To assess the efficacy of intercostal nerve protection by intercostal muscle (ICM) flap in post-thoracotomy pain improvement compared to intracostal suturing.nd week, 1st, 2nd, 4th and 6th months after thoracotomy.In a randomized controlled trial, ninety-four patients undergoing posterolateral thoracotomy surgery were divided into two subgroups. Intracostal sutures in isolation and in combination with ICM flap techniques were used for thoracotomy closure in both groups. Numeric Pain Scale and Visual Pain Scale as pain scores were assessed on the first, second, third, fourth, fifth, sixth and seventh postoperative days and follow-up visits during the 2Out of 94 patients, 58 were male and 36 were females. While the mean age of patients in intracostal group was 45.3 ± 17.6 years, it was 47.4 ± 16.1 years in intracostal plus ICM flap group. The mean operation time for the first group was 191.0 ± 74.7 minutes, while it was 219.3 ± 68.8 minutes in the second (p>0.05). Numeric rating score and visual pain scale did not demonstrate any significant difference in pain severity on postoperative days and follow-up visits between both groups (p>0.05). Although the trend of pain reduction was significant in each group (p<0.001), the difference was not statistically significant (p>0.001).Intracostal sutures in combination with muscle flap did not reduce postoperative pain in thoracotomy compared with intracostal sutures alone in thoracotomy closure. Posterolateral thoracotomy is a widely performed procedure accompanied with post-operative pain and numerous studies have suggested intraoperative factors to influence the prevalence of this complication.9Despite several studies, chronic pain after thoracotomy is still causing significant problems influencing postoperative life quality of patients. Although, there are some powerful meta-analysis and controlled trials,After obtaining informed consent all patients admitted for posterolateral thoracotomy in cardiothoracic department of Tabriz Imam Reza Hospital from March 2012 to March 2015, were enrolled for this study. (IRCT NO: 2015122216077N4) The exclusion criteria were: presence of any pain before surgery, long-term use of non-steroidal anti-inflammatory drugs (NSAIDs) or analgesics, narcotic addiction, psychiatric disease, radiologic evidence of invasion to parietal pleura or rib, age lower than 19, history of receiving corticosteroid in last six months, preoperative chemotherapy or radiotherapy, neuropathy, previous thoracotomy, epidural catheter dysfunction, incision infection or empyema, loss of consciousness after surgery or need for mechanical ventilation after surgery, re-operation due to hemorrhage or other thoracic emergencies and patients discharging with chest tube or Heimlich valve.Using a computer generated randomization provided by a statistician, a surgery resident, not participating in the study, assigned all patients randomly to either the intracostal suture (ICS) group or the intercostal muscle flap and intracostal sutures (ICM) group. A thoracic epidural catheter was placed before the operation. A standard posterolateral thoracotomy with division of the latissimus dorsi muscle and preservation of the serratus anterior muscle was performed by the same surgeon. The pleural space was entered through the fifth or the sixth intercostal space. The cautery was used to open the intercostal space over the upper border of the lower rib.In the ICM group, a 10 cm to 15 cm segment of the intercostal muscle underneath the upper rib was partially dangled by low energy electrocautery. The chest retractor was put behind the intercostal muscle to avoid crushing it between the lower border of the rib and the upper blade of the retractor. To avoid rib fracture, we attempted to use a piece of gauze between the blade and the rib and slowly opened the chest retractor. When the procedure was completed, patients had one or two 28F soft chest tubes placed.For closure, three or four intracostal sutures were passed through predrilled holes on the lower rib and passed over the top of the upper rib, according to Cerfolio et al.st, 2nd, 4th and 6th months later  and visual pain scale (VPS). In NRS, zero score means no pain and 10 score means the most severe pain that patients experience. Visual pain score is shown with even digits ranging from 0-10 and is determined by using some standard. Pain evaluation was done in days: 1, 2, 3, 4, 5, 6, and 7 of the hospitalization. After patients’ discharge, the pain evaluation scores were recorded during interviews at post-operative second week and the 1hs later . All memAll collected data was analyzed with SPSS 22. Descriptive statistical methods , chi-square test, independent and paired sample t-test and ANOVA with repeated measures were used to analyze the data. The p value for differences was considered less than 0.05.During a 3-year period, out of 112 patients who received posterolateral thoracotomy for various reasons, 96 patients were eligible to participate in the study . No statth intercostal incisions, 10 patients had 6th and 4 patients had 7th intercostal incisions to access the thoracic cavity. In ICM group, 4 patients had 4th intercostal incisions, 40 patients had 5th and 3 patients had 7th intercostal incisions. The differences were not statistically significant (p>0.05).The mean duration for flap preparation in ICM group was 4.5±1.7 minutes. The mean duration of hospitalization for ICS group was 7.0±2.0 days and for group B was 8.9±6.1 days (p>0.05). In ICS group, 33 patients had 5P> 0.05).The closure of ICS group in three patients was with two sutures and in 44 patients with three sutures. In ICM group, the closure was with two sutures for five patients and with three sutures for 42 patients. There was no statistically significant difference between them (P: 0.401). In addition, none of the patients had needed second chest tube, postoperatively.Nine patients and eleven patients had one chest tube in ICS group and ICM group, respectively which had not significant difference between two groups (P: 0.753); in order to prevent rib fracture effect on patients’ postoperative pain, both patients were excluded from study group.Regarding intraoperative actions, surgeon tried to reduce rib fracture as much as possible. However, one patient (2.1%) in ICS group and ICM group had one rib fracture. Although, no significant difference was observed between groups in terms of rib fracture (P: 0.121). Statistical analysis using chi-square test showed, significant difference observed in terms of atelectasis incidence between groups (P: 0.029), Use of epidural catheter, intercostal block and analgesic were obligatory for all patients. Analgesic protocol was based on intravenous paracetamol and morphin. Collected NRS scores and visual scores were regrouped into two time periods, namely as early post-operative pain from day 1 to day 7 and late pain including 2nd week, 1st, 2nd, 4th and 6 months after thoracotomy , following by atelectasis in 7 patients (six patients in ICS group and one patient in ICM group).  in both groups. However, the decreasing trend between these two groups was not statistically significant (p>0.001).Results of the current randomized controlled trial revealed that muscle flap preparation was not significantly effective in post thoracotomy pain improvement, and post-operative pain in intracostal thoracotomy closure was similar to combination of intracostal and ICM flap technique.Neuropathic pain accounts for most of the post thoracotomy pains.14Different methods are being used for intercostal nerve preservation. Generally, intracostal methods are preferred in comparison to pericostal methods.16The efficacy of using intercostal muscle flap in diminishing pain is still controversial.Potential invisible damage to the intercostal nerve while raising a muscle flap might be a major concern. It seems that pain could be affected by other factors such as the patients’ psychological status and subjectivity of pain sensitivity. The force of retraction and a broad width of entry space may contribute to the intercostal nerve injury. A narrow width of entry space, short operation time and releasing the retractor periodically would be helpful for pain relief.Although, early and late post thoracotomy pain is a common condition with high neuropathic region, there was no significant difference in the pain management between two approaches used in the current study. Therefore, more clinical trials with larger population group are suggested for further studies. In addition, comparison of posterolateral and anterolateral should be taken into consideration in future studies.Our study had some limitations. Due to small number of cases referred to our hospital, the study group was small. Hence there is a need for studies with larger population. Secondly, due to lack of patients’ cooperation, we were unable to prolong our follow up period.Thoracotomy closure with a combination of intracostal sutures and intercostal muscle flap method have more accurate intercostal nerve preservation, has no significant advantage compared with simple intra costal sutures in post thoracotomy pain management.


Chronic scrotal pain (CSP) is a common and well recognized symptom of young males presenting to primary care units. Historically, CSP is defined as a testicular pain lasting for over 3 months. However, its etiology and outcome are poorly understood and its management is largely empirical. This study was conducted to examine the frequency, spectrum of pathology and outcome of CSP among young adults.The medical records of 382,036 young males were reviewed for anamnestic information, physical findings, primary care physician decisions, and final outcome. CSP, defined as scrotal pain longer than 14 days, was recorded in 3084 patients (0.8%). The total number of primary physician’s visits due to this complaint was 16,222, with a mean of 5.3 visits per patient (range 1–37). Varicocele was the most common physical finding (54.1%). Other common findings were inguinal hernia (4.5%), genital infection (4.3%), hydrocele (4.2%) and referred pain (3.3%). 252 patients (8.2%) underwent surgical treatment but orchiectomy was not necessary in any patient. In 34.4% no specific etiology could be found. Neither malignant tumors nor testicular torsion were diagnosed in any patient.The prevalence of the diagnoses was similar between the different time groups—15–29 days, 30–59 days and more than 60 days. Considering the similar etiologies CSP over a wide spectrum of time we suggest defining CSP as testicular pain lasting longer than 14 days. Chronic scrotal pain (CSP) is a common and frustrating complaint that interferes with daily function of young men. It can lead to long evaluation process and its treatment is often ineffective –3.CSP is historically defined as an intermittent or constant testicular pain, unilateral or bilateral, lasting for over 3 months that interferes significantly with the patients daily activities . This CSThe management of CSP depends on the specific diagnosis or presumed etiology. Therefore, a thorough medical history, physical examination, laboratory tests (blood and urine investigations), imaging studies and specific tests like tumor markers and sexual transmitted disease screening, when indicated are crucial.The literature is poor in epidemiological data on CSP, its etiologies, prevalence and outcome. Data from questionnaires among urologists in Switzerland revealed a crude incidence of about 350–450 cases of CSP per 100,000 men between 25 and 85 years . Recent The aim of this study is to provide a comprehensive epidemiologic description of CSP using a large database and to challenge the current definition of CSP.At age 18, most healthy Israeli males begin three years of mandatory military service. Men diagnosed with significant chronic medical or mental illness are not drafted.Military recruitment can be delayed for a few years for high academic or religion studies. Soldiers who suffer from medical problem are treating by the general military clinic and being refer to a medical specialist as necessary. According to the Israeli military’s commands every medical visit is recorded in the medical corps database.The computerized medical corps database of all referrals to general practitioners from: January 2004 to December 2014 and the medical records were searched using the key words: pain, testis, varicocele and orchialgia. All patients in current study were treated initially by general practitioners and were referred to further evaluation as needed. Patients with testicular pain lasting longer than 2 weeks were included in the study. Patients with prior genital or hernia surgery were excluded.The patients were divided to three groups according to their symptoms duration: Group A—patients with symptom duration between 15 and 29 days, Group B—patients with symptom duration between 30 and 59 days, and Group C—patients with symptom duration above 60 days.The study was approved by the Israel army’s Institutional Review Board.Varicocele, hernia, hydrocele, skin lesion, torsion–detorsion and nephrolithiasis were diagnosed only after the approval of the physical examinations’ findings by ultrasonography. For statistical reasons, all genital tract infections were included together under one title of “genital infections”. Genital infections were diagnosed following positive urine or sperm culture or polymerase chain reaction (PCR) tests. The diagnoses of referred pain from the groins or adductor muscles were given after suitable findings in physical examination. The diagnoses of trauma to the scrotum were given upon patients’ report. Diagnosis of idiopathic scrotal pain was assigned when there were no clinical findings on physical examination, laboratory tests and ultrasonography.Statistical analysis was done using the Statistical Analysis System , with standard univariate analysis using unpaired t-tests for comparison of the means of groups. Various frequencies of diagnoses were compared with the Chi square or the Fisher exact tests. To determine the interdependence of univariate analysis, multiple logistic regression models of the variables that were significant on univariate analysis were used. Differences were considered statistically significant when the p value was less than 0.05.The medical records of 382,036 young males were reviewed, and 3084 patients (0.8%) with CSP were identified. 198 (6.4%) patients had symptom duration between 15 and 29 days (group A), 696 (22.6%) with symptom duration between 30 and 59 days (group B) and 2190 (71%) with symptom duration above 60 days (group C). Mean patient age was 19.24 years (range 18–27 years), mean weight was 67.6 kg and mean height was 174.8 cm.Data regarding primary physician visits and referrals for further evaluation is presented in Table Table The prevalence of the other diagnoses was similar between the different groups.Diagnosis of scrotal pain due to scrotal skin lesions, torsion–detorsion syndrome, scrotal trauma, scrotal tumors or nephrolithiasis were assigned in about 1% of patients or less. Malignancy and torsion of testis were assigned in none.CSP is common and frustrating complaint of young adults. In this research, a large database was surveyed and the authors had full access to the long term outcome of the cases, so the risk of missing important diagnoses is low. To the best of our knowledge, this is the first large scale survey of CSP in young men in a primary care setting. It was found that CSP affects 0.8% of the young men. The mean primary physician’s number of visits was 5.3 with one patient visiting the clinic 37 times. Referrals to specialist in Urology were also common and the mean number of referrals was 1.4 per patient (range 1–11).The etiologies of CSP in young men are reported in this study Table . VaricocAccording to Granitsiotis et al. nearly 25% of patients with chronic orchialgia have no obvious cause for the pain . In our The prevalence of the other diagnoses was quite similar between the different time groups from the shortest duration of pain (15–29 days—group A) to longest (more than 60 days—group C). This challenges the historic definition of CSP as pain lasting more than 90 days that is based on a study of 45 patients [Diagnosis of scrotal pain due to scrotal skin lesions, torsion–detorsion syndrome, scrotal trauma, scrotal tumor or nephrolithiasis were assigned in about 1% of patients or less, probably because these etiologies are of acute manifestation or because of the painless nature of these pathologies. A total of 252 (8.2%) patients underwent surgical interventions including: hernia surgery in 46 patients (1.5%) and varicocele and/or hydrocele repair in 206 patients (6.7%). The rates of varicocele and/or hydrocele surgery were higher in group C, probably because of failure of conservative treatments.The management of CSP depends on the cause or presumed etiology of the testicular pain. The key to successful assessment remains the history and physical examination and early use of ultrasound of testes and inguinal region is the most reliable imaging modality in the management of chronic testicular pain. Lau et al. observed that in patients with testicular pain longer than 14 days, sonography detected lesions in 28% of patients with no clinical findings on examination including varicocele, hydrocele, epididymal thickening and epididymal cyst . Thus, wTesticular torsion (TT) is a relatively rare urological emergency in which the diagnosis must be made accurately and rapidly to prevent loss of testicular function. TT is a medical situation of an acute presentation. However, TT may occur in patients with CSP. In current study, 25.9% of the patients visit at least once in the ED, in most cases because of physicians’ suspicious of TT. Yet TT and torsion of the appendix testes were not found in any of the patients and only 1.0% of the patients were hospitalized emergently for any reason.We report on the prevalence, etiologies and outcome of CSP in young men in a primary care clinic are reported. CSP affects almost 1% of the young males and can lead to repeated visits to the primary care clinic. Varicocele is found in half of the patients but significant pathology (tumor or torsion) are rare. Early use of ultrasonography is advised. It can rule out significant pathology, reassure the patient that the condition is benign and prevent revisits to the clinic. Considering the similar etiologies with minor variations of CSP over a wide spectrum of time (from pain longer than 2 weeks to pain longer than 60 days) we suggest defining CSP as intermittent or constant testicular pain lasting longer than 14 days that interferes significantly with the patient’s daily activities.First, our database is obtained from medical registries of the Israeli army and it may be difficult to generalize the finding of this study to the general population. This issue may have affected our results; however, military service in Israel is a compulsory and includes not only combat healthy soldiers but also non-active ones which their life style is similar to a civilian life. Another concern is the fact that the study was done retrospectively with no control group, further prospective studies in civilian population using this study findings are needed. The absence of validated questioners regarding quality of life makes it impossible to evaluate the real impact of CSP on quality of life.


One of the most common complications of root canal treatment is postoperative pain. The aim of the present clinical trial was to compare the severity of postoperative pain after root canal preparation with RaCe rotary system and hand K-Flexofile. n=48) based on root canal preparation technique. The teeth in both groups underwent one-session root canal treatment and the severity of postoperative pain was evaluated using visual analog scale (VAS) at 4-, 8-, 12-, 24- and 48-h and 1-week intervals. In addition, the type and dosage of analgesics were recorded. Data were analyzed with repeated-measures ANOVA. Statistical significance was set at 0.05. A total of 96 mandibular first and second molars were divided into two groups (P>0.05). There were no significant differences between the two groups in type and the number of analgesics in pain-free subjects . The difference between the two groups during this period and at subsequent intervals were not significant (There were no statistically significant differences in pain severity between the two groups at any intervals. Postoperative pain is a common complication in endodontic treatment with the occurrence of 1.4-16% . Age, geThere is some supportive evidence that one of the most important reasons for postoperative endodontic pain is the extrusion of infected debris from the root apex during chemomechanical debridement, which results in an acute inflammatory response . There aet al. [One of the most commonly used rotary systems is RaCe  system, which is mainly used with the crown-down technique. The design includes two grooves followed by one straight area without any grooves along the file, which appears to be an area for accumulation and evacuation of debris and can result in a decrease in screw-in effect in association with the use of the crown-down technique and enlargement of the coronal area of the root canal. This design increases the evacuation of debris from the coronal area of the root canal and decreases the extrusion of debris from the root apex, which might result in less severe postoperative pain -8. Foroget al.  showed sin vitro and postoperative pain under clinical circumstances. In this context, despite an increase in the extrusion of debris with the use of hand files compared to rotary files in various studies, in some studies no significant relationship has been found between them regarding the postoperative pain, which might indicate the role of other factors, in addition to the extrusion of debris, in the severity of postoperative pain [Several studies have shown that there is no clear-cut and significant relationship between extrusion of debris ive pain -12.Based on the results of previous studies -14, it aThis prospective randomized controlled clinical trial was approved by the Ethics Committee of Tabriz University of Medical Sciences (Grant No.: 93190) and registered at the Iranian Registry of Clinical Trials (Registration ID: IRCT2015041521780N1). The present study was carried out on patients referring to the Department of Endodontics, Tabriz Faculty of Dentistry from September 2014 to April 2015. The patients were unaware of the technique used for endodontic treatment, and visual analog scale (VAS) data analysis was carried out by a blinded operator. Therefore, the study was carried out in a double-blind manner.α=0.05 and a study power of 80%. The sample size was estimated based on the results of a pilot study. The final sample size was calculated to be 96 subjects, with 48 mandibular molars in each group by considering the results of the plot study and considering The inclusion criteria consisted of otherwise healthy subjects requiring endodontic treatment on mandibular first or second molars with asymptomatic irreversible pulpits with normal periapical radiographic views as shown in Pulp vitality and periradicular status of each tooth was evaluated with thermal and electric pulp tests , followed by palpation and percussion and periodontal charting. Periapical radiographies  were used for further examinations with Rinn XCP devices  and a digital radiographic system  and processed and archived by a special scanner and software interface . Clinical and radiologic data were analyzed by three independent and blinded operators.After selecting 96 eligible subjects, a clinician blinded to the treatment in each group randomly divided them into two equal groups of 48 subjects each. The two groups were matched regarding gender and the number of mandibular first and second molars with 3 and 4 root canals. Before initiating the study procedures, the advantages and outcomes of the procedures were thoroughly explained to the subjects and informed written consent was obtained from each subject in both groups. The patients were categorized in treatment groups by selecting a pocket that indicated the method of instrumentation. Endodontic proceduresInferior alveolar nerve block anesthesia was administered with injection of 1.8 mL of lidocaine containing 1:80000 epinephrine , followed by buccal infiltration of long buccal nerve for easier replacement of rubber dam. After numbness of the lip, cold and electric tests were used to confirm pulpal anesthesia. In cases with no local anesthesia, supplementary injections  were used, which was recorded in patient forms. After confirmation of anesthesia, access cavity preparation, observation of pulpal hemorrhage and confirmation of pulp vitality, the tooth was isolated with rubber dam. The root canal orifices were located. In group one, RaCe rotary instruments were used to prepare the root canals using modified crown-down technique according to the manufacturer’s instructions. The working length (WL) was estimated with the use of a preoperative radiographies, using #10 hand K-file . In order to prepare the coronal and middle thirds of the root canals, 40/0.10, 35/0.08 and 30/0.06 files were used. The WL was meticulously determined with the use of Root ZX apex locator  and a #10 hand K-file, which was confirmed with the use of a digital radiographies.The apical third of the root canals was prepared with a 25/0.02 files up to the WL. If resistance was encountered, #15 and #20 hand files were used, and preparation was followed by the use of 25/0.04 and 25/0.06 instruments. In cases where the #20 hand file did not reach the WL, the sample was excluded from the study. Apical preparation of the mesial and distal root canals of molars with 4 root canals and the mesial root canals of molars with 3 root canals continued up to 30/0.04 files. In molars with 3 root canals, apical preparation of the distal root canal continued up to 35/0.04 file. In the manual root canal preparation group, root canal preparation continued with stainless steel hand K-files and K-Flexofiles using the step-back technique. At this stage, the presence of a glide path at the coronal zone of the root canals were evaluated at the estimated WL with the use of a preoperative radiography using a #10 hand K-file. The WL was determined with a Root ZX apex locator, using a #10 hand K-file and confirmed by a digital radiographic system. Preparation of the apical third began with the use of the largest file, considered as the initial file, which reached the full WL determined with the use of the electronic apex locater and radiography. Preparation continued up to three sizes larger than the initial file, which was considered as the master apical file (MAF). Hand K-files #10 and 15 and #20, 25 and 30 Flexofiles were used to prepare the apical thirds of mesial and distal root canals of molars with 4 root canals and files #35 were used to prepare the apical thirds of distal root canals of three-rooted molars. The middle and coronal thirds of the root canals were prepared with consecutive increases in file sizes and by a 0.5-mm decrease in WL in each larger file up to 4 sizes, based on the coronal width. Files larger than the MAF were used to prepare the middle and coronal thirds with the use of feed-it-and-pull movements based on Ruddles technique, in which hand files are used with -1/4 and +1/4 apical movements up to a point at which resistance is encountered, followed by slow backward pulling of the files so that the debris is removed from the root canal. This procedure continued to reach the target root canal length with each file [After preparation procedures, the root canals were dried with paper points and obturated during the same session using lateral compaction of gutta-percha  and AH-Plus sealer . Finally, the access cavity in each tooth was sealed with eugenol temporary dressing  and the patient’s occlusion was checked to make sure that the temporary dressing did not interfere with occlusion. i.e. one picture for each time interval.Postoperative pain was evaluated with VAS. VAS consisted of a straight line graduated from 1 to 100 and is used to evaluate pain severity from “no pain” to the “most severe pain conceivable”. The severity of pain is marked on the line by patients at each of the time intervals . The picData on pain was recorded by the patients at 4-, 8-, 12-, 24- and 48-h and 1-week intervals. The patients were instructed to take mild analgesics (400 mg of ibuprofen)  in case of pain. Patients taking 400 mg of ibuprofen during the first 24 h in each group were considered to have moderate pain  and since its analgesic effect completely disappears in 8 h , these pData were analyzed with repeated-measures ANOVA, using SPSS software . Post hoc tests were used for two-by-two comparisons. Statistical significance was set at 0.05.P<0.001). A total of 118 patients contributed to this study. Four patients were missed because of not filling out the VAS forms and 18 were excluded based on the exclusion criteria of the study . In bothP=0.84). In this context, the mean pain severity scores 4 h after treatment were 26.91±4.20 in the RaCe group and 34.39±4.62 in the K-Flexofile group. After 8 h, the pain severity scores were 20.14±3.94 and 23.31±3.89 in the rotary and hand file groups, respectively. The pain severity at both intervals in the rotary group was less than the hand file group, but the difference was not statistically significant (P>0.05). At 12-, 24- and 48-h and 1-week intervals, either, the differences in pain severity between the two groups were not significant (P>0.05)  .P=0.61). Despite more severe postoperative pain during the first 8 h in the hand file group, the rate of decrease in pain severity was higher in this group compared to the rotary file group. On the other hand, during the first 4 h, 11 subjects (22.9%) in the rotary file group and 9 subjects (18.8%) in the hand file group had no pain, with no significant differences between the two groups in the number of pain-free subjects at any time interval (P=0.12).The number of patients taking analgesics during the first 24-h postoperative period was 22 (45.8%) and 15 (31.3%) in the hand and rotary file groups, respectively, with no significant differences between the two groups  and calcitonin gene-related peptide (CGRP). In this context, Caviedes-Bucheli et al.  evaluateet al. . In addiet al. . Moreoveet al. .In the present study, the pulp and periapical status of the teeth were matched in both groups to prevent the possible effect of inflammatory mediators on postoperative pain with the use of rotary system and hand files.Researchers attributed differences in the extrusion of debris from the root apex to differences in root canal preparation techniques, cervical preflaring, type of tooth and instrument designs -36. The in vitro study by Yeter et al. [in vitro study, Vaudt et al. [In an r et al. , there wt et al. , comparet et al. . Similart et al. , 6. In at et al. . Howevert et al.  in manuaAnother important consideration in the present study was comparison of the time required to prepare the root canals in the rotary and hand file groups. Despite the use of more numerous rotary files compared to the routine procedures in the rotary group, root canal preparation with hand K-Flexofiles took longer compared to that with RaCe rotary system; therefore, there was longer contact with root canal walls, resulting in the production of more debris and more manipulation of the apical area and increasing the postoperative pain in hand file group during the first 8 h.Considering the lack of significant differences in the severity of postoperative pain between the RaCe rotary and hand K-Flexofiles, it appears use of the crown-down technique is more effective in postoperative pain than the file type. Therefore, it is suggested that future studies evaluate the hand and rotary files with the same crown-down technique in both groups.


The Keele STarT Back Tool was designed for primary care medical physicians in the UK to determine the risk for persistent disabling pain in patients with musculoskeletal pain and to tailor treatments accordingly. In medical and physical therapy settings, STarT Back Tool’s tailored care plans improved patients’ low back pain outcomes and lowered costs.Review studies using the STarT Back Tool in chiropractic patient populations.PubMed, The Cochrane Library, Index to Chiropractic Literature, and Science Direct databases were searched. Articles written in English, published in peer-reviewed journals, that studied the STarT Back Tool in patients seeking chiropractic care were included.Seven articles were selected based on inclusion and exclusion criteria. The STarT Back Tool was feasibly incorporated into 19 chiropractic clinics in Denmark. Total STarT Back 5-item score correlated moderately with total Bournemouth Questionnaire score. Two studies reported that the STarT Back Tool’s predictive ability was poor, while another reported that the tool predicted outcomes in patients scoring in the medium and high risk categories who completed the STarT Back 2 days after their initial visit. A study examining Danish chiropractic, medical and physical therapy settings revealed that only baseline episode duration affected STarT Back’s prognostic ability across all care settings. The tool predicted pain and disability in chiropractic patients whose episode duration was at least 2 weeks, but not in patients with an episode duration <2 weeks.While the STarT Back Tool can be incorporated into chiropractic settings and correlates with some elements of the Bournemouth Questionnaire, its prognostic ability is sometimes limited by the shorter low back pain episodes with which chiropractic patients often present. It may be a better predictor in patients whose episode duration is at least 2 weeks. Studies examining outcomes of stratified care in chiropractic patients are needed. In the past 2 decades, health professionals have become increasingly aware of the biopsychosocial nature of sickness and disease, and more specifically, the biopsychosocial nature of pain –4. ScreeA tool known for its brevity, ease of use, and ability to detect multiple predictors of persistent disabling back pain is the Keele STarT Back Screening tool (SBT) , 7. It wThe SBT score categorizes patients into 3 risk levels for persistent symptoms: low, medium, and high , 8. The The STarT Back protocol for patients with low risk entails educating the patient about pain, encouraging movement and functional activities, reassuring the patient that the prognosis is good, and not providing any further treatment at that time. Patients with medium risk are referred for a course of physiotherapy that might include manual therapy, specific exercises, or general functional activities to prevent disability. Patients with high risk are referred to a physiotherapist for a combination of manual therapy or exercises, and a cognitive behavioral approach to overcoming psychosocial barriers to recovery , 7, 9–13Participants in primary care medical and physical therapy settings who received care according to STarT Back stratified care plans incurred lower medical costs and better clinical outcomes than those receiving usual care for nonspecific low back pain , 12, 13.Thus far, evidence is inconclusive for the benefit of using formal instruments or less formal clinical prediction rules to predict who will benefit from spinal manipulative therapy –16. It’sth, 2016. Preliminary searching of the terms start back tool on PubMed was done to gauge the number of studies conducted on the SBT across disciplines. This preliminary search yielded 78 articles. The search terms used in PubMed, The Cochrane Library and Index to Chiropractic Literature were start back screening tool AND chiropractic. This same strategy executed in Science Direct yielded 323 papers, with a more targeted search (“start back screening tool” AND chiropractic) narrowing the yield to 11 articles. On April 2, 2017, the following additional search terms were used in PubMed to ensure rigor: , , , and .A search of PubMed, The Cochrane Library, Index to Chiropractic Literature (ICL), and Science Direct databases was conducted without limits through March 29STarT Back Tool or STarT Back Screening Tool were mentioned as a part of the study design. If those terms weren’t found in the abstract, the full manuscripts were retrieved, and the methods sections were analyzed for the same SBT terms. Articles that met the inclusion criteria were analyzed. Inclusion and exclusion criteria are described in Table After the 4 databases were searched, yields were examined. Figure This narrative review did not systematically synthesize the data, nor appraise the quality of the included studies prior to inclusion. Rather, the titles, authors, respective years of publication, objectives, study designs, number of participants, settings and locations, sample characteristics, primary outcomes, main results, and limitations were extracted.n = 36) and those that didn’t fit inclusion criteria (n = 14). Table PubMed (5 searches yielding 41 articles), Cochrane Library (1 article), Index to Chiropractic Literature (4 articles), and the modified Science Direct (11 articles) searches yielded 57 articles. Seven articles were chosen for review after removing duplicate articles  –21, 22. Furthermore, in the Irgens study , there wHowever, none of the studies in this review implemented or examined STarT Back stratified care pathways. For patients who score in the low risk category, The STarT Back Protocol provides nothing more than a session of home advice, education about pain, and encouragement to continue physical activity . SpecifiAlthough the SBT was first developed to aid primary care medical physicians in determining best care pathways for patients with LBP, the SBT may be useful in stratifying care pathways for chiropractic clinicians. In many countries such as the US, Canada, and Great Britain, doctors of chiropractic are primary-contact providers , 31, 32.This review offers an assimilation of studies using the SBT in a chiropractic setting, but a number of limitations exist. First, this was a narrative review, so systematic methods of quality appraisal were not applied when selecting and reviewing manuscripts, and some articles may have been missed. One study was a secondary analysis, and no randomized controlled trials were available at the time of review. Therefore the strength of available evidence was low. Finally, letters to editors, conference proceedings, and other non-peer reviewed articles were excluded, which may have resulted in neglecting relevant information and discourse.Although the SBT lacked strong predictive value in short episode duration patients, perhaps a better focus for future research would be to explore the outcomes of stratified care in a broad range of chiropractic settings, particularly in light of the stratified care benefits reported in primary care medical settings , 13. As According to the current literature, the predictive ability of the SBT in medical and physical therapy patients translated only in some patients in some chiropractic settings, possibly due to the short episode duration with which many chiropractic patients present. In studies within medical and physiotherapy settings, stratification resulted in improved outcomes such as pain, disability, fear avoidance beliefs, and depression , 12, 13,


Much is known concerning the underlying mechanisms of Parkinson’s disease (PD) with depression, but our understanding of this disease at the neural-system level remains incomplete. This study used resting-state functional MRI (rs-fMRI) and independent component analysis (ICA) to investigate intrinsic functional connectivity (FC) within and between large-scale neural networks in 20 depressed PD (dPD) patients, 35 non-depressed PD (ndPD) patients, and 34 healthy controls (HC). To alleviate the influence caused by ICA model order selection, this work reported results from analyses at 2 levels (low and high model order). Within these two analyses, similar results were obtained: 1) dPD and ndPD patients relative to HC had reduced FC in basal ganglia network (BGN); 2) dPD compared with ndPD patients exhibited increased FC in left frontoparietal network (LFPN) and salience network (SN), and decreased FC in default-mode network (DMN); 3) dPD patients compared to HC showed increased FC between DMN and LFPN. Additionally, connectivity anomalies in the DMN, LFPN and SN correlated with the depression severity in patients with PD. Our findings confirm the involvement of BGN, DMN, LFPN and SN in depression in PD, facilitating the development of more detailed and integrative neural models of PD with depression. Converging evidence indicates that depression in PD may be a consequence of the neurodegenerative process of the disease rather than a reactive process to the chronic, disabling symptoms3. Depression associated with reduced functioning and cognitive impairment is a key determinant of poor health-related quality of life in patients with PD4. Understanding depression in patients with PD is, therefore, crucial to achieve the optimal diagnosis and treatment that is needed for patients with this disease.Depression is one of the most common non-motor symptoms of Parkinson disease (PD), with a prevalence of around 35%9. Those findings lend support to the viewpoint that prefrontal cortex, basal ganglia (BG), and limbic system are involved in dPD. More recently, resting-state fMRI (rs-fMRI), as a novel non-invasive approach to measuring baseline brain activity and connectivity, has been increasingly utilized to uncover the neural underpinnings of dPD14. Those rs-fMRI studies using the amplitude of low-frequency fluctuation (ALFF) and regional homogeneity (ReHo) methods highlighted that dPD patients had abnormal resting brain activity in the prefrontal and limbic regions, such as amygdala, OFC, DLPFC, MPFC, ACC, compared with non-depressed PD (ndPD) patients14. Also reported were aberrant resting brain connectivity between regions of OFC-insula, OFC-amygdala, middle temporal gyrus (MTG)-putamen, amygdala-putamen, median cingulate cortex (MCC)-MPFC, and MCC-PCC/precuneus (PCC/PCu)14, suggesting disrupted functional integrity in prefrontal, cingulated, BG, and limbic areas in dPD patients. Overall, the above neuroimaging findings allow us to propose that depression in PD could depend on the damage to specific neural networks rather than on the dysfunction of single, discrete brain region. Attempting to understand dPD from a network-level perspective, hence, may yield an incremental advancement to existing neural models of dPD. Although former researchers using region-of-interest (ROI) approach have noted the potential benefits of exploring dPD at the neural-system level14, neural network disruption in dPD remains largely obscure.Functional neuroimaging investigations of depression in PD can advance both the diagnosis biomarkers and treatment evaluation of this debilitating illness. With positron emission tomography (PET), single-photon emission computed tomography (SPECT), and task-based functional magnetic resonance imaging (fMRI), functional anomalies in several brain regions are related to depressed PD patients (dPD), including the dorsolateral prefrontal cortex (DLPFC), medial prefrontal cortex (MPFC), orbitofrontal cortex (OFC), anterior cingulate cortex (ACC), insula, thalamus, amygdala, ventral striatum, and caudate16. The study of RSNs or ICNs has already been shown to be of great potential clinical value, providing rich and sensitive markers of PD19. To our knowledge, no study so far has investigated it in dPD. Given that several prefrontal, cingulated, BG, and limbic regions are well documented to be implicated in dPD13, this study sought to determine (1) whether the corresponding neural networks composed of these regions displayed aberrant interactions within each network and between them (intra- and internetwork connectivity) in dPD patients by comparing with ndPD and healthy subjects and (2) if so, whether the detected aberrant interactions between dPD and ndPD patients were related to the severity of depression in PD. To address the aforementioned issues, ICA method was performed to isolate the ICNs comprising of BG network (BGN), default-mode network (DMN), salience network (SN) and frontoparietal network (FPN), which cover large parts of the prefrontal, cingulated, BG, and limbic areas relevant to dPD13. In consideration of ICA model order selection having a significant effect on ICN’s characteristics20, this study acquired ICNs at 2 decomposition levels. The first is a relative lower ICA decomposition estimated using minimum description length criterion21, and the second is a higher ICA decomposition that has been applied in previous studies22. At each decomposition level, functional connectivity within each individual network was evaluated using the corresponding ICN’s spatial z-maps. Interactions among networks were measured by Pearson’s correlation between ICN’s time courses23. Relationship between abnormalities of intra- and internetwork connectivity and clinical severity in patients with PD was assessed by Spearman correlation analysis. The results of this study will contribute to our knowledge of the neural network disruption in PD with depression.Independent component analysis (ICA), as a powerful data-driven approach with no a priori definition of seed regions, offers an effective means for identification of functional systems within the brain during rest, typically referred to as “resting state networks” (RSNs) or “intrinsic connectivity networks” (ICNs)24, the motor component of the Unified Parkinson’s Disease Rating Scale (UPDRS-III)25 score, and levodopa equivalent dose (LED) were found between dPD and ndPD patients. By definition, the Hamilton Depression Rating Scale (HDRS) scores of dPD patients were significantly higher than that of ndPD patients (p < 0.001).Demographic and clinical features of the sample were listed in Table 26.At the 28-component level, the spatial maps of the 5 selected ICNs for each group are shown in Fig. BGN: putamen, caudate, pallidum, and thalamus.DMN: MPFC, PCC/PCu, medial and lateral temporal cortex, lateral parietal cortex (LPC).Right/Left FPN (RFPN/LFPN): right/left posterior parietal cortex (PPC), and right/left DLPFC.SN: anterior insula, ACC, and several subcortical and limbic structures.27 corrected, Fig. BGN, DMN, LFPN, and SN were found to display altered functional connectivity among the dPD, HC and ndPD groups 29, including anterior DMN , inferior-posterior , and superior-posterior DMN . The BGN, SN, LFPN, and RFPN were represented in one component, respectively. The selected ICNs were shown as Supplementary Fig. 20. The different spatial features and z-score distribution for the chosen components can affect the subsequent cluster-level FDR correction.At the 70-component level, 7 components were identified as the most representative ICNs for BGN, DMN, LFPN, RFPN, and SN. The DMN was represented in 3 componentsAt the 28-component level, connectivity between BGN and DMN, and between bilateral FPN and DMN were altered among the three groups Fig. , Table 430 and post-hoc analysis. No significant differences were found between dPD and ndPD patients, and dPD patients relative to healthy subjects had altered connectivity between DMN and LFPN, in line with the above mentioned results obtained using the interested 5 or 7 components. Besides, compared to healthy controls, both dPD and ndPD patients had abnormal connectivity between BGN, sensorimotor, auditory, visual, and frontal networks. These results may explain the motor, visual, and auditory disturbance exhibited by all PD patients. More details were presented in Supplementary Table At the 70-component level, we also used the identified 26 components , and then these results were applied to correlated with clinical severity in patients with PD. Connectivity in the detected regions of BGN, DMN, LFPN, and SN were used for correlation analysis with the UPDRS-III and HDRS scores in all PD patients. The results showed that (1) connectivity in the BGN was uncorrelated with the UPDRS-III and HDRS scores; (2) connectivity in the DMN was correlated negatively with the HDRS scores, and connectivity in the LFPN and SN was correlated positively with the HDRS scores; (3) connectivity in the DMN, LFPN and SN was uncorrelated with the UPDRS-III scores Fig. . For patSince dPD and ndPD patients did not show any significant differences in internetwork connectivity, the correlation analysis between internetwork connectivity and the UPDRS-III and HDRS scores were not performed on the whole PD group. Besides, we exam the correlation between DMN and LFPN connectivity and the UPDRS-III and HDRS scores in dPD subgroup, as dPD compared to HC exhibited enhanced connectivity between DMN and LFPN. Connectivity between DMN and LFPN was uncorrelated with the UPDRS-III  and HDRS scores  in dPD. Moreover, connectivity between aDMN and LFPN, and between ipDMN and RFPN, obtained using high model order ICA, were uncorrelated with the UPDRS-III  and HDRS scores  in dPD.In the current study, we applied rs-fMRI combined with two ICA decomposition methods to explore intrinsic connectivity changes within and between large-scale neural networks in PD with depression. Similar results can be obtained using these two decomposition algorithms: 1) dPD and ndPD patients relative to healthy subjects had decreased BGN connectivity; 2) dPD patients compared with ndPD patients exhibited increased LFPN and SN connectivity, and decreased DMN connectivity; 3) dPD patients in contrast to healthy controls showed hyperconnectivity between DMN and LFPN. Furthermore, connectivity abnormities in the DMN, LFPN and SN correlated with the severity of depression in PD. Our results confirmed the BGN, LFPN, DMN, and SN dysfunction associated with depression in PD.31. In patients with PD, the degeneration of dopaminergic neurons in the substantia nigra pars compacta triggers a cascade of functional changes affecting the whole BG network32. Dopaminergic changes in BG network are responsible for the development of the cardinal motor features in PD, such as tremor, rigidity, and akinesia33. However, the dopaminergic degeneration in BG circuit was not thought to be associated purely with motor control in PD. Previous studies with PET or SPECT have found that depressed PD patients are related to dopamine loss in the striatum34, indicating the role of BG dopaminergic circuit in the occurrence of depression in PD. Indeed, the BG is intimately connected with the cortex through several segregated but parallel loops, which have been subdivided into motor, associative (cognitive), and limbic  domains35. They deal with the control of movement, behavior and cognition, and reward and emotions35, respectively. Dysfunction of nonmotor BG circuit has been proposed to explain the mood disturbances exhibited by PD patients36. In the present study, we found dPD and ndPD patients had reduced BGN connectivity, demonstrating that functional disruption in BGN was a common pathological change in depressed and non-depressed PD patients, and reinforcing the view that the BG dopaminergic circuit plays an essential part in the pathogenesis of depression in PD.The BG subserves a wide range of functions, including motor, cognitive, motivational, and emotional processes, and disruption of this circuit has been implicated in numerous neurological and psychiatric disorders37, and impairment in this network contributes to the characteristic symptom of self-focused rumination in primary depression39. Although the involvement of DMN in primary depression is well documented, its role in PD with depression remains uncertain. To our knowledge, only three rs-fMRI studies have delineated the role of DMN in depression in PD. Two rs-fMRI studies reported that dPD exhibited abnormalities in the nodes of DMN, such as decreased ALFF value in the ventral MPFC14, and increased eigenvector centrality (EC) value in the PCC40, supporting the DMN impairment related to depression in PD. While another rs-fMRI study found that both dPD and ndPD patients had connectivity alterations in the DMN (e.g. PCu)12, demonstrating the DMN dysfunction is a common pathological condition in PD. A former literature provided further evidence for the above viewpoint by showing that there was an early functional disruption of the DMN in cognitively unimpaired PD patients19. Taken together, previous findings on the DMN dysfunction in depression in PD are contradictory. Here we found dPD patients had reduced DMN connectivity (e.g. LPC) relative to ndPD patients, in accordance with previous two rs-fMRI studies40, lending support to the DMN dysfunction relevant to depression in PD. The current result may indicate that depressed PD patients, like patients with primary depression, had a failure to normally regulate self-referential activity due to the DMN’s impairment41. As mentioned above, conflict findings are reported with respect to the role of DMN in PD with depression, and thus the present result of abnormal DMN connectivity involved in depressed PD should be further validated.The DMN is a constellation of brain regions characterized by functions of self-referential processes42. Abnormal communication within the FPN may underlie deficits in cognitive control and emotional regulation in primary depression42. The DLPFC including portions of the middle and superior frontal gyrus on the lateral surface of the frontal lobes is a key component in FPN, and dysfunction of this area has been recognized as a hallmark for the pathophysiology of depression in PD46. SPECT and PET studies found that dPD patients exhibited increased blood flow45 and serotonin transporter density44 in the DLPFC. Two rs-fMRI studies reported that dPD patients had reduced ALFF14 and EC40 value in the DLPFC. Moreover, the DLPFC was identified as a potential therapeutic target for dPD patients43. Those findings demonstrate the association of DLPFC dysfunction with depression in PD. This study found dPD patients exhibited increased connectivity in the DLPFC, adding to the growing evidence for the DLPFC disruption devoted to the presence of depression in PD. According to former literature, dysfunction of the DLPFC involved in dPD patients may be secondary to pathology in the dopaminergic projections from the ventral tegmental area (VTA) to the prefrontal cortex47. Consequently, dopamine depletion in the mesocortical pathway could be used to explain the altered DLPFC connectivity with dPD in our study. Since the DLPFC anomalies are secondary to prefrontal dopaminergic deficiency, patient’s dopaminergic state (“ON” or “OFF”) would influence connectivity patterns in this region. Two fMRI studies have demonstrated administration of levodopa relatively normalized the DLPFC connectivity in PD49. This is one possible cause for the DLPFC changes in opposite direction in our study (“ON” state) compared with previous two rs-fMRI studies (“OFF” state)40. Another possible cause is that ICA-derived functional connectivity is distinct from the ALFF and EC index. ALFF approach measures regional cerebral activity changes12. EC technique is similar to node degree, aimed to identify a prominent or diminished role of a specific region in whole brain network50, which is differ from the ICA method aimed to divide the whole brain into several subnetworks.The FPN consisting of DLPFC and PPC takes the charge of top-down regulation of attention and emotion26. Abnormalities of SN lead to an impaired salience processing, contributing to the onset and maintenance of depressive symptom in general population52. Investigators have found greater activation in depressed than in non-depressed subjects in the nodes of SN (e.g. insula and ACC) across a wide range of negative conditions55. The SN involved in PD with depression has also been demonstrated in several studies. For instance, previous PET studies revealed ACC hypometabolism associated with depression in PD56. Depressed PD patients exhibited a specific loss of dopamine and noradrenaline innervation in the ACC57. In addition, microstructural changes in the ACC bundles were related to dPD patients59. In this study, depressed PD patients had increased connectivity in the ACC, adding to evidence that ACC could play a major role in the pathogenesis of depression in PD. The involvement of ACC dysfunction in depressed PD, as described in former research, can attribute to the degeneration of the mesolimbic dopaminergic system in dPD patients57. The current result of increased ACC connectivity in dPD patients, thus, may ascribe to their mesolimbic dopaminergic dysfunction. Within the SN, an anomalous function of the ACC is among the most consistent findings in depressed PD patients. The question of whether other primary nodes of the SN (e.g. anterior insula) affected in dPD needs to be further investigated.The SN with its robust connections to several limbic and subcortical structures has been conceptualized as a bottom-up processor of salient experiences60. Here we discovered reduced anticorrelation between DMN and LFPN in dPD, in keeping with previous findings on patients with primary depression, suggesting inappropriate engagement of anticorrelated networks is a generic marker for the development of depressive symptoms. Abnormal communication between DMN and FPN implicated in dPD can be also validated by using high model order ICA, even though the relationship between DMN’s subsystem and FPN was partially reorganized. These reorganized internetwork connectivity patterns found in our sample correspond with previous high model order ICA studies29. The current findings needs to be further testified due to the lack of study on the relationship between ICNs in dPD.In addition to the above mentioned intranetwork connectivity abnormities associated with dPD, dPD patients had enhanced connectivity between LFPN and DMN compared to healthy subjects. Specially, we found that the correlation between DMN and LFPN was negative in healthy controls but positive in dPD patients, indicating that normal reciprocity (anticorrlation) between DMN and FPN was weakened in dPD patients. This weakened reciprocity would lead to a poor switching between DMN-based self-referential and FPN-based goal-directed processes in primary depression, accounting for depressive symptoms of patients with this disease17. This may indicate that BGN connectivity, similar to substantia nigra hyperechogenicity as identified by transcranial sonography61, is a trait and not a state biomarker of disease. Connectivity abnormalities in the DMN, LFPN and SN correlated with the HDRS scores but not with the UPDRS-III scores in PD patients, suggesting that dysfunction of the DMN, SN, and LFPN is responsible for the presence of depressive symptoms rather than motor symptoms in PD, and reinforce the hypothesis of functional disruption of the DMN, LFPN and SN involved in depression in PD.Finally, we found that connectivity anomalies in the BGN did not correlate with the HDRS and UPDRS-III scores (depressive and motor severity) in PD patients, in line with a previous rs-fMRI study presenting findings on BGN connectivity having no relationship with clinical indices of severity in PD20, computational or objective criterion is still missing. To alleviate the impact of model order selection on the results, we also conducted analysis at 28-component level based on the minimum description length criteria21. Second, the dPD (n = 20) patients sample size is relatively small. Nevertheless, dPD patients were enrolled using stringent inclusion criteria, such as recruitment of mild to moderate stage patients, no use of antidepressants and dopamine agonists, etc. Third, although the MMSE was used to exclusion of demented patients, mild cognitive impairment in patient sample cannot be fully ruled out. This issue, however, may not influence our results a great deal, since dPD and ndPD patients did not differ in terms of their MMSE scores. The Montreal Cognitive Assessment scale (MoCA) that is preferred over the MMSE for screening of mild cognitive dysfunction could be included in future studies. Fourth, the use of medication is an important confounder. However, both groups of patients were taking similar doses of dopaminergic drugs . Moreover, we performed correlation analysis between the LED and altered functional connectivity in the DMN, LFPN, and SN, and did not reveal any significant association . Finally, the lack of non-PD depression group left unanswered the question whether dysfunctional neural networks  observed in depressed PD patients were associated with depression in the general population. It does not enable us to determine whether the depression of PD shares a common neurobiological substrate with that of primary depression. Individuals with primary depression would be recruited in the future to help us better understanding of the dysfunctional neural networks in depression, PD with depression, and PD without depression.Several limitations warrant attention and suggest directions for future research. First, our selection of high model order ICA was empirical. Although it has been demonstrated that 70 components seems to be an optimal choice62. However, this hypothesis should be evaluated by future rs-fMRI studies combined with the corresponding PET/SPECT data.In summary, this study, to best of our knowledge, provides the first evidence of neural network dysfunction in depressed PD patients, including reduced connectivity in the BGN and DMN, increased connectivity in the LFPN and SN, as well as hyperconnectivity between DMN and LFPN. These neuroimaging deficits exhibited by dPD patients may attribute to dysfunction of BG dopaminergic circuits and mesocorticolimbic dopamine systems in dPD70 right-handed PD patients (21 dPD and 49 ndPD) were recruited from the movement disorders outpatient clinic of Nanjing Brain Hospital . All had a diagnosis of idiopathic PD by an experienced neurologist according to the UK Parkinson Disease Society Brain Bank Criteria. To minimize the impact of head motion, PD patients were studied while taking their usual medications (“ON” state). Exclusion criteria were: (1) moderate to severe head tremor; (2) cerebrovascular disorders, including previous stroke, history of head injury, history of seizure, hydrocephalus, intracranial mass, previous neurological surgery and other neurologic diseases; (3) antiparkinsonian treatment with dopamine agonists, (4) antidepressant treatment or other psychiatric therapy; (5) Mini Mental State Examination (MMSE) score < 24; and (6) incomplete clinic information. 4 ndPD patients were excluded from the present analyses due to the stringent exclusion criteria. The remaining 66 PD patients were on stable dopaminergic treatment for at least 4 weeks prior to study entry. In addition, 50 right-handed healthy controls (HC) were recruited from local individuals who volunteered to participate in scientific studies. 1 HC with MMSE <24 were discarded. The remaining 49 control subjects had a normal neurological status with no history of either neurological or psychiatric diseases. Table Psychometric and neurologic assessments with all PD patients were done in the “ON” state, i.e. with their usual antiparkinsonian medication. Each patient’s disease severity was measured by H&Y stage and UPDRS-III. Only mild to moderate stage patients were enrolled in the study in order to complete a long scan. Non-depressed patients were matched with depressed patients on the basis of disease severity. Diagnosis of depression was using the Diagnostic and Statistical manual of Mental Disorders, Fifth Edition (DSM-V) criteria by an experienced, board-certified psychiatrist trained for Structured Clinical Interview. The severity of depression was evaluated using the 17-item Hamilton Depression Rating Scale (HDRS-17). All depressed PD patients had a HDRS-17 score higher than 14 points. All the subjects were administered the MMSE, and individuals with MMSE score <24 were not included. Data pertaining to age, gender, handedness, education level, disease duration, and clinical symptom ratings were collected by a movement disorder specialist prior to MRI examination.All the patients were in the “ON” state before and during scanning. Image data were acquired using a Siemens 3.0-Tesla signal scanner . Subjects were instructed to stay awake and close their eyes, and to try not to think of anything. Functional imaging data were collected transversely by using a gradient-recalled echo-planar imaging (GRE-EPI) pulse sequence with the following settings: TR/TE = 200 ms/30 ms, flip angle = 90°, matrix = 64 × 64, FOV = 220 mm × 220 mm, thickness/gap = 3.5 mm/0.6 mm, in-plane resolution = 3.4 mm × 3.4 mm, slices = 31. For each subject, a total of 140 volumes were obtained, resulting in a total scan time of 280 s. High resolution anatomical images were acquired using a T1 fluid attenuated inversion recovery (FLAIR) sequence .http://www.fil.ion.ucl.ac.uk/spm/). Then the segmented tissue class images  were employed to generate a group-specific template  using DARTEL toolbox in SPM12. The subject-specific flow fields yielded from the DARTEL procedure can be applied to corresponding functional data in the next stage.Structural images were reoriented to the anterior commissure and segmented into grey matter (GM), white matter (WM), cerebrospinal fluid (CSF), skull, and soft tissue outside the brain, using the standard segmentation option in SPM 12 (http://afni.nimh.nih.gov/afni) packages. The steps including slice acquisition correction, head motion correction, spatial normalization, and smoothing were performed with SPM 12, and the dispike procedure was achieved in AFNI software. Briefly, the first 5 volumes were discarded to allow for magnetization stabilization. The remaining 135 consecutive images were then corrected for the acquisition delay between slices using the middle slice as the reference frame and further realigned to the first volume to correct for head movement with SPM12. 6 subjects (3 HC and 3 ndPD) with head motion exceeding ± 2.5 mm of translation or ± 2.5 degrees of rotation were excluded from the dataset. To minimize the impact of motion artifact on functional connectivity analysis63, 20 subjects  with excessive instantaneous head motion (mean framewise displacement (FD) exceeding 0.3) were discarded, resulting 20 dPD, 35 ndPD, and 34 HC for the following analyses. The instantaneous head motion was calculated using the six head realignment parameters, as described in63. The motion-corrected volumes were then despiked using AFNI’s 3dDespike algorithm to mitigate the impact of outliers. The mean functional image across all realigned volumes was coregistered with the structural image, and the resulting warps applied to all the despiked functional volumes by utilizing SPM12. Finally, all the coregistered functional images were nonlinearly normalized, subject by subject, to the sample-specific group template (using subject-specific flow fields), affine-aligned into stereotactic space of the Montreal Neurological Institute (3 mm isometric voxel size), and smoothed using a 6 mm full-width at half maximum Gaussian filter64. In addition, six head motion parameters obtained in the realigning step, WM signal, CSF signal, and Legendre polynomials orders up to 2nd were included in a linear regression to remove possible spurious variances from the data. CSF and WM mean signals were determined by averaging the native-space functional time series of all voxels contained inside the corresponding masks obtained from the segmentation of the structural images using DARTEL.Resting-state functional images preprocessing was carried out using both SPM12 and AFNI  data reduction, (2) group ICA, and (3) back reconstruction. First, principal components analysis (PCA) was applied to reduce the data dimensionality for each subject. The reduced data from all subjects were then concatenated and entered into a second data reduction step using PCA. Second, the reduced, group concatenated data were entered into the ICA algorithm (Infomax)66 to calculate spatially independent group components. The number of independent group components was set at 28 and 70 respectively, based on the minimum description length criterion described in23 and high model order ICA used in22. The reliability of the independent components decomposition was tested by running Infomax 20 times in the ICASSO toolbox67. Third, individual subject components were back reconstructed from the group components using GICA approach65, during which the aggregate components and the results from data reduction step were used to compute the individual subject components. Each back-reconstructed component consists of a spatial z-map reflecting component’s functional connectivity pattern across space and an associated time course reflecting component’s activity across time. The group-level components corresponding to BGN, DMN, SN, and bilateral FPN, were selected by visual inspection and confirmed using the template-matching procedure68. The template for BGN, DMN, SN, and FPN was provided in GIFT software (the RSN template), and the map of each component was spatially correlated with specific network template. The component with largest spatial correlation coefficients with each of these templates was chosen and reconfirmed by visual inspection. To further confirm our selected ICNs, we also generated the network templates using the WFU Pickatlas69 on the basis of the Brodmann areas and cluster peaks reported in the literature . Spatial correlation was performed between the components and the generated templates. For high model order ICA, the RSN template, the generated network template, and the template came from online T-maps of 28 components29  was employed to match with our 70 independent components’ spatial maps. The subsystems of BGN, DMN, FPN, and SN were chosen based on the largest spatial correlation with these templates. Functional connectivity within each selected ICN was calculated using the reconstructed component’s spatial z-maps.Preprocessed images were analyzed with the Group ICA of fMRI Toolbox (GIFT) software23. Correlation coefficients were then transformed to z-scores using Fisher’s z-transformation. At the 28-component level, the number of pair-wise combinations is 10 for each subject as 5 components were identified. At 70-component level, 7 components were identified as the most representative ICNs for BGN, DMN, LFPN, RFPN, and SN, and the number of pair-wise combinations is 21 for each subject.To evaluate functional connectivity between the selected ICNs, subject specific ICN’s time courses were detrended, despiked, filtered using a fifth-order Butterworth low-pass filter with a high frequency cutoff of 0.15 Hz, and pairwise correlated by Pearson’s correlation, following the approach of Jafri and colleagues29. The NBS method and post-hoc analysis was applied to determine connectivity changes between three groups.To further verify the internetwork connectivity, we also used the identified 26 components derived from 70 components to conduct the internetwork connectivity analysis. The identified 26 components reflected the BGN, DMN, auditory, visual, sensorimotor, attention, and frontal networks, respectivelyDifferences between groups in terms of demographic and clinical variables were conducted by Pearson chi-square test, One-way analysis of variance (ANOVA), Wilcoxon rank sum test, and Student t test in SPSS software package , as appropriate. The level of statistical significance was set at P < 0.05.To statistically evaluate functional connectivity within each selected ICN, we calculated voxel-wise one-sample t-tests on participants’ reconstructed spatial maps for each group using SPM12  corrected). Comparisons of connectivity within each ICN among dPD, ndPD, and HC groups were performed by using a design model of one-way ANOVA in SPM12, followed by post-hoc two-sample t tests. The significance threshold was set at p < 0.05, corrected for multiple comparisons using topoFDR in SPM12. Between-group differences of connectivity among selected ICNs were assessed using an ANOVA model in SPSS, and post-hoc two-sample t tests were carried out to determine connectivity changes between each pair of the three groups .The correlations between the detected connectivity abnormalities and the HDRS, UPDRS-III scores were assessed for overall PD and dPD patients respectively, by using Spearman correlation coefficient. The statistical level with P < 0.05 was considered as significant.Aberrant Intra- and Internetwork Functional Connectivity in Depressed Parkinson’s Disease


P = 0.01), pain catastrophizing , relative delta  and beta EEG activity  induced by experimental cold pain. None of the study variables were related to improvement in quality of life. For the first time, individual pain processing characteristics have been linked to opioid response in a mixed chronic pain population. This has the potential to personalize treatment of chronic pain and restrict opioid use to patients with high likelihood for response.Opioids are increasingly used for treatment of chronic pain. However, they are only effective in a subset of patients and have multiple side effects. Thus, studies using biomarkers for response are highly warranted. The current study prospectively examined 63 opioid-naïve patients initiating opioid use for diverse types of chronic pain at five European centers. Quantitative sensory testing, electroencephalography (EEG) recordings, and assessment of pain catastrophizing were performed prior to treatment. The co-primary outcomes were change from baseline in ratings of chronic pain and quality of life after 14 days of opioid treatment. Secondary outcomes included patient’s global impression of clinical change and side effects. Logistic regression models adjusted for age and sex were used to identify biomarkers predictive for successful treatment, defined as at least a 30% reduction in average pain intensity or an improvement in quality of life of at least 10 scale points. Fifty-nine patients (94%) completed the study. The mean age was 55 ± 16 years and 69% were females. Pain reduction was predicted by cold pain intensity (OR: 0.69;  Chronic pain is a highly prevalent condition that may impact negatively on the individual’s quality of life; moreover, it is an expensive condition for society. Presently, chronic pain is considered as a bio-psychosocial phenomenon–a combination of physical dysfunction, beliefs, coping strategies, distress, illness behavior and social interactions. Pharmacotherapy is a cornerstone in the multimodal interdisciplinary treatment. However, chronic pain treatment still largely depends on local experience and traditions rather than individual patient characteristics , 2. ChroWe hypothesized that the most promising techniques in previous experimental, postoperative, and clinical pain studies could serve as biomarkers of chronic pain and opioid analgesia. Hence, the objective of this study was to determine whether characteristics of altered pain processing in opioid-naïve patients could be used to predict clinically relevant treatment responses to opioids. To ensure general applicability, we collected longitudinal data from heterogeneous patient populations with moderate to severe chronic pain initiating opioid use at five centers in Europe.Predictive Markers of the Effects of Opioid Therapy in Opioid-naïve Patients with Chronic Pain (ABILITY) study was a two-week observational cohort study designed to evaluate the predictive value of pre-treatment markers of opioid response in opioid-naïve patients with various chronic pain conditions. This study was conducted across outpatient clinics at four university hospitals and one private hospital in Denmark, Slovenia, and Belgium. The research team recruited participants and conducted follow-up from October 2014 to September 2015. Opioid treatment of study patients took place without randomization and followed clinical practice at each participating center to reflect the true clinical situation. Opioid treatment was determined, prescribed, modified and discontinued at the sole discretion of the treating physician at each participating center; regardless of generic name, manufacturer, constituent components, route of administration, and dosing schedule (including titration and run-in periods). Regardless of any decision to modify or discontinue their assigned opioid treatment, study subjects were retained in the study whenever possible to enable follow-up data collection and prevent missing data. Of note, previously used pain medications were continued throughout the study. If opioid treatment was discontinued as a result of an adverse event, the circumstances leading to discontinuation of treatment were documented.The The Central Denmark Region Committees on Health Research Ethics (1-10-72-132-14) and the Danish Data Protection Agency (1-16-02-300-14/2007-58-0010) approved the study. The study protocol was further approved by the local ethics committees at each participating center. Participation in the study had no impact on the patients’ current or subsequent care and treatment. All study participants gave written informed consent. No financial compensation was given at any time during study. The study is registered at the US National Institutes of Health  #02308306.Patient demographics, medical history and medications, persistent pain features, quantitative sensory testing, EEG, and situational pain catastrophizing were registered and assessed at baseline. Data on clinical efficacy and side effects were collected at 14-days after initiating opioid treatment using a mailed questionnaire.no pain) to 10 (worst pain imaginable); expected to continue opioid and any concomitant non-opioid treatment throughout the study and age >18 years. Exclusion criteria were: Mental incapacity or language barriers precluding adequate understanding of study procedures; significant serious underlying conditions or similar reasons; having received opioid(s) on a daily basis (within the last 10 weeks); current alcohol and/or substance abuse.The following main inclusion criteria were used: Pain duration ≥3 months; baseline pain intensity ≥4 and <9 on an 11-point numerical rating scale (NRS) ranging from 0   and Euro2 . Pressure was gradually increased with a rate of 30 kPa per second until a pain sensation was evoked (pressure pain detection threshold). Cold pressor pain was induced by immersion of the patient’s hand in a stirred ice water bath (1–2°C) for two minutes. Patients were asked to rate worst cold pressor pain intensity (NRS 0–10) after two minutes of hand immersion  and the pressure pain detection threshold was reassessed. The conditioned pain modulation effect was defined as the relative change in pressure pain thresholds before and after the cold pressor test. In brief, the ice water (conditioning stimulus) typically results in pain inhibition to the second pressure stimulus [Electrical pain sensitivity was assessed on the volar forearm 2 cm distal to the wrist using a computer-controlled constant current stimulator . The current intensity was gradually increased in steps of 1 mA until a sensation of pain was evoked . Pressure pain sensitivity was assessed at the subjects’ quadriceps muscle 10 cm above the patella on the same side as the dominant hand using a handheld digital pressure algometer with a probe size of 1 cmstimulus .Electrical activity of the brain was recorded during the two-minute cold pressor test via an electrode head cap with premeasured electrode placement  using a digital amplifier . Nine electrode sites and a reference electrode site were filled with Electro-Gel  and prepped to measured impedance values below 5 kohms. Pre-processing and spectral analysis of EEG dynamics have been described in detail elsewhere . In brieIn connection with quantitative sensory testing, patients completed the Pain Catastrophizing Scale with reference to the pain induced by the cold pressor test . OriginaTo date, no study has identified pre-treatment measures of opioid efficacy in opioid-naïve patients initiating opioid use for chronic pain and no a priori sample size could be calculated. The selection of clinically implementable measures for predicting opioid efficacy was therefore based on experiences from numerous clinical studies and by reviewing available literature . We aimeAnalyses included all patients who took at least one dose of opioid medication and had at least one post-treatment efficacy assessment (complete case), irrespective of whether they continued opioid and any concomitant non-opioid treatment throughout the study or stopped treatment prematurely. Repeated outcome measurements and baseline characteristics between patients with and without clinically successful treatment were compared using the Wilcoxon signed-rank test and the Wilcoxon rank-sum test, respectively. Multilevel mixed-effects logistic regression models with a random intercept by participating center identification were applied to examine the influence of selected pre-treatment measures on opioid response. In brief, mixed effects logistic regression is used to model binary outcome variables when data are clustered or there are both fixed and random effects. In this study, a variety of outcomes were collected on patients, who were nested within clinics. By taking clustering within clinics into account, odds ratios (OR) and 95% confidence intervals (95% CI) were calculated with and without adjustment for sex and age. Concerning continuous predictors, it should be noted that the coefficient is the odds ratio for successful treatment per unit of measurement of difference in the explanatory variable. Two-tailed P-values <0.05 were considered statistically significant. Stata/IC 12.1  was used for all statistical analyses.The five participating centers screened 73 patients for eligibility . A totalP = 0.01), pain catastrophizing , relative delta  and beta EEG activity  induced by experimental cold pain. In contrast, none of the study variables were predictive of improvement in quality of life Click here for additional data file.


Cultural and social factors play an important role in the development and persistence of Low Back Pain (LBP). Nevertheless, there are few studies investigating differences in LBP features between countries.To determine differences in pain perception between individuals with LBP living in Brazil and Spain.Thirty Spanish individuals and 30 age- and sex-comparable Brazilian individuals with LBP were recruited from the Public Health Services of both countries. The Numerical Pain Rating Scale and the pain rating index (PRI), the number of words chosen (NWC), and the present pain index (PPI) extracted from the McGill Pain Questionnaire were used to assess pain. The Oswestry Disability Index, the Short Form-36, Beck Depression Inventory-II, and Pittsburgh Sleep Quality Index were also applied. Differences between countries and the correlation between demographic and clinical variables in each country were assessed with parametric and the nonparametric tests.A significant Country by Gender interaction was found for the PRI total score (P=0.038), but not for intensity of pain, disability, PPI, or NWC, in which Spanish women exhibited greater pain ratio than Spanish men (P=0.014), and no gender differences were identified in Brazilians. The Spanish group showed a consistent pattern of correlations for clinical data. Within Brazilian patients, fewer correlations were found and all of the coefficients were lower than those in the Spanish group.The pain perception in patients with LBP is different depending on the country. Within Spanish patients, LBP is considered a more global entity affecting multidimensional contexts. Pain perception in chronic LBP could be different depending on the country.Spanish women present greater pain and poorer mental health than Spanish men do.Spanish patients consider that LBP affects multidimensional contexts.The potential relevance of cultural factors in chronic LBP must be determined.,Low back pain (LBP) refers to symptoms located under the costal edge and above the folds of the lower gluteus muscles with or without irradiation to the leg,,,Pain is a complex perceptive disorder associated with social and cultural factorsAlthough no representative study provides an overall prevalence of LBP in Brazil-Although it seems that cultural, social, and geographic factors play an important role in the development and persistence of LBPTherefore, the main objective of the current study was to determine the differences in pain perception between individuals with LBP living in Brazil and Spain. The secondary objective was to determine the differences in health-related quality of life, disability, mood, and sleep quality between both countries and to identify the relations between demographic and clinical data in each country.A cross-sectional design was used in this study. Thirty patients with LBP recruited from the Orthopedic Service at the São Carlos Health Unit  and 30 age- and sex-comparable individuals with LBP recruited from the Orthopedic Hospital Department at University-Hospital of Salamanca  were included. Participants were recruited through consecutive sampling. To be eligible, they had to suffer from non-specific LBP without referral into the lower extremity for more than 6 months and diagnosed by an orthopedic physician. Exclusion criteria included: 1) age less than 18 years; 2) LBP with a specific underlying medical pathology such as tumor, infection, inflammatory disorders, disc problems, and nerve root compromise; 3) diagnosis of fibromyalgia syndrome; 4) previous lumbar spine surgery; 5) diagnosis of psychiatric illness; 6) presence of other musculoskeletal diagnosis at the time of the study; or 7) refusal to participate in the study. The medical history from each patient was requested from their primary care physician to assess the presence of the exclusion criteria. The same interviewer (DPRS), who was bilingual in Brazilian and Spanish languages and had 6 years of clinical experience, conducted the data collection in both countries. All of the questionnaires were self-administered.All participants read and signed an informed consent form before their inclusion in the study. The current study was conducted following the Declaration of Helsinki and was approved by the Ethics Committee of the University of Salamanca, Salamanca, Spain (code number: 7/2-12). In addition, clinical services of both countries accepted these ethical considerations following an international ethical agreement between both countries.An 11-point numerical pain rating scale  was used to assess the mean intensity of pain experienced in the last weekThe McGill Pain Questionnaire (MPQ) was used to assess pain intensity. Items were joined to achieve three main domains of the questionnaire, i.e., sensory (1-15), affective (16-18), and evaluative (19), as well as the total score or pain rating index (PRI) for each domain. We also considered the number of words chosen by the patient (NWC) and the present pain index (PPI), which describes current pain intensity from 0 (no pain) to 5 (excruciating pain) scales. In the current study, we used the Spanish,,The ODI is one of the most frequently used tools for measuring LBP-related disabilityThe health-related quality of life was assessed with the Medical Outcomes Study Short Form 36 (SF-36) questionnaire, which assessed eight domains: physical functioning, role physical, bodily pain, general health, vitality, social functioning, role-emotional, and mental healthThe SF-36 questionnaire can be also summarized as two health measures: physical component score (PCS) and mental component score (MCS). The PCS is derived from the following domains , whereas the MCS is derived from emotional role, social function, mental health, and vitality domainsParticipants also completed the Beck Depression Inventory-II (BDI-II), a 21-item self-report questionnaire that assesses affective, cognitive, and somatic symptoms of depressionThe Pittsburgh Sleep Quality Index (PSQI) is the most commonly used tool for a comprehensive assessment of sleep qualityThe sample size determination was performed using the Spanish software Ene 3.0 . The calculations were based on detecting clinical differences of 10 points in the ODI and standard deviation of 13 pointsData were analyzed with the statistical package SPSS version 21.0 . Descriptive data were collected for all patients. The Kolmogorov-Smirnov test was used to analyze the normal distribution of the variables. Quantitative data without a normal distribution (BDI and MCS) were analyzed with nonparametric tests, and the remaining data with normal distribution were analyzed with parametric tests. Differences in the quantitative variables between countries were assessed with the unpaired Student-t test and the nonparametric Mann-Whitney U-test. The chi-square (χ2) test was used to analyze differences in sex between both groups. A 2-way analysis of variance (ANOVA) test was used to investigate the differences in outcomes with country (Brazil or Spain) and gender (men or women) as the between-subjects factors. The Pearson (r) test and Spearman’s rho (rs) test were used to determine the correlations between demographic and clinical variables in each country. The strength of the correlations was classified as weak (r from 0.1 to 0.3), moderate (r from 0.4 to 0.6), or strong (r from 0.7 to 1)No significant differences between patients of either country were observed for age (P=0.64), gender distribution , height (P=0.06), BMI (P=0.85), years with pain (P=0.74), pain intensity (P=0.24), PPI (P=0.92), PRI total score (P=0.72), or NWC (P=0.11). On the other hand, we found greater disability in Spanish patients than in Brazilian people , P=0.02). The ANOVA revealed a significant Country * Gender interaction for PRI total score (P=0.04), but not for intensity of pain (P=0.88), disability (P=0.35), PPI (P=0.75), or NWC (P=0.06). Spanish women with LBP exhibited greater pain ratio than Spanish men , whereas no gender differences were found in Brazilians. Significant differences between countries were observed for physical  but not for mental (P=0.31) component scores of the SF36 questionnaire: Spanish patients exhibited lower physical quality of life than Brazilian patients . When geNo significant differences between countries were observed for depressive symptoms (P=0.98) or sleep quality (P=0.94) . When geSignificant positive correlations were found between age and BMI, ODI, NPRS, PRI, and PPI in Brazilian, but not Spanish, patients with LBP. Within Brazilian patients, the older the patients were, the greater the BMI, disability, and pain intensity. Age was negatively associated with PCS in Brazilian, but not Spanish, patients. The older the patients were, the lower the physical component of quality of life  and 4.The Spanish group showed a consistent pattern of correlations for clinical data, where all variables were significantly related to each other, with a few exceptions including PSQI to PCS, NPRS to BDI and PCS, and PPI to PSQI. All correlation coefficients were considered moderate or high .In contrast, within Brazilian patients, the correlation pattern depended on the outcome. Thus, the ODI was the only variable related to all of the others, with the exception of the MCS: the greater the disability was, the worse the pain intensity, sleep, physical quality of life, and mood. The PCS also showed negative correlations with PRI, PPI, BDI, and MCS: the worse the physical aspect of quality of life, the worse pain intensity, mood, or sleep quality. In general, correlations within Brazilian patients were lower than those in the Spanish group .The results of the current study show that pain perception in patients with LBP can be affected in some aspects depending on the country of residence. We observed that the country of origin and gender do not determine a different pattern of behavior for physical quality of life and disability; however, the mental quality of life and mood of Spanish women suffering from LBP was appreciably worse than those of Brazilian men and women and Spanish men. Further, the correlation patterns seen in Spanish patients suggest that LBP could be a global phenomenon affecting several components of the subject’s life, whereas this correlation is less clear for Brazilians, at least for the studied sample.Pain intensity did not show significant differences between the two countries. In fact, differences in the NPRS did not achieve the threshold to be considered clinically relevantOur sample of Spanish patients reported a similar physical health-related quality of life status than in other countriesNo differences in depressive levels were observed between Brazilian and Spanish patients with LBP. The prevalence of depression in patients with LBP is high,In addition, Brazilian and Spanish patients with LBP exhibited similar patterns of sleep quality. In our study, most of the patients showed around 8 points suggesting that both populations exhibited poor sleep quality-It is well accepted that gender is a relevant factor in the modulation of pain, and there is a considerable body of evidence suggesting that women have more frequent LBP,,,In the current study, gender was a differentiating factor between countries in some outcomes. For instance, although the intensity of LBP and the NWS did not reveal differences by gender and country, Spanish women reported higher PRIWe observed that Spanish women reported worse mental, but not physical, health status than Brazilian women and Spanish men. These data are partly in agreement with those of other authors, in which Italian women also reported poorer mental and physical health,,Different theories are proposed to explain gender differences in pain perception. First, biological factors may interfere in the greater frequency of chronic pain in women,We tried to determine the potential global self-perception of the condition by investigating the correlation between different outcomes. We found several correlations within Spanish patients with LBP that were less significant in Brazilian people. These findings indicate that LBP seems to be considered a global condition by Spanish people with several domains affected to the same extent, as previously describedAccording to our results, when dealing with LBP it seems necessary to include the social and cultural aspects in the clinical context since this may offer an improvement in the therapeutic approach and the long-term clinical results.We should recognize some potential limitations in the current study. First, the sample size can be considered small, which could decrease the power of multiple comparisons; however, our main objective was not to conduct a population-based study. Future studies including more representative populations are now needed to determine the influence of cultural factors on LBP. Secondly, the clinical heterogeneity of the patients could also influence the results. Further, social variables were neither collected nor studied, which limits the applicability of the results. Third, we did not collect outcomes on catastrophism or kinesiophobia, two clinical topics relevant to patients with LBP. Finally, the questionnaires used in the study were not specific for LBP patients, with the exception of the ODI. Other questionnaires could afford new perspectives on the results.This study showed that pain perception in patients with LBP is affected in some aspects depending on the country of residence. We found that Spanish women reported greater pain index, poorer mental health, poorer mood, and a poorer quality of life than Spanish men and Brazilian patients. No differences in pain intensity and disability were observed. The level of relationships between pain, disability, quality of life, mood, and sleep patterns was significantly higher in Spanish patients with LBP, suggesting that this condition is considered a global entity affecting multidimensional contexts within Spanish patients. Future population-based studies are needed to determine the potential relevance of cultural factors in patients with LBP.