013)   (The PPT showed an interaction between time and group (< 0.013) . Similar< 0.013)   (The K-PCS showed an interaction between time and group (< 0.013) . Similar< 0.013)    . Similar< 0.013)   (The K-RMDQ showed an interaction between time and group (< 0.013) . In the comparison of effect sizes between groups by measurement time points—post-intervention, 2-week carryover, and 4-week carryover effects—all showed a larger effect size in the BG than in the SMG  Table 4Table 4.p < 0.001). In the post hoc tests, a significant difference was found in all variables except CSI-K at follow-up (2-week and 4-week) (p < 0.013). BG had a larger effect size than SMG in the comparison of effect sizes between the groups.This study is the first to combine STM and PNE for treating patients with CNLBP with central sensitization. By comparing the effects of STM alone and STM plus PNE, this study aimed to determine their effects on pain intensity, central sensitization, pressure pain, pain cognition, and disability. The results showed a significant interaction between time and group for all variables (In the NPRS, a primary outcome measure, only the BG showed a decrease of two or more points in the MCID. These results suggest that the addition of PNE is more effective in helping control pain intensity. This may be due to the fewer fear-avoidance beliefs observed in patients with high pain knowledge. Notably, fear-avoidance beliefs are positively correlated with pain intensity ,45. In aIn the secondary outcome measures, CSI-K showed a significant interaction between time and group but no significant time point was found in the post hoc test. However, when compared to the reported MDC, there was a significant difference between the two groups. Considering the difficulty in suggesting a clear mechanism, and the fact that Nijs et al.  focused In pain cognition, both the K-PCS and TSK-17 showed an interaction between time and group. In the post hoc test of the post-test and follow-up after 2 and 4 weeks, the BG showed a positive improvement compared to the SMG. As if indicating the effect of additional PNE, there was a meaningful change only in the BG in the reported MCID. It has been reported that reconceptualization through an increase in knowledge about pain through PNE shows a positive improvement in catastrophizing pain, which could lead to improvement in kinesiophobia by gradually lowering fear and inducing movement ,49,50. SThese results demonstrate the positive effect of PNE plus STM, compared to the effect of PNE alone. PNE has been reported to last for 3 months due to long-term retention of pain knowledge, even if only given once . These rIn addition, according to the effect size results of this present study, the effect of STM showed more than a moderate effect in all variables except for PCS-K. As a basis for interpreting the results of this study, it has been reported that STM, which is included in massage therapy, induces a decrease in cortisol and an increase in serotonin, dopamine, and oxytocin in response to stressful experiences ,52,53. SThese findings may provide options for physical therapists to consider cognitive factors of pain as well as biological interventions when managing patients with central sensitization. In further studies, physical therapists should consider applying 1:1 sessions and longer follow-ups to provide maximum benefit to individual patients . LikewisIn conclusion, STM plus PNE may be provided as a sufficient treatment option for positive improvement in pain, pain cognition, and disability in patients with CNLBP with central sensitization when compared to STM alone.


Musculoskeletal spine disorders, especially low back pain, induce enormous amounts of stress and financial burden on individuals and healthcare systems throughout the world. Disorders of the facet joints in the lumbar spine are the most predominant cause of back pain, resulting in facet joint syndrome (FJS). Conventional treatments for FJS are short-lived and have limitations and side effects. Thus, safer and more effective alternatives that can reduce pain and improve patient-reported outcomes are needed. Recently, the utilization of biologics, including the ones derived from perinatal tissue such as amniotic membrane (AM) and umbilical cord (UC), has significantly increased for regenerative medicine applications. This manuscript summarizes the outcomes of preclinical and clinical studies utilizing AM and/or UC for FJS. We identified no preclinical studies and 3 retrospective studies utilizing the search terms “amniotic membrane” and/or “umbilical cord” and “facet joint syndrome”. The administration of AM + UC is safe and potentially efficacious for patients with FJS. However, more preclinical studies and appropriately powered, multi-center, prospective non-randomized and randomized controlled studies with longer follow-up are warranted to further evaluate the efficacy of AM + UC to justify its clinical use. Musculoskeletal disorders are a leading cause of disability and significantly impact physical activity and sleep quality, inducing depression and cognitive impairment , 2. ChroCurrent conservative multimodal treatment for FJS consists of activity modification, physical therapy, non-steroidal anti-inflammatory drugs (NSAIDs), non-narcotic and narcotic analgesics, and steroids –13. ThesA search was performed using the terms “amniotic membrane” and/or “umbilical cord” and “facet joint syndrome” in PubMed, ScienceDirect and Google Scholar databases for articles published in English to May 28, 2023. All preclinical and clinical studies utilizing AM and/or UC for facet joints were included in this manuscript. Studies not using AM and/or UC or not focusing on management of FJS were excluded. A flow diagram is shown in Fig. In addition, we searched ClinicalTrials.gov using the same search terms to identify registered trials on the use of AM and/or UC for the management of FJS.To date, no preclinical studies regarding the use of amniotic membrane and/or umbilical cord tissue for the treatment of FJS have been published.p < 0.05) reduced to 0.4 ± 0.7 (94.6% reduction) at 6 months follow-up. Additionally, all patients at presentation reported pain despite oral NSAIDs and acetaminophen, and 4 patients took opioids  per day). At 6 months follow-up, all patients had stopped pain medications including opioids. Moreover, no additional interventions were needed, and no adverse events were reported during the 6 months of follow-up. Despite the small sample size, this was one of the first studies demonstrating safety and efficacy of AM + UC in patients suffering with FJS.A retrospective chart review assessed the safety and effectiveness of intra-articular AM + UC in providing symptomatic relief in patients with FJS . PatientN = 38) of the patients showed at least 30% improvement  and 57.4% (N = 31) of the patients showed at least 50% improvement  in PGIC. The mean PGIC improvement was 65.3%, 67.5%, 56.9%, 56.7% for responders30 and 72.2%, 69.6%, 65.0%, 45.0% for responders50 at 6 weeks and 3, 6 and 12 months follow-up visits, respectively. The number of patients using NSAIDs decreased significantly (p < 0.01) at follow-up visits compared to baseline, with no change for opioid users. Additionally, no adverse events were reported during 12 months of follow-up. Despite limitations such as small sample size and the retrospective nature of the study, the results are in accordance with study by Bennett et al. [A retrospective cohort study evaluated the safety and efficacy of AM + UC injection in managing FJS pain . Patientt et al.  and demon = 44), intervertebral disk disease in 59.6% (n = 31), and radiculopathy in 34.6% (n = 18) of the patients. The pain scores significantly (p < 0.05) reduced at 2 weeks (3.4 ± 2.3) and at 3–4 weeks (3.5 ±) compared to baseline pain score (4.9 ± 2.2). The pain score also reduced at 6 weeks and 8 weeks, but the change was not significant (p > 0.05) compared to baseline. However, at a mean follow-up time of 10.6 ± 5.4 weeks, pain was significantly reduced compared to baseline (p < 0.0001). All patients also reported improvements in pain, ROM and sensation. No severe adverse events were reported throughout the duration of this study. The results from this study are in accordance with aforementioned studies [A retrospective chart review evaluated the safety and efficacy of AM + UC in patients with spinal musculoskeletal disorders . Inclusi studies , 24 and As of 28 May 2023, there are no clinical trials registered on clinicaltrials.gov  evaluating the safety and efficacy of amniotic membrane and/or umbilical cord for the treatment of facet joint syndrome.The present study evaluated the therapeutic potential of AM and/or UC for the management of FJS. Preclinical and clinical studies focusing on the effect of AM and/or UC tissue and derived mesenchymal stem cells on FJS were included. Based on our search strategy and inclusion/exclusion criteria, no preclinical studies and only three clinical studies fit the scope of our study.The treatment of chronic back pain resulting from FJS poses a great challenge to physicians . The lacDespite constraints, including lack of preclinical and prospective clinical studies, the aforementioned retrospective studies show that administration of AM + UC is safe and potentially efficacious in patients with FJS. However, more in vitro and preclinical studies are warranted to determine the mechanism of action of AM and/or UC tissue and associated mesenchymal stem cells in managing FJS. Additionally, appropriately powered, multi-center, prospective non-randomized and randomized controlled studies with longer follow-up are required to further assess the efficacy of AM + UC and ultimately justify its clinical use in FJS patients.


In the treatment of knee osteoarthritis (KOA), there is a need for the long-term use of therapeutic drugs that reduce joint pain and have fewer adverse effects. This study aimed to investigate the therapeutic effect of bean pressing on ear points on early KOA pain. One hundred patients with KOA recruited at the Wenzhou Hospital of Traditional Chinese Medicine between February 2019 and May 2022 were divided randomly into a treatment group  and WOMAC scores of the treatment group were significantly lower than those of the control group ( Auricular bean-pressing therapy had an analgesic effect and could also alleviate mild to moderate KOA swelling, joint stiffness, and other symptoms, effectively reducing the demand for NSAIDs and improving both knee function and quality of life. The results suggested that auricular bean-pressing therapy has promising prospects in the treatment of early KOA pain. Its clinical manifestations include pain, swelling, and limited mobility, and in severe cases, it may lead to knee disability, which more frequently occurs in middle-aged and elderly people . The maiAuricular point bean pressing involves pressing and fixing cowherb seed on the auricular points to continuously stimulate them and create a therapeutic effect . The met2.2.1This was a randomized controlled trial. One hundred participants were selected from patients with KOA who were treated at the Department of Orthopedics of Wenzhou Hospital of Traditional Chinese Medicine between February 2019 and May 2022. The standard follow-up for all treated patients lasted 4 weeks. The study was approved by the ethics committee of the Wenzhou Hospital of Traditional Chinese Medicine Affiliated to Zhejiang University of Traditional Chinese Medicine , and all patients provided signed informed consent for their inclusion in the research. The study met the requirements of the Declaration of Helsinki.One hundred patients with KOA enrolled in this study were divided into control and study groups (The inclusion criteria were: (1) patients nce (KL)  image grThe exclusion criteria were: (1) patients who had undergone knee surgery, (2) patients who had undergone intra-articular injection treatment within 3 months before the study treatment, (3) patients who could not complete the data collection form, and (4) patients with ear eczema or a history of any ear surgery.2.2The control group received routine rehabilitation treatment. In both groups, the patients required NSAIDs during treatment and follow-up; this was prescribed as oral celecoxib  as an anti-inflammatory and for pain relief, one tablet twice a day. Functional exercises were prescribed: isometric training, e.g., straight leg raising and plantar dorsiflexion as the main methods for enhancing muscle strength when the pain was severe or in the acute stage. Joint loosening training included femoral-tibial and proximal tibiofibular joint long-axis traction, patellofemoral lateral and up-down sliding, patellofemoral joint separation, lateral horizontal pushing of the femorotibial joint, patella sliding, and knee extension swings . Each ofThe treatment group received auricular point bean-pressing therapy based on the rehabilitation treatment. For auricular disinfection, a cotton swab was pressed onto the acupoints Fig. A. Four a2.3To assess the efficacy of treatment on knee function and pain, the WOMAC index scores , the paiThe WOMAC is used mainly to evaluate the degree of KOA in patients. The scale includes three dimensions: pain, stiffness, and joint function, with 24 evaluation items. A five-grade scoring method was adopted, and each item was scored from 0 to 4 points according to severity (maximum score: 96 points). The higher the score, the more serious the condition.The VAS scale comprised a 100-mm-long line with anchoring descriptors. The patient marked the line to indicate their pain perception, and the result was expressed as the distance from the left end point to the marked point (in mm). The maximum score was 10 points. The lower the score, the better the pain relief effect.The CRP level with high sensitivity can provide effective information for many types of chronic diseases, and its value greatly increases in the early stage of inflammation. In the present study, 5 mL of fasting venous blood was collected from the patient in the morning and centrifuged at high speed. Serum was obtained, and the CRP value was detected by radioimmunoassay.2.4We used SPSS™ Statistics v25.0 software  for all data processing. The data with normal or approximately normal distribution were expressed as mean 3.3.1Of the 107 patients sampled in this study, 7 did not meet the inclusion criteria, and 3 were excluded based on the above clinical criteria. None of the patients refused to provide informed consent or undergo continued treatment. Follow-up was discontinued for 4 patients for personal reasons Fig. . Of the 3.2After 4 weeks of treatment, the swelling, pain, mobility score, and CRP of the knee joints in the treatment group were significantly lower than those in the control group . The study was approved by the ethics committee of the Wenzhou Hospital of Traditional Chinese Medicine Affiliated to Zhejiang University of Traditional Chinese Medicine .The study was supported by Wenzhou Basic Scientific Research Projects (No. Y20190732).All patients provided signed informed consent for their inclusion in the research.Conception and design of the research: Yeyan Lin, Xuelai Zhou.Acquisition of data: Yeyan Lin, Bin Shen.Analysis and interpretation of the data: Yeyan Lin, Cunxian Lv.Statistical analysis: Yeyan Lin, Yongqin Wu.Obtaining financing: Xuelai Zhou.Writing of the manuscript: Yeyan Lin.Critical revision of the manuscript for intellectual content: Yeyan Lin.All authors read and approved the final draft.


Caudal epidural steroid injection (CESI) has been increasingly used for treating lower back pain. However, there is still significant controversy about the efficacy and safety of different imaging techniques used to guide CESI. In this context, the objective of this study is to compare the efficacies of fluoroscopy- and ultrasonography-guided CESI in patients with chronic lower back pain.The population of this retrospective, observational study consisted of all consecutive patients who underwent CESI for lower back pain between 2018 and 2020. Of the 371 patients included in the study sample, 192 had undergone fluoroscopy-guided CESI (Group F) and 179 ultrasonography-guided CESI (Group U). Patients’ pain and functional statuses were evaluated using the visual analog scale (VAS) and Oswestry Disability Index (ODI) immediately before (baseline) and after the procedure (postintervention day 0-D0), during the second week (D15), the first month (D30), and the third month (D90) after the procedure.The mean age of Group F was significantly higher than that of Group U (p < 0.001). The number of patients with lumbar disc hernia was significantly higher in Group U, whereas the number of patients with spinal stenosis and lumbar disc hernia + spinal/lumbar stenosis was significantly higher in Group F (p = 0.001). The baseline and D0 ODI scores were significantly lower in Group U than in Group F . There was no significant difference between the groups in other VAS and ODI scores (p > 0.05). Intragroup analyses revealed significant reductions in VAS and ODI scores over the follow-up period till D30 compared to the baseline scores in each group (p < 0.001). The decrease recorded in the ODI score between the D15 and baseline measurements was significantly higher in Group F than in Group U (p = 0.006).The study findings indicated that ultrasound-guided CESI was as effective as fluoroscopy-guided CESI in treating chronic lower back pain. Chronic lower back and leg pain are widespread problems that adversely affect the quality of life. The most common causes of chronic lower back pain and leg pain are lumbar discopathies, including lumbar disc herniation and spinal stenosis  –4.Various conservative treatment strategies, including resting, oral medication, physical therapy, and lifestyle modifications, are recommended to overcome lower back and leg pain ,6. In adAccurate localization of the sacral hiatus is the most critical aspect of an injection, regardless of the approach being used ,11–13. THowever, given the difficulty in localizing the sacral hiatus and accurate insertion of the needle into the epidural space, palpation of the posterior superior iliac crest, as a blind technique, reportedly failed in up to 38.5% of the cases ,16. AlteIn this context, this study was carried out to compare the advantages and disadvantages of fluoroscopy- and US-guided CESI in patients with chronic lower back pain.This retrospective, observational study was carried out in the Department of Neurosurgery, Kahramanmaraş Sütçü İmam University Medical Faculty Hospital, Maraş, Turkey, between 2018 and 2020. All procedures involving human participants were carried out in accordance with the ethical standards of the institutional and/or national research committee, the 1964 Declaration of Helsinki, and its later amendments or comparable ethical standards. The study protocol was approved by the Clinical Studies Bioethics Committee of the Medical Faculty of Kahramanmaraş Sütçü İmam University . The written consent could not be taken from the patients due to the retrospective design of the study and unanimity of data.The study population consisted of all consecutive patients aged 18 years or above who underwent CESI for lower back pain in the Department of Neurosurgery, Kahramanmaraş Sütçü İmam University Medical Faculty Hospital, Kahramanmaraş, Turkey, between 2018 and 2020. The study inclusion criteria were having been diagnosed with facet joint hypertrophy, canal stenosis due to hypertrophy of ligamentum flavum, or disc hernia diagnosed using lumbar magnetic resonance imaging, having undergone fluoroscopy or US-guided CESI for chronic lower back pain after no improvement was obtained with conservative treatment, and having been followed up for at least three months. On the other hand, patients who underwent conventional open surgery for lumbar discopathies, patients with missing data, neurological deficits associated with the underlying pathology, cauda equina syndrome, chronic peripheral neuropathy, arterial vascular disease, degenerative spondylolisthesis, facet arthrosis, hip osteoarthritis, congenital or degenerative lumbar spinal stenosis, concurrent infections and malignancy, coagulopathy, allergy to iodinated contrast or medications, pregnancy, and pain for less than six weeks were excluded from the study . In the As an institutional policy, patients were evaluated immediately before (baseline) and after (postintervention day 0-D0) the procedure, during the second week D15), the first month (D30), and the third month (D90) after the procedure. The visual analog scale (VAS)  and Oswe, the firThe 100 mm-long standard VAS is a self-report scale scored between 0 (“no pain”) mm to 100 mm (“the worst pain”). The ODI involves administering a questionnaire that addresses the impairment in performing daily activities due to lower back pain. ODI consisted of ten items. Each item is assigned a score between 0 (“the least amount of disability”) and 5 (“the most severe disability”). These scores were added and then multiplied by two to obtain the overall ODI score [The CESI procedure was performed while the patients were in the prone position in the operating room by placing a cushion beneath the abdomen for optimal imaging. All CESI procedures were performed by experienced neurosurgeons . During the interventions, the patients were monitored via pulse oximetry, blood pressure, and electrocardiography. Intravenous (IV) midazolam and fentanyl were used to obtain sedative anesthesia.The skin overlying the sacrococcygeal area was prepared using iodine-based antiseptic solutions followed by local anesthesia application with 4 mL of prilocaine diluted in 10 mL of saline solution. A 20-gauge, 90-mm spinal needle with its stylet was inserted just below the sacral hiatus at a 45° angle till the bony tissue. The needle was slightly withdrawn and then advanced further to enter the sacral canal.A monoplanar fluoroscope  was used to perform fluoroscopy-guided CESI. The position of the needle in the caudal epidural space was confirmed via a lateral fluoroscopic view. After negative aspiration, 1 mL of contrast medium  was injected. Antero-posterior and lateral radiographic views were used to exclude intravascular, intrathecal, and/or soft tissue infiltration .A linear 9 MHz probe  was used to perform US-guided CESI. The position of the needle was confirmed by the probe’s longitudinal placement to the vertebral axis .A mixture of 8 mL 0.5% bupivacaine hydrochloride 40 mg), 2 mL dexamethasone (4 mg/mL), and 10 mL normal saline was used for epidural injections. This mixture was slowly injected into the epidural space at a rate of 10 mL/min. The patients were discharged after they were allowed to recover in the postanesthesia care unit for one hour [0 mg, 2 mThe descriptive statistics obtained from the collected data were expressed as mean ± standard deviation and median with minimum–maximum values or interquartile ranges values in the case of continuous variables with and without normal distribution, respectively. Additionally, categorical variables were expressed as numbers and percentage values. The Shapiro–Wilk, Kolmogorov–Smirnov, and Anderson–Darling tests were used to analyze the normal distribution characteristics of the numerical variables.The independent samples t-test and the Mann–Whitney U test were used to compare two independent groups where numerical variables conformed (age) and did not conform (VAS and ODI scores) to the normal distribution, respectively.Pearson’s chi-squared test was used to compare the differences between categorical variables (sex and diagnosis) in 2 × 2 tables.The Kruskal–Wallis test was used to compare more than two independent groups in terms of diagnoses where numerical variables did not conform to the normal distribution. In addition, the Dwass–Steel–Critchlow–Fligner test was used to evaluate the differences between the groups in terms of diagnoses.The Friedman test was used to analyze the changes in VAS and ODI scores over the study period. The Durbin–Conover test was used to perform multiple comparisons in order to find significant pairwise relationships.https://www.jamovi.org) and JASP 0.17.1  software packages were used in the statistical analyses. The probability (p) statistics of ≤0.05 were deemed to indicate statistical significance.Jamovi project 2.3.24  . On the Intragroup analyses revealed significant reductions in VAS and ODI scores over the follow-up period till D30 compared to the baseline scores in each group (p < 0.001) .The D90 VAS and ODI scores were significantly higher than D30 VAS and ODI scores  and 3.The percent (%) changes in VAS and ODI scores recorded between different endpoints and at the baseline are summarized in There was no significant difference between the groups in the percent changes in ODI scores assessed over the study period compared to the baseline values (p > 0.05) , except There was also no significant difference between the groups created based on different diagnoses in the percent changes of the VAS and ODI values assessed over the study period compared to the baseline values (p > 0.05) , except The study findings, including the improved pain (VAS) and clinical assessment (ODI) scores assessed during the pre- and postinterventional acute and chronic follow-up periods up until 3 months after the intervention indicated that US-guided CESI was as effective as fluoroscopy-guided CESI in treating chronic lower back pain.Invasive interventional techniques are recommended in cases where conventional and conservative techniques fall short in achieving functional recovery in patients with chronic lower back pain. Among these techniques, CESI has gained popularity given its feasibility and safety for treating chronic lower back pain . CorticoSeveral studies have comparatively addressed the two most frequently used CESI techniques, i.e. fluoroscopy- or US-guided CESI ,18,23,30The self-reported questionnaires are the most widely used common data collection tools for evaluating the functional limitations in patients with chronic lower back pain. Among these tools, VAS assesses pain intensity ,17,19,23Some studies stratified the outcomes of different CESI techniques according to the type of disc pathology ,20 and sIn addition to being the first study on the subject and the large sample size, which may be deemaed the study’s primary strength, there were also some limitations to the study, the most important being its retrospective design. Secondly, the lack of randomization in selecting the CESI technique and significant differences between the patient groups in demographic and clinical characteristics may be deemed other limitations of the study. Thirdly, the 3-month follow-up period might be insufficient to evaluate the long-term outcomes of different CESI techniques.The study findings indicated that US-guided CESI was as effective as fluoroscopy-guided CESI in treating chronic lower back pain. In addition, the fact that patients undergoing US-guided CESI are not exposed to radiation renders it superior to fluoroscopy-guided CESI.