Propofol-induced injection pain is a common adverse effect during the induction of general anesthesia. The purpose of this study is to investigate the effect of low-dose esketamine in preventing propofol injection pain.  In this double-blind, randomized, controlled trial, patients scheduled for elective ear surgery under general anesthesia received either normal saline (NS), or 40 mg lidocaine, or 0.15 mg/kg esketamine 30 seconds before manual injection of propofol. The primary outcome of this study was the incidence of propofol injection pain. The secondary outcomes included injection pain score, vital signs, total dosage of vasoactive drugs used within 5 minutes after induction, and adverse events related to drugs. P < 0.05); however, no significant difference was found between the esketamine and lidocaine groups. The median of injection pain score was significantly lower in the esketamine and lidocaine groups (both median (interquartile range) = 0 (0–1)) than that in the NS group (1 (0–2); P < 0.05). In addition, compared with the NS and lidocaine groups, preinjection esketamine provided more stable hemodynamic parameters within 5 minutes after induction (P < 0.05). No statistical difference was found in adverse events among the three groups.  A total of 105 patients were included. Compared with the NS group (67%), pretreatment with esketamine and lidocaine significantly reduced the incidence of injection pain to 29% and 33%, respectively . Pretreatment with a low-dose esketamine can not only reduce the incidence of propofol injection pain but also provide a more stable circulation in patients after anesthesia induction. This convenient, well-tolerated, and economic treatment appears as an option to be routinely applied in clinic practice.  Propofol is widely used in the induction of general anesthesia due to its rapid onset and early recovery without accumulation; however, pain is a common adverse effect during propofol injection . The incMany strategies have been adopted to prevent injection pain , 4–6. AmFrom a clinical point of view, pharmacological interventions, which only require drug injection as an adjunctive treatment prior to propofol, are more convenient and feasible to be implemented than the venous occlusion technique. Ketamine exerts its sedative and analgesic effects through activating N-methyl-D-aspartate (NMDA) receptor. Previous studies have reported that a small-dose intravenous ketamine could effectively reduce propofol injection pain in adults and children to different degrees –10; howeConsidering the advantages of pharmacological intervention in the clinical setting, we designed this trial to compare the effect of a low-dose esketamine with normal saline (NS) and lidocaine in preventing propofol injection pain.ChiCTR2100052742). The authors prepared this study in accordance with the Consolidated Standards of Reporting Trials (CONSORT) guidelines.This study was conducted as a randomized, double-blinded, controlled trial at Shanghai Eye and Ear, Nose, and Throat (ENT) Hospital of Fudan University. Ethical approval for this study  was provided by the Ethical Committee of Shanghai Eye and ENT Hospital of Fudan University  on December 22, 2020. The experiment was conducted with the patients' understanding and consents. The trial was registered with China Clinical Research Information Service  grade I or II, scheduled to undergo elective ear surgery were included. Patients were excluded if they were allergic to experimental drugs, had a serious risk of increased blood pressure (quiet blood pressure >170/100 mmHg) or intracranial pressure, had a history of hyperthyroidism, serious functional insufficiency of important organs, significant ischemic heart disease, sinus tachycardia, abuse of alcohol, analgesia, or sedative antidepressant.Eligible adult patients were randomly assigned into three groups with 35 patients in each group by computer-generated allocation. A specific anesthesia nurse who did not participate in this study generated a random allocation sequence and enrolled participants. The patients in group NS, group lidocaine, and group esketamine received pretreatment with NS, 40 mg lidocaine, and 0.15 mg/kg esketamine , respectively. The results of randomization were sealed in a closed envelope until the day of surgery. The patients and the participating anesthesiologists were both blinded to the results of randomization. The drugs were prepared in a 20 ml syringe with either 20 ml of NS or 40 mg lidocaine, or 0.15 mg/kg esketamine, by a specific anesthesia nurse who did not participate in this study.2). Subsequently, a 20 G intravenous cannula was inserted at the hand dorsum. After preoxygenation, the patients were pretreated with different agents intravenously 30 seconds before injection of 1% propofol medium-chain triglyceride (MCT) and long-chain triglyceride (LCT) emulsion . After pretreating the agents, propofol were manually injected 2 mg/kg (the dosage was based on lean body weight for obese patients) over 15 seconds. The patients were asked the degree of pain at 5 seconds after injection, and the researchers observed facial expressions and body movements and recorded pain scores. All of them were in deep sedation and unable to give a clear response. Then, the patients were injected with sufentanil 0.1 μg/kg and rocuronium 0.6 mg/kg for the induction of general anesthesia, followed by laryngeal mask (LMA) intubation. Dorasetron 0.35 mg/kg was administered 30 minutes before the end of surgery. After the operation, patients were transferred to the resuscitation room until fully recovered.On arrival in the operating room, the patients received routine monitoring, including electrocardiography, noninvasive blood pressure, and pulse oxygen saturation , a Bonferroni correction was used to adjust the type I error rate for multiple comparisons. Continuous variables were presented as median (25th and 75th percentiles) or mean ± standard deviation (SD). Categorical variables were presented as number of patients and percentages. All statistical tests are 2-tailed; the corrected differences were considered significant at P < 0.05.Continuous variables were analyzed by the one-way analysis of variance (ANOVA) test followed by the Dunnett test or Kruskal–Wallis test followed by the Mann–Whitney During the period from November 4, 2021, and February 4, 2022, a total of 105 patients were screened for eligibility and 101 patients were ultimately enrolled and analyzed . In the P < 0.05). However, the number of patients experiencing injection pain was not different between group esketamine and group lidocaine, suggesting that esketamine is just as effective as lidocaine.The incidences of propofol injection pain (pain score of 1 or more) are shown in P < 0.05) (The median of injection pain score in the esketamine and lidocaine groups was both 0 (0-1), which was significantly lower than that in the NS group (1 (0–2);  < 0.05) . The inc < 0.05) .P < 0.05), but had no significant effect on HR (P < 0.05), accompanied with a slight increase in T4, which may be due to the injection of vasoactive drugs (The hemodynamic data measured during 5 minutes within induction are shown in ct on HR . Compareve drugs . In addive drugs . Anestheve drugs .The cumulative dosage of phenylephrine during 5 minutes after induction was lower in the esketamine group compared with that in the NS and lidocaine groups; however, this did not reach a statistical significance .The distribution and incidence of adverse events in each group are given in In this study, we found that a low-dose esketamine at 0.15 mg/kg was as effective as lidocaine in attenuating propofol injection pain compared with NS. However, esketamine was more beneficial in providing a stable hemodynamic profile than lidocaine and NS during induction.A previous study reported that ketamine reduced propofol injection pain from 84.8% to 17% at a dosage of 0.3 mg/kg . ConsideThe major mechanism responsible for pretreatment with ketamine 30 seconds before propofol may be through peripheral local anesthetic action in the vascular endothelium, rather than a central analgesic effect . The exaPrevious studies have shown that a combination of propofol and ketamine is more beneficial for maintaining hemodynamic stability due to the cardiostimulant effects of ketamine balancing the cardiodepressant effects of propofol –16. ConsIt is well known that the use of ketamine as a single sedative agent has been limited by its psychotomimetic effects and other side effects . Our datIn our study, pretreatment with esketamine not only reduced the incidence of pain injection but also provided a stable hemodynamic profile after induction. From a clinical point of view, premedication with esketamine is easy and convenient to be implemented as well as economic wise in daily practice. The results of this study can be clinically applied in general.A limitation of our study is that the propofol injection cannot be eliminated completely. An optimal dosage of esketamine for propofol injection pain should be further examined. Furthermore, this study was only conducted at a single center. In the future, we will coordinate with different hospitals to evaluate the effects of esketamine on propofol-induced injection pain.The present study showed that pretreatment with low-dose esketamine at 0.15 mg/kg can relieve propofol-induced injection pain effectively and safely. Furthermore, 0.15 mg/kg esketamine can also provide more stable hemodynamic parameters during induction. Conclusively, pretreatment with a low-dose esketamine appears as a convenient, well-tolerated, and economical option used during the induction of anesthesia. The results of our study provide evidence for improving clinical practice with a positive impact on patient care.


Background: The COVID-19 outbreak disrupted medical access for patients receiving chronic opioid therapy. This study investigated their prescription opioid dosages before and after the 2020 outbreak in Taiwan. Methods: A prospective questionnaire survey was conducted among registered outpatients receiving long-term opioids before July 2019 in Taiwan. The questionnaire included items from the Taiwanese Brief Pain Inventory and quality of life assessment. Follow-up surveys in outpatient departments through October 2020 were conducted to collect opioid prescription data. Results: After a mean of 531 days, the questionnaire responses of 103 of the initial 117 respondents were reviewed. Daily opioid doses decreased for 31 respondents (30.1%), remained roughly equivalent (defined as ±2.5%) for 27 (26.2%), and increased for 45 (43.7%) after the first wave of the pandemic. The use of strong opioids and nonopioid medications did not significantly differ among the three groups, but less fentanyl patch use was noted in the decreased-dose group after the outbreak. More than 70% of the patients received daily high-dose opioids ; moreover, 60% reported constipation. No deaths due to opioid overdose occurred during the study period. Conclusions: The COVID-19 outbreak in 2020 did not interrupt access to long-term opioid prescriptions for most registered patients with chronic pain in Taiwan. Less fentanyl patch use was observed in participants whose opioid dose was tapering. CDC Guideline for Prescribing Opioids for Chronic Pain [CDC Clinical Practice Guideline for Prescribing Opioids—United States, 2022 and the release of the final updated guideline is anticipated in late 2022 [The United States and Canada have faced an opioid crisis for the past two decades. The 2011 Canadian guidelines for safe opioid use defined a “watchful” daily dose of 200 morphine milligram equivalents (MMEs) as requiring careful reassessment [nic Pain , 20% in nic Pain . In Febrate 2022 .Since March 2020, the COVID-19 pandemic and associated lockdowns have increased morbidity risks, mortality risks, and healthcare utilization among patients with chronic pain , as wellFollowing the Anglo–Sino Opium War in the 1840s, the use of opioids had been prohibited in China. Until 2011, more than 70% of Taiwanese physicians perceived physician reluctance as a leading barrier to prescribing opioids for chronic pain . In TaiwThe first COVID-19 outbreak in Taiwan was well controlled. There were only 447 laboratory-confirmed cases before 30 June 2020, , includiA prospective multicenter questionnaire survey was initially administered to registered outpatients receiving long-term opioids for CNCP in Taiwan between October 2018 and July 2019 . A “longThis study used a Chinese-language questionnaire incorporating elements from several existing inventories ,21,22, nA follow-up survey was scheduled to be conducted 1 year after the initial questionnaire investigation; however, it was postponed because of the COVID-19 outbreak in January 2020. Because of restricted hospital entry and exposure concerns in Taiwan, the follow-up survey was truncated to the collection of opioid prescription data by pain medicine specialists in the outpatient departments, continuing through October 2020, after the first wave of the pandemic. The doses at follow-up were compared with the corresponding prepandemic doses, and the patients were arbitrarily divided into three groups consisting of those receiving a decreased daily dose (greater than 2.5%), an equal daily dose (±2.5%), or an increased daily dose (greater than 2.5%). The threshold for a “high” daily dose was defined as ≥200, ≥90, or ≥100 MMEs on the basis of the 2011 Canadian guideline , respectU test were used to compare opioid and nonopioid medications, side effects, depression scores, and quality of life scores among the groups . Categorical variables were compared using the chi-squared test or Fisher’s exact test. In all cases, a p value of <0.05 was considered statistically significant.Demographic data are presented as means ± standard deviations. Questionnaire responses were analyzed using SPSS version 22 . The Kruskal–Wallis one-way analysis of variance (ANOVA) and Mann–Whitney Of the 117 patients who responded to the first questionnaire in 2019, 103 (88.0%) were reviewed at the outpatient departments in the follow-up survey after the COVID-19 outbreak in 2020. Fourteen (12.0%) patients were excluded; three died of underlying diseases (not opioid overdose), five were referred to other specialists, and six were lost to follow-up .p = 0.010) than in the other two groups.p = 0.013; from five patients before the outbreak to one patient receiving 28.8 MMEs after the outbreak).As indicated in p = 0.010 and 0.002, respectively); in contrast, zero patients did so in the equal-dose group.As presented in To the best of our knowledge, this is the first prospective longitudinal study examining long-term opioid prescriptions among registered patients with CNCP in Taiwan before and after the COVID-19 outbreak. Of the 103 patients surveyed after the first wave of the pandemic, 30% had a median reduction of 60 MMEs, whereas 43.7% had an increase of 55.7 MMEs. We observed decreased usage of the fentanyl patch in the decreased-dose group after the outbreak. However, we noted no other differences in the use of other strong opioids or nonopioid medications between the decreased-dose group and the equal-dose and increased-dose groups. Daily high-dose opioids (≥90 MMEs) were prescribed to 70% of all the patients after the outbreak in 2020.Multimodal therapy is optimal for managing chronic pain. However, pharmacological, physical, and psychological treatments for chronic pain were disrupted by the COVID-19 pandemic. In the Chronic Pain & COVID-19 Pan-Canadian Study, 38.3% and 68.3% of patients reported changes in their pharmacological pain treatment and self-management strategies, respectively, during the early pandemic period of 2020 . Lack ofn = 3656, or 15.5 per 100,000 people) in 2020 [The recognition of an opioid crisis in the United Sates in October 2017 signified a public health emergency . Drug ov in 2020 , but thiChronic pain, daily activity limitations, side effects, and resultant socioeconomic factors all contribute to the complexity of low quality of life of outpatients with opioid prescriptions. The WHOQOL-BREF questionnaire is frequently used to evaluate the effectiveness of therapeutic regimens and psychological interventions for chronic diseases . In the This study has several limitations. First, the pain medicine specialists followed up their patients after the first wave of the COVID-19 pandemic in 2020. Six (5.1%) of 117 patients were lost to follow-up, without definite knowledge of their whereabouts, suggesting that the effects of the pandemic on care or opioid misuse may be underestimated among this vulnerable population. In addition, the findings of this study of a limited number of total registered patients with CNCP receiving long-term opioids in Taiwan are not generalizable to other countries with opioid crises. Second, we collected data for opioid prescriptions and nonopioid medications only before and after the first wave of the pandemic; monthly details of all prescriptions were not collected, preventing calculation of tapering rates. Third, because of the pandemic, the scheduled follow-up survey on quality of life and nonpharmacological therapy could not be conducted. To explore the factors potentially contributing to opioid dose reduction or escalation and provide more accurate information on chronic pain management in Taiwan, further studies using the aforementioned surveys are necessary.This study demonstrated that most of the registered patients with CNCP in Taiwan continually received long-term opioid prescriptions during the COVID-19 outbreak in 2020, with 70% of the patients receiving daily high-dose opioids (≥90 MMEs) after the outbreak. Less fentanyl patch use was observed among the patients with opioid dose tapering.


A/L as the cut-off for serum specific-IgE (sIgE) immunoassays, while the detection limit is 0.1 KUA/L. The clinical relevance of -low-level sIgE (0.1–0.35 KUA/L) remains controversial. Pru p 3 sIgE is considered to be the main routine tool for assessing lipid transfer protein (LTP) sensitization. We aimed to evaluate the clinical relevance of Pru p 3 sIgE low levels in a population diagnosed with LTP allergy. Adults diagnosed with LTP allergy and Pru p 3 sIgE ≥ 0.1 KUA/L between 2012 and 2019 were included. Clinical data were reviewed. nPru p 3 basophil activation test (BAT) was performed and basophil reactivity (BR) and sensitivity (BS) correlated with the peach allergy symptoms. Pru p 3 sIgE from 496 subjects was recorded, 114 (23.0%) between 0.1 and 0.34 KUA/L (grLOW), the rest ≥ 0.35 KUA/L (grB). A total of 44.7% in grLOW and 59.9% in grB were allergic. Urticaria was more frequent in grLOW. In grLOW, Pru p 3 sIgE was higher in patients with local compared with systemic symptoms. In grB, Pru p 3 sIgE was higher in allergic patients. Pru p 3/Total IgE ratios were higher in allergic vs. tolerant in both groups. In BAT, BR was similar in both groups. In grLOW, it was higher on allergic compared with tolerant (p = 0.0286), and on those having systemic vs. local symptoms (p = 0.0286). BS showed no significant difference between groups. Patients with low levels represent a non-negligible fraction and around 45% are peach allergic. BAT showed functional sIgE in them. Pru p 3 sensitizations should be carefully evaluated even when sIgE levels are low.Many clinical lab settings still use 0.35 KU A/L; and it is still used in many clinical lab settings, despite the reports showing that the cut-off may differ depending upon the factors, such as the allergenic source and patient age (in vitro singleplex fluorescence enzyme-immunoassay ImmunoCAP® (ThermoFisher Scientific) is 0.10 KUA/L. Little evidence has been reported on the clinical relevance of sIgE levels between 0.1 and 0.35 KUA/L and it is a matter of discussion in the field.Allergen-specific IgE (sIgE) levels cannot be used as individual predictors of clinical reactivity or severity, although high-sIgE concentrations correlate with increased risk of reactions . The impient age . Indeed,A/L to discriminate patients at risk of reactions (A/L (Lipid transfer proteins (LTPs) are widely cross-reacting panallergens related to complex clinical profiles regarding severity and food triggers , 6. LTPseactions , but otheactions . Neverthons  is measured per protocol in all LTPs allergic patients regardless of the presence of symptoms with peach. Sensitization to other plant food allergens was analyzed by microarray ImmunoCAP® ISAC (Thermo Fisher Scientific.) Patients sensitized to other panallergens  were excluded. The study was approved by the local ethic committee (HCB/2020/0373).Adult patients evaluated in the Allergy Section of Hospital Clinic  between 2012 and 2019 with an LTPs food allergy and Pru p 3 sIgE ≥ 0.1 KUDemographical and epidemiological data were retrospectively recorded from clinical history. Peach allergy symptoms were classified as: local  and systemic . Peach tolerance (–TOL-) and peach avoidance  were also recorded and also the involvement of cofactors, including exercise, alcohol, non-steroidal anti-inflammatory drugs (NSAIDs), and/or menstruation.TM kit  and following the manufacturer's procedures. Purified Pru p 3  was tested at 25, 12.5, 5, and 2.5 ng/ml final concentrations. Basophils were identified by flow cytometry . A minimum of 500 basophils was gated and those CD63+ were defined as activated (≥15% was considered a positive test). Basophil reactivity  was calculated as the CD63+ expression post-stimulus minus basal CD63+ expression, represented as % CD63+. Basophil sensitivity (BS) is calculated as CD-sens, i.e., inversion of EC50 (concentration inducing 50% of maximum response) × 100 (Pru p 3 basophil activation test (BAT) was performed in some patients to assess sIgE functionality. Briefly, after the patient informed consent, 10 ml of heparinized peripheral blood was obtained and immediately taken to the laboratory for BAT using the Flow2CASTe) × 100 .U-test or the Kruskal–Wallis test. Qualitative data were compared using the chi-squared test and Fisher's exact test for a small sample size. P values lower than 0.05 were considered statistically significant. The GraphPad Prism 8.0.2 software  was used for the statistical analysis.Pru p 3 sIgE centralization and dispersion measurements were calculated considering a quantitative and asymmetric distribution. Free distribution was considered in our analysis so non-parametric tests were used to verify heterogenicity between our variables. Quantitative data were compared using the Mann Whitney A/L were recorded between 2012 and 2019. A total of 284 (57.3%) subjects were women, median  age of 42 (17–92) years. Of 496 subjects, 114 (23.0%) had Pru p 3 sIgE between 0.1 and 0.34 KUA/L (grLOW = group low levels) and 382 (77.0%) ≥ 0.35 KUA/L (grB = group high levels).A total of 496 subjects with Pru p 3 sIgE ≥ 0.1 KUp > 0.05), with similar peach-related symptoms and a higher presence of local symptoms. However, U/AE was more frequent in grLOW (p = 0.020). Peach avoidance was statistically superior in grLOW (p < 0.0001)  .p < 0.05), whereas no differences were observed in Pru p 3/Peach sIgE (ratio) between groups (p = 0.0385). In grB (p = 0.0009). The medians from the ratios Pru p 3/peach sIgE were superior to 1 for either grLOW or grB. Moreover, when classifying patients according to their clinical symptoms, no statistically significant differences were found. Pru p 3/Total IgE ratios were lower than 1% in grLOW, unlike grB. In both groups, these ratios were statistically higher (p < 0.0001) in allergic compared to tolerant  reactive sIgE may cause false-positive results in Pru p 3 measurements by binding the test cellulose matrix . CCD senA/L. The ratio Pru p 3/peach sIgE median was 0.99 [0.79–1.09]. In addition, from these BAT- patients were 0.21 [0.18–0.23] (Pru p 3 sIgE) and 0.98 [0.97–0.99] (Pru p 3/peach sIgE ratio). BAT reactivity  was not statistically different between groups (BR median: 17.8% grLOW/ 27.3% grB), neither when only allergic patients of each group were compared. In grLOW, BR was significantly higher on allergic individuals vs. tolerant ones (p = 0.0286), and on those having systemic symptoms vs. local (p = 0.0286). No statistically significant differences in basophil sensitivity were found between groups, although being higher in grLOW (CD-sens median: 819.0 grLOW/ 75.4 grB).nPru p 3 BAT was performed on 12 patients per group as previously reported . All in In summary, the ratio Pru p 3/Peach was similar in both groups and superior to 1, which would confirm a sensitization due to Pru p 3 on our population . About 4Besides the theory reported by Kleine-Tebbe and Jakob  exposingA definite answer for the reason why Pru p 3 sIgE levels are higher on patients with local symptoms compared with those with systemic is not clear. Little is known about the real correlation between LTP sIgE levels and symptoms severity, and conflicting results have been published , 16, 17.Moreover, it has been described that mono-sensitization to LTP correlates with a more severe clinical reactivity  which coIn the previous studies from our group and collaborators –23, a trCCD sensitization was similarly distributed in both the groups, ruling out that low levels detected were merely artifacts of CCD interaction not deserving clinical consideration.Finally, a lower co-sensitization to other LTPs was found on grLOW although sensitization profiles  were similar in both the groups. This study has some limitations, besides being retrospective. Mainly, oral food challenges could not be done to confirm food diagnosis due to logistic limitations; and the fact that avoidance may have caused sIgE concentrations to decrease in patients with a history of a severe reaction.In conclusion, our data show that, regardless of patients with low Pru p 3 sIgE may represent a minority in our daily practice, this sensitization can be clinically relevant, with up to 20% of systemic reactions. Therefore, Pru p 3 sensitizations should be carefully evaluated even when sIgE levels are low.The original contributions presented in the study are included in the article/The studies involving human participants were reviewed and approved by Hospital Clínic de Barcelona Ethical Committee. The patients/participants provided their written informed consent to participate in this study.SB-V has contributed to the acquisition, analysis, and interpretation of data, as well as drafting the manuscript for publication. RC-S and MR-Z have contributed to the acquisition of clinical data. CS, JR, and MT contributed to the performance of laboratory tests. JB, RM, and MP have contributed to the design and interpretation of the data and critically revised. All authors have participated sufficiently in the work, approved the final version, agreed to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. 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The Avoidance-Endurance Model distinguishes between subgroups of low back pain (LBP) patients with three maladaptive styles of coping with pain: fear-avoidance (FAR), distress-endurance (DER), eustress-endurance (EER), and one adaptive coping style (AR). This study aimed to compare the quantity of patients' perceived psychosocial stressors and coping resources across these subgroups.This cross-sectional study was conducted at an outpatient rehabilitation center for patients with chronic musculoskeletal pain. One hundred and thirty-seven patients (69 women/68 men) with chronic LBP were assessed using the following: a demographic checklist, the visual analogue scale, Avoidance-Endurance Questionnaire, Roland-Morris Disability Questionnaire, Pain Disability Index, and 36-Item Short Form. Subsequently, patients participated in semi-structured interviews led by clinical psychologists, which were intended to identify their perception of stressors and coping resources. The quantity of psychosocial stressors and coping resources were analyzed using deductive and inductive content analyses and then compared between subgroups using chi-square-tests.p = <0.001) and “other workplace problems” compared to ARs and EERs (p = <0.001). DERs reported significantly higher levels of “mental suffering” (p = <0.001), “job stress” (p = 0.022), and “familial losses” (p = 0.029) compared to ARs, whereas the AR group demonstrated significantly more “coping resources” (p = 0.001) compared to FARs.FARs experienced significantly higher levels of “mental suffering” (AEM-subgroups differed in the quantity of perceived psychosocial stressors and coping resources with AR, who demonstrated a lower risk for pain chronicity and reported the highest quantity of resources. The variability across subgroups may imply differences in patientś needs regarding therapeutic interventions and suggests that a resource-centered approach to cope with stress and pain may be beneficial. The Avoidance-Endurance model (AEM) distinguishes between four different pain coping patterns in persons afflicted with low back pain (LBP): patients with fear-avoidance (FAR), eustress-endurance (EER), distress-endurance (DER), and adaptive pain response patterns (AR) . The thrNext to the aforementioned three maladaptive pain response patterns, acute or chronic stress is an important risk factor for pain chronicity. Lazarus and Folkman defined stress in the cognitive-transactional model: first, a person subjectively evaluates whether a situation is dangerous, positive, or neutral (mostly on an unconscious level); second, the person assesses his or her internal  or external resources  to cope with the situation . Only ifSince strategies to cope with both stress and pain (such as AEM patterns) are important contributors to the maintenance of LBP, it is surprising that little research has investigated whether there are associations between and common features across these strategies. Research to date has found that FAR is associated with work absences and disabilities at work , 31, wheIn order to further understand the role of perceived psychosocial stressors and their relevance to groups of different LBP response patterns, this study sought to compare the quantity of patients' psychosocial stressors and coping resources across these subgroups. We hypothesized that patients with maladaptive pain response patterns  would report higher levels of mental suffering and perceived work- and family-related/social stressors compared to ARs and EERs and less coping resources compared to ARs.This study builds upon a study published in 2017  by provi2. After screening for inclusion and exclusion criteria, a total of 178 CLBP patients were eligible for inclusion in the study. All patients received oral and written information about the study and signed a consent form. The study protocol was approved by the ethics committee of the city of Vienna .Between January 2012 and July 2015 all patients who sought treatment for LBP and were referred to the outpatient physical medicine and rehabilitation center were asked to participate in a study. Of these, 216 patients agreed to participate in this cross sectional study. The inclusion criteria were: pain in the lower back with and without radiation lasting for more than three months  at a minPatients with CLBP were assessed once using the following questionnaires and interviews.The patients’ gender, age, education level, marital status, and pain history were all assessed with a general sociodemographic and medical history checklist. Current pain intensity was rated on visual analogue scales (VAS) ranging from 0 (no pain) to 100 (highest pain) . The VASThe German version of the Roland-Morris disability questionnaire (RMDQ) measures LBP-related functional disability . The RMDThe Pain Disability Index (PDI) assesses experienced pain-related disability in seven life domains measured on 11-point rating scales  . The sumAvoidance-endurance behaviour was measured with the Avoidance-Endurance Questionnaire (AEQ) , which cHalf-standardized, semi-structured interviews  led by cz-scores to provide standardized scores for subsequent cluster analysis. Based on an input distance matrix (Euclidean distances) a single-linkage hierarchical clustering was applied to detect and subsequently eliminate outliers. After removing the outliers, a Ward hierarchical clustering was performed to minimize the within-cluster sum-of-squares. To determine the number of clusters, statistical [NbClust package , “familial loss”, and “coping resources”. The inductive category “job stress” subsumed high work-load, time pressure, high responsibility, and lack of possibilities to relax . In the inductive category “other workplace problems”, stressors like dissatisfaction with the workplace, absences because of illness or temporary invalid pension, unemployment, troubles finding a job and a bad working atmosphere were included . The category “familial loss” comprised experiences of loss, separation, and cases of death in the family (representative example: “my mother and my brother both died in the last two years. Due to that nothing brings joy.”). The category “coping resources” comprised internal and external resources such as coping-strategies, social support, and interests/hobbies, etc. . The categories identified through deductive and inductive content analyses were counted for each interview with “true” or “untrue”.p-values were computed by Monte Carlo simulation  of the patients as FARs, 34% (n = 47) as DERs, 17% (n = 23) as EERs and 25% (n = 34) as ARs. The means and SDs of the clustering variables are provided in The cluster analysis classified 24% (n = 10) of the patients were identified as FARs, 19% (n = 26) as DER, 59% (n = 81) as EER and 15% (n = 20) as AR.In the confirmatory analysis 7% (n = 52) of all patients reported that they suffer mentally, 54% (n = 74) reported work-related stress, and 32.1% (n = 44) identified family-related/social stressors. For the numbers divided by AEM-subgroups see V = 0.411, see A total of 39.7%  were identified to be exposed to “job stress”, and 19.08% (n = 25) reported “other workplace problems”. “Familial loss” and accompanying strain was reported by 11.45% (n = 15) of the patients, whereas coping resources in daily life were mentioned by 32.3% (n = 41) of the patients. For the numbers divided by AEM-subgroups, the results of the Pearson`s chi square tests, and significant differences between subgroups see V = 0.266, indicating a weak effect). Moreover, analysis revealed that FARs reported significantly more “other workplace problems” than ARs, and tendentially to EERs . Regarding “familial losses” the DERs reported significantly more “familial losses” compared to ARs . On the other hand, the ARs reported significantly more “coping resources” compared to the FARs , and ARs tended to have more “coping resources” than DERs. The following coping resources were mentioned: Exercising/sports , hobbies/interests , coping with stress/setting boundaries , positive attitudes , social environment , hope/motivation , and external explanatory models .Considering the complete sample studied, 32.85% . Additionally, the group of ARs with the lowest risk of pain chronification , 38 repoRecent evidence conveys that approximately one third of CLBP patients are diagnosed with psychological disorders . Among tThe AEM-groups in this study did not differ in the extent to which they identified job-related strain, even though more than 50% of the total sample study reported job strain, and associations of back pain and work-related stress are consistent with earlier research –21. As jLiterature suggests that both family-related and social stressors have an impact on pain chronification, and family was found to be a highly relevant life value in a sample of CLBP patients . ApproxiIn addition to identifying differences regarding stressors, this study is also highlights the importance of an individual's perceived coping resources. According to the transactional stress model, the determination of a challenging situation as stressful is based on one's appraisal of their own coping resources . Our stuThis study's findings have major implications for goal setting and intervention planning within the different AEM groups of CLBP patients. Cognitive-behavioural interventions have already been evaluated in AEM-subgroups . TherefoDespite its strengths, this study also has certain limitations. The representativeness of the study sample may be limited due to the low to moderate levels of pain and disability of the participants, although such pain intensity levels on the VAS are typical for chronic pain. Some effects were also quite small so that further research is needed to replicate findings. Another limitation is that to make the study feasible, interviews were not recorded, and therefore only written notes are available, as opposed to audio files and complete transcripts for more in-depth exploration. However, additional inductive categories were built to allow a greater insight and understanding of stressors and coping resources of LBP patients. We used a hierarchical cluster analysis to build the AEM-subgroups, which may be influenced by the individual characteristics of the study population. In order to confirm the validity of the subgroup classification we also used a cut-off-method, which in general revealed comparable results. In some cases, the cut-off method revealed different results for FAR and DER groups than what was found through cluster analysis. This variability may be explained by the possibility that DERs alternate between fear-avoidance and endurance behavior, as has been described in the literature , 76. HuiThe findings of our study suggest that patients would benefit from subgroup-specific and resource-centered psychological interventions that target maladaptive coping styles. Future research will, however, have to determine more closely if FARs, EERs and DERs as well as ARs also demonstrate their specific behavior patterns in response to other forms of stress or challenging situations, beyond coping with pain.This study for the first time comprehensively investigated differences in perceived psychosocial stressors and coping resources between groups of chronic low back pain patients as classified by the Avoidance-Endurance Model. The qualitative as well as quantitative research approach serves to overcome shortcomings associated with a solely quantitative approach and thus gives a more detailed insight into relevant psychosocial stressors and coping resources in patients with different pain behaviour patterns. As results show significant differences between groups, they are of high relevance in the context of preventing pain chronification and highlight the importance of individual coping behaviours as well as coping resources. This study thus sheds light on psychosocial dimensions of pain and provides helpful information for health professionals of variable professions regarding individualized therapy planning especially for groups of patients with maladaptive pain coping behaviours. It also stresses the importance of coping resources as protective factors against pain chronification as well as possible starting points for resource-centred therapy.


Patients with osteoporotic vertebral fractures (OVFs) often suffer from residual low back pain (LBP) after percutaneous kyphoplasty (PKP). The purpose of this study was to identify risk factors for postoperative residual LBP and to develop a nomogram to predict the occurrence of residual LBP.We retrospectively reviewed 236 patients who underwent PKP for OVFs and had a minimum follow-up of 12 months. The mean age was 72.1 ± 6.3, 74.3% were female and 25.7% were male. Patients with LBP VAS scores ≥ 3.5 at the 12th month postoperatively were considered to have residual LBP. Risk factors for residual LBP were identified by univariate and multifactorial logistic regression analysis. Then, a predictive nomogram was constructed and validated using the bootstrap method. The discrimination, calibration, and clinical utility of the nomogram were assessed using a receiver operating characteristic curve (ROC), a calibration curve, and a decision curve analysis (DCA).P = 0.02), intravertebral vacuum cleft (P = 0.01), no anti-osteoporosis treatment (P < 0.001), cement volume <3 ml (P = 0.02), and cement distrubution (P = 0.01) as independent risk factors for residual LBP. The area under the ROC was 0.83 (0.74–0.93) and further validated by bootstrap method was 0.83 (0.73–0.92). The calibration curve illustrated the consistency between the predicted probability and the observed results. DCA showed that nomogram exhibits clinical utility and net benefit when the threshold probability is between 6% and 73%.univariate and multifactorial logistic regression analysis identified depression (Our study found that depression, intravertebral vacuum cleft, no anti-osteoporosis treatment, cement volume <3 ml and cement distribution represent independent risk factors for residual LBP. The nomogram containing the above five predictors can accurately predict the risk of residual LBP after surgery. Osteoporotic vertebral fractures (OVFs) result from decreased bone density and bone strength . OVFs maStudies have examined various potential risk factors for residual LBP, such as bone mineral density, intravertebral vacuum cleft, posterior fascia edema, fracture of adjacent vertebral bodies, and vertebral compression ratio , 7, 8. HOur study analyzed multiple baseline factors associated with residual LBP after PKP in OVFs. Furthermore, we developed and validated a nomogram to provide individualized guidance for the treatment of residual LBP.We prospectively collected data from patients treated with PKP for osteoporotic vertebral fractures between May 2019 and June 2021 at a hospital in Tianjin, China. These patients were analyzed retrospectively. The details of the inclusion and exclusion criteria were as follows. Inclusion criteria: (1) The patient had a clear history of osteoporosis or was diagnosed with osteoporosis by DXA. (2) Vertebral fractures caused by low-energy injuries and further confirmed by spinal MRI . (3) OnlThe patient was placed in a prone position, raised to make the abdomen hang, and routinely sterilized. The C-arm machine was used to locate the fractured vertebrae following local anesthesia or general anesthesia. Using pedicle approach, the puncture probe was inserted into the vertebrae. The tip in the lateral fluoroscopy was located in the front 1/3 of the vertebral body and close to or exceeded the midline of the spinous process in the front fluoroscopy. Then, the tube core of the guide needle was removed, and the working channel was established. The inflatable balloon was placed into the working channel, and the contrast medium was slowly injected into the balloon. The balloon was expanded to reposition the vertebral body. The vertebral body was filled with bone cement under continuous fluoroscopic guidance to eliminate the expansion gap. The procedure should be stopped immediately in cases with bone cement leakage. After curing the bone cement, the working channel was withdrawn. Then, the skin incision was sutured, and the cells were observed for 10–20 min. Radiographs and computed tomography (CT) scans of the spine were taken for all patients on the first postsurgical day. All patients were discharged 2 to 3 days after surgery.A visual analog scale was used to evaluate patients' low back pain intensity at the 12th month. Patients' low back pain intensity is the average intensity for the month. A VAS score <3.5 corresponds to mild pain, whereas a VAS score ≥3.5 corresponds to moderate to severe pain and is considered to indicate residual low back pain , bone mineral density (BMD), comorbidities , smoking, and depression. The depression status of patients was determined based on the mental component summary of the Short Form-36 (SF-36 MCS) . SF-36 MThe following baseline clinical and radiological factors were assessed: (1) Time from pain to surgery; (2) Segment location—thoracic spine (T4–T9), thoracolumbar spine (T10-L2), and lumbar spine (L3–L5); (3) VAS score for low back pain; (4) Vertebral height ratio (VHR) and vertebral kyphosis angle (VKA)—The vertebral height ratio is the ratio of the anterior height of the fractured vertebral body to the average anterior height of the adjacent upper and lower segments , and theIntraoperative factors: (1) Anesthesia—local or general anesthesia; (2) Cement volume; (3) Cement distribution—Cement distribution was classified into two states of sufficient and insufficient based on whether the cement filled the majority of the fractured area of the vertebrae ; (4) CemU test according to the data distribution characteristics. Chi-squared or Fisher's exact test was used to investigate differences in categorical data between the two groups. Variables with P value less than 0.05 in the univariate analysis were included in further multifactorial analyses to identify independent risk factors. The nomogram was then developed using independent risk factors. SPSS 26 software  was used for data analysis, and R software  was utilized for nomogram construction. The predictive ability and performance of the model were assessed based on the receiver operating characteristic (ROC) curve, the area under the ROC curve (AUC), the calibration curve, and decision curve analysis (DCA). In general, the AUC values between 0.5 and 1.0 indicate that the model can accurately predict and discriminate , but significant differences existed between the two groups (P < 0.01), as shown in A total of 236 patients were enrolled in this study and completed the 12-month follow-up according to the inclusion and exclusion criteria. Thirty patients were included in the LBP group (VAS ≥ 3.5), and the incidence of residual LBP following PKP was 12.7%. Another 206 patients with a low back pain VAS score <3.5 were included as the non-LBP group. Both groups experienced significant improvement in VAS scores compared with the preoperative scores at the end of follow-up (P = 0.01), intravertebral vacuum cleft (P < 0.01), anti-osteoporosis treatment (P < 0.01), cement volume (P = 0.01), and cement distribution (P = 0.01). None of the other variables differed significantly between the two groups. Multivariate analysis indicates that depression , intravertebral vacuum cleft , no anti-osteoporosis treatment , insufficient cement distribution in the fractured area , and cement volume <3 ml  were independent risk factors for residual LBP, as shown in Univariate analysis results of baseline demographic characteristics, baseline clinical and radiological factors, and intraoperative factors are shown in To predict residual LBP, we developed a nomogram using the predictive factors identified in multivariate analysis . The preIn this study, we analyzed 236 patients with osteoporotic vertebral fractures to identify baseline impact factors for postoperative residual LBP and developed and validated a predictive model to predict the risk of LBP occurrence following PKP. We found that 12.7% of patients experienced residual LBP postoperatively, which is similar to that reported in previous studies , 9. MultSeveral studies have shown that depression can affect pain and function following surgery for musculoskeletal disorders , 16. TheThe pathogenesis of the intravertebral vacuum cleft is unclear. Most studies , 21 tendThe pathological basis of OVCF is osteoporosis, and PKP can help patients relieve pain and regain self-care early. However, the procedure only treats fractured vertebrae and has no therapeutic effect on systemic osteoporosis. Previous reports  have notCement volume and cement distribution in the fractured area are independent predictors of residual low back pain that may be related to the inadequate restoration of vertebral stiffness and strength . With atAfter analyzing potential risk factors, such as demographic characteristics, clinical and radiological factors, and intraoperative factors, we developed a nomogram for predicting residual LBP. Intraoperative interventions can be performed to modify these risk factors in patients, such as the amount and distribution of cement. Additionally, this study emphasizes the need for standardized anti-osteoporosis treatment for OVCF patients after PKP.Our research also has some limitations. (1). Although we collected mean VAS scores for low back pain in patients at the 12th month postoperatively, it is still possible that this low back pain is incidental; therefore, studies with long follow-up periods and multiple follow-up nodes are needed to further validate the findings. (2). Patients have different ranges of pain tolerance, leading to overestimating or underestimating the residual LBP rate. (3). As this was a retrospective study, some confounding factors were unavoidable, such as the patient's preoperative low back muscle mass, daily activities that may contribute to the sensation of low back pain, comorbidity with other underlying conditions, differences in philosophy and technique between surgeons, and the patient's socioeconomic status. (4). We exclusively administered bisphosphonates for anti-osteoporosis treatment, and the effects anti-osteoporosis drugs with different mechanisms of action  on postoperative residual low back pain remain unclear. (5). This study is a single-center study from China, and future multicenter studies in different hospitals, regions, or countries are needed to further validate the findings of this study.Our study found that depression, intravertebral vacuum cleft, no anti-osteoporosis treatment, insufficient cement distribution in the fractured area, and cement volume <3 ml are independent risk factors for residual LBP after PKP treated for OVFs. The nomogram containing the above five predictors can accurately predict the risk of residual LBP after surgery.


Spinal intradural hematoma (SIH) is a rare condition which can cause neurological sequelae such as permanent motor weakness and sensory loss in the lower extremities. Herein, we describe a case of SIH following spinal anesthesia. The patient was a 30-year-old man who underwent treatment for accessory navicular syndrome at our department. The patient was not receiving anticoagulation therapy, and spinal anesthesia was thus selected. No symptoms of hematoma were observed in the immediate postoperative period, but the patient complained of pain in both buttocks on postoperative day 5. However, neither motor weakness nor sensory loss were observed. Additionally, as the radiating pain extending to the lower extremities typical of neurological pain was not observed, musculoskeletal pain was suspected. Magnetic resonance imaging revealed intradural hematomas at L4-5 and S1. Conservative treatment and follow-up evaluations were performed to ensure that additional neurological sequelae did not occur. Six months after symptom onset, his pain Numeric Rating Scale score was 0, and no other neurological findings were observed. However, in patients who undergo spinal anesthesia, localized pain in the back without other neurological symptoms and lack of radiating pain may be associated with more than musculoskeletal pain. Such patients must be continuously monitored. Spinal intradural  hematoma (SIH) is caused by lumbar spinal punctures, underlying neoplasm, old age, infection, spinal surgery, anticoagulation therapy, and bleeding disorders  ,2,3,4. NThis study was approved by the Institutional Review Board (IRB No. 2022-02-009), and consent was obtained from the patient for the publication of this report.2, 1500 to 2000 times/region, 7 Hz) was provided; however, the symptoms were only temporarily improved and later worsened again. The patient complained of pain in the bilateral sacrum, and a Patrick’s test was conducted. Although the result was negative, a joint injection was conducted on both sides to evaluate inflammation of the sacroiliac joint [This case was a 30-year-old male patient who works as a motorcycle deliveryman. His body mass index in the historical record was 26.7, and he had no specific medical history or drug use, except that he had stage 1 obesity. He injured himself by falling while walking on the street, and the subsequent pain persisted to the extent that it interfered with walking, with pain on the inside of the foot, and the patient visited the hospital. On radiological findings, an accessory bone was found in the navicular bone , so the ac joint . HoweverAfter MRI, a conventional conservative treatment and continuous physical examination were provided to ensure that additional neurological sequelae did not occur. As no serious complications such as motor weakness, sensory loss, urinary distension, or any neurological sequelae were observed and the pain was relieved, it was decided to monitor the patient’s progress with follow-ups periodically after discharge. Three months after discharge, contrast-enhanced MR images were obtained to determine the cause of the hematoma and assess the improvement of the condition. MRI revealed that the intradural hematoma at L4-5 had decreased in size and that the nerves were displaced to the left side. There were no findings of tumor or vascular malformation .Six months after symptom onset, the pain Numeric Rating Scale (NRS) score was 0, and no other neurological findings were observed (Although the patient showed findings indicative of SIH and pain in the bilateral sacrum, paralysis of the lower extremities or serious neurological findings such as sphincter dysfunction were not observed. His symptoms improved over time. In patients who develop SIH after spinal anesthesia, the symptoms generally manifest 3–4 days later . In the In spinal hematoma, although blood does not press on the nerves, it may have neurotoxic effects on the spinal cord , causingSIH is caused by various factors; however, the pathogenesis of hematoma has not been clearly established ,11. AddiIn other reported cases of SIH at the lumbar level , hematomas were observed after spinal anesthesia in patients without any relevant medical history, as in our case ,13. MoreIn one unique case, it was reported that bleeding of a cranial hematoma may have descended toward the spine following gravity, and that this may have caused a spinal hematoma. Therefore, it was recommended that brain imaging also be conducted if the patient complained of a headache  As in thA total of 33 previous cases of spinal hematoma have been reported between 1911 and 1981. Eleven patients had underlying diseases and died, and nine patients achieved complete neurological recovery, indicating that the prognosis of spinal hematoma is generally poor . HoweverIn cases in which it was difficult to determine the definite cause, it is possible that the rapid increase in abdominal pressure of the large radiculomedullary vessels and abundant capillary network in the subarachnoid space may rupture and form a hematoma, spreading to the subdural space ,18. OtheIn patients who exhibit hematoma-induced neuropathy symptoms and do not undergo surgery, there is a 63.6% possibility of developing serious sequelae such as permanent paralysis of the lower extremities and sphincter dysfunction. However, in those who undergo emergency surgery immediately after symptom onset, the risk of serious sequelae is significantly lower, at 17.9% . TherefoHowever, when a patient who is taking anticoagulants or suffering from coagulopathy develops hematoma due to spinal anesthesia, and a decompression surgery is urgently performed on the spine, difficulties in bleeding control due to surgery and intraoperative bleeding may further compress the spinal cord, leading to additional damage . TherefoWhen there are no serious neurological complications caused by SIH, conservative treatment is commonly provided. Provided complications such as motor weakness are absent, conservative treatment is associated with a good prognosis of pain symptom recovery within a few hours at the earliest . In the In this report, a young patient with no underlying disease who was not receiving anticoagulant therapy developed SIH after spinal anesthesia. Although patients may not be considered to be at high risk of spinal hematoma, the possibility of a hematoma must be carefully monitored after surgery. Furthermore, in patients who undergo spinal anesthesia, localized pain in the back without other neurological symptoms and lack of radiating pain from the lumbar level may be associated with more than simple musculoskeletal pain. Such patients must be continuously monitored for potentially lethal or permanent neurological complications and undergo MRI for an accurate diagnosis.


P < 0.01). This led us to conclude that acupuncture has pain relieving effects against pain caused by aromatase inhibitors.Although acupuncture has been used in clinical practice for thousands of years, it remains a controversial treatment option to help alleviate pain in cancer patients. In this study, we analyzed published material on randomized trials of acupuncture from MEDLINE published up until July 31, 2018, to assess its effects on pain experienced by cancer patients. Revman 5.0 software was used to conduct meta-analysis with pain score as the index. The results of nine randomized controlled trials involving 592 patients were analyzed and showed that acupuncture can relieve the pain caused by aromatase inhibitors. Weighted mean difference of worst pain and pain severity was -3.03, 95% CI  and -2.69, 95% CI , respectively ( Aromatase inhibitors are used in the treatment of breast cancer . HoweverAcupuncture is an ancient traditional Chinese medicine therapy practice, whereby needles are inserted at certain anatomical points in the body to alleviate specific symptoms. Acupuncture also involves the use of techniques such as twisting and lifting of the needle to stimulate specific parts of the human body to treat diseases , 6.However, acupuncture is a controversial therapy for the chronic pain, as it cannot be proven by biomedicine. Traditional acupuncture theory is not based on anatomical structures but rather landmarks such as meridians and nonphysiological processes. Therefore, it was reported that acupuncture has short-term physiological effects, but there is no information explaining what these effects are and the impact on the patients' therapy. Due to the lack of data, many clinical practitioners do not accept this concept as a treatment option.In this study, we perform a data meta-analysis of high-quality trials of acupuncture for the therapy of the pain caused by aromatase inhibitors. These results could be used as evidence for acupuncture's ability to relieve pain caused by aromatase inhibitors.The protocol of the analysis was as follows: literature that was published from 2007 to 2018 was selected. Studies were considered eligible for this present study if they met the following conditions: (1) the patients had been on aromatase inhibitor treatment and received acupuncture needling therapy; (2) the patients received either sham acupuncture or no acupuncture (control group); (3) the primary endpoint was measured more than 4 weeks after the therapy of acupuncture; (4) all of the patients were randomly divided into groups. Cases were selected for our meta-analysis if they met the following conditions: (1) that the patient had received aromatase inhibitor therapy for the treatment of breast cancer. (2) The patient was willing to receive acupuncture treatment for treatment of pain associated with the use of aromatase inhibitors. The patients were then randomly divided into two groups. One of the groups would receive acupuncture needling therapy, and the other group would be subjected to placebo treatment. The patients were then assessed 4 weeks after acupuncture therapy, and results were recorded.The results for each study were analyzed by the authors of this manuscript. The effect size was entered into a meta-analysis program using the RavMan (version5.0) software. Both fixed effects and random effects were evaluated.χ2 test which was used to analyze the heterogeneity of the study, and the standard was α = 0.05; when the P value > 0.05, it indicates that the quality of each study is homogeneous, and the fixed effect model was selected; otherwise, random effects model was selected. Odds ratio was used for counting data and the measured data was expressed by weighted mean difference. Both of them were based on 95% confidence interval as the effect comprehensive scale.RavMan (version5.0) software was used for meta-analysis. Adopt first According to the search and data collection methods, nine studies met the inclusion criteria, which included a total of 592 patients . The ninχ2 = 5.32, P > 0.05, indicating no statistical heterogeneity. The results of fixed effect model showed that the difference between the groups before and after acupuncture was statistically significant (P < 0.01), indicating that acupuncture had a better inhibitory effect on relieving the pain caused by aromatase inhibitor.Evaluation of analgesic effect: nine studies show P < 0.01).To further determine the effects of acupuncture, the pain scores that were recorded before and after the therapy were evaluated by using the following indicators: worst pain, WOMAC-pain, and pain severity. The results showed that there was statistical heterogeneity in the scores before and after the therapy of acupuncture. Weighted mean difference of worst pain and pain severity is -3.03, 95% CI -3.90,-2.16) and -2.69, 95% CI , respectively (Figures 6 and -2.Antifatigue effect and influence on mood improvement: research showed that acupuncture can also improve fatigue symptom of patients. After 6 weeks of acupuncture, fatigue decreased significantly in patients. Acupuncture also had a greater impact on patients' emotions. After treatment, patients' mood showed some improvement.Based on the meta-analysis, results showed that acupuncture could improve the quality of life of breast cancer patients after the treatment by using aromatase inhibitors.β-endorphin, enkephalin, and dynorphin; the last part is the molecular mechanism, such as electroacupuncture can regulate the release of TNF-α, interleukin-1β, interleukin-6, and prostaglandin-E2. They could immediate the long-term analgesia. The quality of research methodology and nonstandard reporting could affect the quality of clinical research [At present, the mechanism of acupuncture anesthesia and analgesia has been explored , 17. Theresearch , 19. We research . There a


The purpose of this study was to investigate the differences in the therapeutic effectiveness of CT-assisted infiltration of a local anesthetic + corticosteroid between nerve root and facet joint capsule in patients with chronic complaints. In this prospective trial with a 12-month follow-up, a total of 250 patients with chronic low back pain and radiculopathy were assigned to two groups. In the first group, patients with specific lumbar pain due to spondyloarthritis received periarticular facet joint capsule infiltration (FJI). In the second group, patients with monoradicular pain received periradicular infiltration (PRI) via an extraforaminal selective nerve block. Clinical improvement after FJI and PRI regarding pain (NRS), function (ODI), satisfaction (McNab), and health related quality of life (SF-36) were compared. Minimally clinically important difference (MCID) served as the threshold for therapeutic effectiveness evaluation. A total of 196 patients were available for final analysis. With respect to the pain reduction and functional improvement , the PRI group performed significantly better (ptreatment < 0.001) and longer over time (ptreatment × time 0.001) than the FJI group. Regarding pain and function, only PRI demonstrated a durable improvement larger than MCID. A significant and durable therapeutic value was found only after receiving PRI but not after FJI in patients with chronic pain. Degenerative changes in the lumbar spine are a common cause of chronic pain, physical limitations, reduced health-related quality of life, and absenteeism. As a consequence, these changes are associated with considerable social and health costs in Western societies ,2,3,4,5.Facet joint degeneration, a real joint-segment-joint degeneration, is often a trigger of back pain. In addition, disc herniation, recess, or neuroforaminal stenosis often affects the nerve root and can lead to leg pain ,7. A varLocal anesthetics and steroids are often used here. Local anesthetics have been postulated to provide relief by various mechanisms, i.e., suppression of nociceptive discharge, the block of the sympathetic reflex arc, the blockade of the axonal transport, and anti-inflammatory effects . SteroidHowever, based on current research, the duration of the effect of therapeutically intended infiltration as it relates to the treated tissue, nerve root, or facet joint, particularly in the case of chronic and specific complaints, remains unclear. In previous studies, infiltration locations were considered partially together and partially individually compared with placebo groups, and the temporal aspect of complaint duration was insufficient . HoweverA total of 250 patients were screened in a single-center , prospective, nonrandomized, and nonblinded study between June 2018 and December 2019. Patients were included in the event of their consent approval. The number of cases was calculated based on the statistical parameters of the clinical outcome scores of a test cohort. The effect size for the power analysis based on a 2-sided, 2-way ANOVA with 4 or 5 measurement repetitions, and was thus set to 0.12. With a ß of 0.2 and an α of 0.05, the required group size was determined to be 86 patients. Assuming a rather conservative calculated dropout rate in telephone interviews of 45% after one year, the total group size was approximately 125 patients per group. The presented study was registered with the Trial Registry Number: DRKS00023722 .Study approval was obtained from the ethics committee of the University Hospital Jena, Germany (No. 5487-3/18) and all methods were performed in accordance with the relevant guidelines and regulations. All patients were informed about the study preinterventionally and gave their written informed consent to participate in the study.The inclusion criteria were patients aged ≥ 18 years with predominantly low back pain or predominantly monoradicular leg pain after the failure of structured noninvasive conservative treatment with pain relievers and physiotherapy for at least six weeks and a complaint duration of at least 12 weeks. This includes exercise, paracetamol or Nonsteroidal Anti-inflammatory Drugs, manual therapy, acupuncture, and spinal manipulation in patients with radiculopathy. PRI was performed in patients with predominantly unilateral lumbar radiculopathy based on single-level nerve root compression  confirmed by morphological imaging (MRI or CT). FJI was performed in patients with predominantly specific lumbar pain due to single-level lumbar segment degeneration  confirmed by morphological imaging (MRI or CT) . The defThe exclusion criteria included previous surgeries on the affected spine segment, multilevel pathologies in the MRI of the lumbar spine, and bilateral radicular complaints. Furthermore, patients in whom the peri-interventional risk profile was increased due to other diseases were excluded. These diseases included insufficiently controlled diabetes mellitus, intake of oral anticoagulants, clotting disorders, increased laboratory infection parameters  were also excluded from the study. In addition, patients who could not meet the requirements for telephone interviews and patients with a known allergy to local anesthetics (LA) or corticosteroids were excluded from the study. Patients were consecutively assigned into two groups depending on the site of infiltration. Patients with lumbar pain due to facet joint arthrosis received FJI (FJI group), whereas patients with radicular pain due to nerve root affection received a PRI (PRI group).All patients were placed prone on the table for the computer tomography scanner  and treated under sterile conditions. All interventions were standardized by a single doctor (CL). Pre-interventional oral drug sedation of the patient was performed as needed.®®, MIBE GmbH Arzneimittel; Lidocaine hydrochloride) + 0.5 mL corticosteroid  or only 2 mL LA in cases of steroid allergy/intolerance. No contrast agent was used in either group due to CT-secured needle positioning. Before injection, needle aspiration was performed to prevent vascular spread.During FJI treatment, the needles were positioned  after appropriate CT-based identification. As intra-articular injection is often not possible due to advanced degeneration of the facet joints, the needles were placed directly around the affected facet joint capsules , were recorded. In addition, grades of facet joint arthritis were determined in the FJI group using the Fujiwara classification system. In the PRI group, MR morphological differentiation of nerve root compression into moderate and advanced was performed .The patient’s overall pain perception was assessed using a numerical rating scale . Leg pain (NRSleg) and back pain (NRSback) were also assessed in isolation using the same numerical rating scale. The Oswestry Disability Index (ODI) was used to assess functional restriction . The HeaPain and function  were assessed preprocedure and by telephone (except on day one with only NRS score) at the follow-up appointments at 6 weeks and at 3, 6, and 12 months. The SF-36 form was collected preprocedure and queried postprocedure for the 12-month follow-up.Epidemiological data and patient scores were compared between the groups. To assess the therapeutic value of PRI and FJI, the improvements in the overall pain scale and the ODI compared to the preinterventional value  were compared to the minimal clinically important difference (MCID) for chronic complaints. According to previous work, the MCID was established for pain deltaNRSoverall = 2. For function, the deltaODI = 16% ,22,23,24The statistical evaluation of this work was performed using SPSS Statistics .t-test for independent samples, and the normal distribution of the data was assessed in advance using the Kolmogorov–Smirnov test. Categorical data were evaluated using Fisher’s exact test, and continuous data were evaluated using Student’s t-test. Given that the primary and secondary target values were measured at 5 or 6 points in time, the scores were subjected to a 2-way ANOVA for repeated measures using post hoc Bonferroni tests. The Greenhouse–Geisser correction was used to assess the sphericity. A double-sided significance check was performed for all tests, and a p-value < 0.05 was assumed to indicate statistical significance for all statistical tests.The demographic data were assessed using Student’s p = 0.151).A total of 196 patients were available for data analysis . The patAll clinical scores  were significantly improved over time (ptime < 0.001). With respect to the ODI, NRSoverall, and NRSback, the PRI group performed significantly better (ptreatment < 0.001) and longer over time (ptreatment × time 0.001) than the FJI group. Additionally, leg pain was significantly different between the two groups over time . For detailed results and post hoc tests, see p = 0.033) after the intervention, whereas the PRI group showed a significant improvement in pcs (p < 0.05). This resulted in a significant difference in pcs between the two groups after 12 months  with patients in the PRI group having a higher baseline value. Although no significant change in the baseline value was noted 12 months after the intervention in patients in the PRI group, significant deterioration in patients in the FJI group was noted .Baseline mcs values were significantly different between the two groups  reported slightly transient and self-limiting side effects (1–4 h). These effects included initially increased low back pain (eight patients); numbness in the leg (ten patients); headache (seven patients); mild allergy, including redness of the face (three patients); and heartburn (one patient). Due to the self-limiting course of the side effects, no additional drug administration was necessary that could affect the outcome of the infiltration therapy. No serious adverse events were reported during the 12-month observation period.To the best of our knowledge, this study is the first to prospectively assess a direct comparison of the therapeutic value of infiltration therapies (FJI vs. PRI) in chronic complaints, under everyday clinical conditions. The study demonstrated that PRI showed a durable therapeutic effectiveness compared to FJI. Although a clinically meaningful pain reduction in back pain and possibly leg pain (MCID: NRS) was no longer detectable beyond three months after FJI, patients who received a PRI reported a clinically significant reduction in leg pain (LEP) and (if present) low back pain (LBP) over the entire period of the follow-up. The same applies to pain-associated disability in everyday life (MCID: ODI). Significant improvement in the physical health-related quality of life (SF-36: pcs) was noted in both groups, but patients who received a PRI benefited significantly more from infiltration therapy. The present results also reflect higher patient satisfaction in the PRI group.The study demonstrates the dependence of the effectiveness of structural infiltration with local anesthetics and steroids. While a chronic neural affection seems to respond very well to the local application of the medication, arthrosis of the facet joints can only be affected to a limited extent by local therapy. The slight effect on arthritically altered joints does not seem surprising as this was also observed in other joints, such as the knee or hip joint ,26. The Clinically meaningful short- and long-term pain reduction after a PRI was demonstrated in other studies, which investigated the outcome of nerve root infiltration with radicular symptoms . The autThe presented study is not without limitations. First, a steroid was not applied to all patients, so the local drug composition was not completely uniform. However, the vast majority had steroid infiltrate. Based on the study design, effects attributed to the steroid versus the local anesthetic drug remain unclear. In this regard, individual studies show no major differences between local anesthetics and an LA/steroid mixture . Second,Ultimately, there are also different infiltration techniques for the pathologies described . Therefore, only conclusions about the techniques used can be drawn from the present study. Alternative forms of administration and application could show different durations. Thus, different effects could be observed depending on the approach used, which subsequently limits the comparability of the present work with other outcome studies that use alternative infiltration techniques.We demonstrated that chronic back or leg pain, even when performed within a standardized setting, does not always respond equivalently to lumbar spinal needle intervention. Rather, the underlying pathology (facet joint arthritis vs. radiculopathy) seems to play a crucial role regarding therapeutic efficacy.Based on the available results, CT-based PRI represents a suitable and easy method to provide long-acting therapy to patients with chronic radicular pain and associated LBP. Additionally, based on our study’s clinical results, infiltration of facet joints holds no notably durable therapeutic value and may be used as a diagnostic tool only to secure the potential cause of the complaint. Alternative forms of therapy, such as facet joint radiofrequency denervation, surgical procedures, and multimodal concepts, should be considered in this regard.


Background: In neck pain treatment, many therapies are focused on etiology, while it is well-known that placebo analgesia is also present in these therapies. The specific efficacy for etiology may be underestimated by ignoring their actual placebo effect. In this study, a logistic regression analysis is used to explore the risk factors causing different placebo responses in patients with neck pain among two RCTs. The probability of the placebo effect is predicted based on these risk factors.Methods: Trial A and Trial B were similarly designed, randomized, double-/single-blind, placebo-controlled trials in patients treating neck pain with Qishe pill or Shi-style manipulation. Both studies set a placebo pill twice a day or traction for every other day as control. For further analyses on the placebo effect in neck pain management, logistic regression was used to assess subgroup-placebo interactions. The odds ratio assessed a significant influence on the placebo effect.Results: In this pooled analysis, the total number of patients recruited for these two studies was 284, of which 162 patients received placebo treatment (placebo drug or traction for every other day). No statistically significant differences are found at baseline between the participants with placebo effect and non-placebo effect in the gender, age, and disease duration except in VAS and NDI at the initial time. There are numerically more patients with placebo effect in the shorter disease duration subgroup (< 4 months [76%]), higher initial VAS subgroup (>60 mm [90%]), and worse initial NDI subgroup (>24 [72%]) compared with the gender and age subgroup. An ROC curve is established to assess the model-data fit, which shows an area under the curve of 0.755 and a 95% confidence interval of 0.677–0.830. Participants who show placebo effect after 2 weeks have significantly lower VAS scores after 4 weeks, while there is no significant difference in NDI improvement between the two groups after 4 weeks.Conclusion: Neck pain patients with shorter disease duration are more likely to overscore their pain severity, because of their less experience in pain perception, tolerance, and analgesia expectation. Neck pain is known as pain in the neck with or without upper limb disorders, which may last for several days . Neck paIn neck pain treatment, many therapies are more focused on etiology, such as nerve root compression, muscle spasm, inflammation, and so on, while it is well-known that placebo analgesia also induces discrete physiological changes mediated by the endogenous opioids system, which is called as placebo effect , but itsRegarding therapies such as placebo, there are various forms such as sugar pills, saliva injection, or sham surgeries , which aRCTs for pain treatment are commonly used placebo to identify the specific efficacy of the placebo effect, in which all the settings, providers, and subjects’ baseline are designed with the same and homogenous conditions to ensure comparable as possible . HoweverOur research team has conducted two randomized placebo-controlled trials on neck pain. To further investigate the analgesic effect of the placebo treatment itself, we combined all the participants’ data in the respective placebo treatment group of these two RCTs for a pooled analysis. Patients receiving placebo treatment were divided into two groups according to self-reported pain relief after 2 weeks. We hypothesized that considerable pain relief in the placebo treatment group may exist placebo effect. Therefore, in this study, a logistic regression analysis was used to explore the risk factors causing different placebo responses in patients with neck pain among two retrospective, blind, placebo-control RCTs. The probability of the placebo effect was predicted based on the risk factors.Detailed design and clinical results of Trial A and Trial B have been reported .Trial A and Trial B shared many study design elements, allowing for integrated analyses. Briefly, both trials were randomized, blind, placebo-controlled, Phase 2 studies. These studies were conducted in accordance with the principles of the Declaration of Helsinki. The institutional review board or independent ethics committee at each site approved the protocols, and all patients provided written informed consent. All authors had access to the study data and have reviewed and approved the final manuscript.Trial A and Trial B were conducted in patients diagnosed with cervical spondylotic radiculopathy (CSR), with the primary objective of evaluating the efficacy of Qishe pill  or Shi-style manipulation  versus placebo  or traction  as measured by the proportion of patients who became neck pain-free and most neck-related hypofunction at 4 weeks. The placebo and active treatment arms received either the same strength of Qishe pill/shi-style manipulation or placebo/traction (1:1 ratio).All participants were selected from the general outpatient clinic in the five hospitals across China , where the patients will be diagnosed with cervical radiculopathy confirmed by a neurologist, and then diagnosed based upon clinical symptoms, physical examination on nerve signs, and imaging .Inclusion criteria are age between 18 and 65 years, pain or stiffness in the neck for at least 2 weeks, neck symptoms reproducible during physical examination, and neck pain on neck disability index (NDI) of 18 or more. Further inclusion prerequisites are willingness for treatment and to adhere to measurement regimens, no involvement in litigation, and written informed consent. Excluded criteria are patients whose history, signs, and symptoms suggested a potential non-benign cause (including previous neck surgery) or evidence of a specific pathologic condition.At randomization, patients will be assigned to receive Qishe pills (or matching placebo) at 3.75 g twice per day. In this study, the same outer packing will be used for both the Qishe pill and the matching placebo. Therefore, the treating physicians, participants, and investigators will be blinded to treatment assignment.In Trial A, the placebo is composed of β-cyclodextrin, colorants, and food flavoring, to look and taste similar to the Qishe pill, which is a thin 0.15 g film-coated pill with a slight odor and bitter taste. The Qishe pill and matching placebo used in the trial are both manufactured and provided by a pharmaceutical company that meets the requirements of Good Manufacturing Practice. All significant medicine information, including ingredient composition, heavy metals, etc., are provided by the same company.In Trial B, patients in the traction treatment group received intermittent cervical traction (ICT) for 20 min, every other day for 4 weeks. A previous Cochrane systematic review reported that mechanical traction presents little effect on neck pain, while it is still believed to be clinically effective . As a reThe primary study outcome is pain severity . Secondary outcomes are a composite of functional status (measured by NDI), patient satisfaction, and adverse events as reported in the trial. The visual analog scale measures the amount of pain, which is a pain score ranging from 0 (no pain) to 100 mm (very severe pain) .Operationally, the VAS score is displayed as a horizontal line, 100 mm in length, with word descriptors anchored at each end. The patient marks on the line the point that they feel represents their perception of their current pain. The VAS score is then determined by measuring in millimeters from the left end of the line to the point that the patient marks. The VAS score and NDI will be measured at all the measurement points . Patients were not shown their previous scores when they went for the current assessment.p-value was calculated for placebo-by-subgroup interaction, based on logistic regression with terms for study, subgroup, and placebo-by-subgroup in the model. The odds ratio assessed a significant influence on the placebo effect. The odds ratio (OR) and the flag of p-value > 0.05 Hosmer and Lemeshow test for homogeneity of OR are displayed. ORs were created with the probability of the active placebo effect as the numerator and the actual incidence of the active placebo effect as the denominator.Data handling rules and full analysis methods were previously described in To detect patients who are easy to respond to placebo therapies, a predictive model was constructed based on the multivariable logistic regression coefficients. The predictive performance of the model was quantified with the area under the receiver operating characteristic curve (AUC), which ranges from 0.5 to 1.0 for sensible models. The internal validity of the model was assessed by bootstrapping techniques . Model pp-values less than 0.05 are referred to as having statistical significance for a factor difference unless otherwise noted. However, p-values should not be overinterpreted for covariate analyses.Tests with 2-sided The total number of patients recruited for these two studies was 284. The details on patient recruitment, follow-up, and selection during the posthoc analysis are summarized in Demographics of the patients at baseline are described in p > 0.05), age (p > 0.05) and disease duration (p > 0.05) except in VAS and NDI at the initial time (p < 0.05).No statistically significant differences were found at baseline between the participates with active placebo effect and non-placebo effect in the gender , and ICT for the control of Shi-style manipulation . Both interventions have been identified as placebo treatments in previous studies .In these two RCTs for neck pain, we found that some patients with short disease duration may overscore their pain severity, who may also report a large improvement in pain and function, even in the placebo group. Extracted and re-divided into two groups based on whether there was a substantial improvement in pain after 2 weeks to define whether there was a “placebo effect”, using the subjects’ baseline information as a potential risk factor, a logistic regression analysis was used to explore the risk factors causing different placebo response, and probability of placebo effect was predicted based on these risk factors.This study presented a reasonable and objective method to quantify and evaluate the perception and the expectation in placebo therapy, which showed that pain severity and disease duration are the two most important factors in placebo responses. Neck pain patients with shorter disease duration may be hard to describe their perception of pain, which may probably overscore in their first self-report and easily decrease the pain score after a 2-week placebo treatment with their expectations. On this basis, in the recruitment process, it is necessary to exclude neck pain patients with shorter disease duration, who present extremely high self-reported pain. If patients have finished all the treatment and follow-ups, in the statistic process, some weighted conversion from the probability of placebo response may take place of a simple “A-B” efficacy difference between two groups.These results on the probability of placebo effect interpreted effect on different pain perception, tolerance, and expectation, which may be related to individual emotion status and disease duration. Patients’ perceptions of the treatment may directly influence the outcome, which may be influenced by treatment description  and verbOur study has limitations, first, the participants we investigated are only patients with neck pain; second, the sample size is moderate to conduct this analysis. Despite the limitations, these studies provide insight into the potential placebo effect in patients with neck pain. In order to verify the accuracy of placebo effect detection, a more accurate objective measurement of pain and its related brain functional MRI will be used for further investigation, which may reveal specific processes of analgesia  with accurate evidence . Also, fIn summary, a logistic regression analysis has shown that disease duration of neck pain is the most risk to present an excessive placebo effect in management. Neck pain patients with shorter disease duration are more likely to overscore their pain severity, because of their less experience in pain perception, tolerance, and analgesia expectation.