Introduction. Pain after cardiac surgery affects long-term patient wellness. This study investigated the effect of preoperative pregabalin on acute and chronic pain after elective cardiac surgery with median sternotomy. Methods. Prospective double blind study. 93 cardiac surgery patients were randomly assigned into three groups: Group 1 received placebo, Group 2 received oral pregabalin 75 mg, and Group 3 received oral pregabalin 150 mg. Data were collected 8 hours, 24 hours, and 3 months postoperatively. Results. Patients receiving pregabalin required fewer morphine boluses  and had lower pain scores at 8 hours  and 3 months  and lower morphine consumption at 8 hours  and 24 hours . Percentage of patients with sleep disturbances or requiring analgesics was lower in the pregabalin group and even lower with higher pregabalin dose  3 months after surgery. Conclusion. Preoperative oral pregabalin 75 or 150 mg reduces postoperative morphine requirements and acute and chronic pain after cardiac surgery. Acute postsurgical pain and the possible progression to chronic postsurgical pain (CPSP) can influence patients' immediate and late postoperative course after cardiac surgery . SourcesApproaches used in an attempt to reduce pain after cardiac surgery include local anesthetic infiltration of the sternotomy and chest tube insertion sites , parastePregabalin  is a beta-isobutyl of GABA with chemical similarity to gabapentin . PregabaPregabalin may have a role in controlling acute postoperative pain and published evidence suggests that it may be effective in prevention of chronic postsurgical pain (CPSP) , 26, 27.NCT01701921).After approval by the Ethics Committee, 93 patients scheduled for cardiac surgery in a tertiary care University Hospital enrolled in this double blind, placebo controlled, randomized study. The study protocol was in agreement with the Helsinki Declaration on patient safety during anesthesiology research  and was Inclusion criteria were elective primary cardiac surgery with median sternotomy and extracorporeal circulation, ages 18–85 years, and written informed consent for participation in the study. Exclusion criteria included previous cardiac or thoracic surgery, allergy to pregabalin, previous use of gabapentin or pregabalin, chronic pain, known diagnosis of depression or other major psychiatric diseases, cognitive impairment or inability to cooperate with the study, renal insufficiency, and history of substance abuse. Patient demographic and clinical data were stored in a secure, encrypted electronic database. Based on a computer custom number generator, patients were randomly assigned to one of three groups: Group 1 = control (patients received a placebo capsule), Group 2 = low dose pregabalin  , and patients in Group 3 = high dose pregabalin received a capsule containing 150 mg of pregabalin. The study drug  was given to patients by a research coordinator and was documented in the medical record as “study drug.” All anesthesia personnel taking care of patients in the operating room were blinded to group assignment.μg/kg/minute and remifentanil infusion 0.1–0.2 μg/kg/min, titrated to maintain BIS values in the 35 to 50 range, and sevoflurane was discontinued. All operations were performed by the same surgeon, through midline sternotomy, using cardiopulmonary bypass with a roller pump and membrane oxygenator; pump flow rate was approximately 2.5 L/min/m2 in order to maintain perfusion pressure around 50 mm Hg. During cardiopulmonary bypass, core temperature was normal for coronary artery bypass graft (CABG) procedures, while mild hypothermia was applied for valve replacement operations. At the end of surgery, patients remained intubated and were transported to the ICU under continuing propofol and remifentanil infusion for sedation. Criteria for weaning from the ventilator and extubation were hemodynamic stability, absence of excessive chest tube drainage or arrhythmias, normothermia, adequate urine output, spontaneous ventilatory frequency < 20 breaths/min, and a cooperative patient that could respond to basic commands. After extubation, when patient condition was satisfactory, patients received a single 5 mg dose of intravenous morphine and patient control analgesia (PCA) was started with a programmable PCA pump  using the following settings: basal morphine infusion 0.5 mg/hour, bolus dose 0.5 mg, and lockout time 30 minutes. Analgesia was supplemented with IV paracetamol 1 gm every 8 hours for the first 24 hours after surgery. In addition, if the analgesic regimen was not sufficient despite maximum PCA use, we advised ICU clinicians to provide additional (rescue) analgesia with IV morphine as deemed necessary. The goal was to keep pain scores measured by Verbal Rating Scale (VRS) (0 = no pain to 10 = unbearable pain) at rest ≤ 4 for every patient. An anesthesiologist blinded to group assignment visited the patients in 8 hours and 24 hours after extubation, recorded VRS after a deep breath, documented the presence and severity of nausea and vomiting, and collected data on PCA use and morphine consumption from the Gemstar pump. In addition, a blinded searcher interviewed all patients by telephone 3 months after surgery, inquired about the impact of the operation on their lives, and asked specific questions about the presence and severity of pain after surgery. In cases where patients indicated they were still experiencing pain, the researcher also collected data about use of analgesics and the presence of sleep disorders.After introduction of a large intravenous catheter in the upper extremity and placement of standard monitoring  the radial artery was cannulated under local anesthesia. Then, a bispectral index (BIS) sensor was placed, general anesthesia was induced using etomidate 0.3 mg/kg and fentanyl 30 mcg/kg, and intubation was facilitated with vecuronium 0.1 mg/kg. Anesthesia was initially maintained using sevoflurane at 1–1.2 age-adjusted MAC until insertion of a cordis in the right internal jugular vein and placement of a continuous cardiac output/mixed venous oximetry pulmonary artery catheter. Then, after central line placement was completed, anesthesia was maintained using propofol 100–200 Sample size calculation was based on assumptions supported by the findings of an earlier pilot, unpublished study, as follows: primary outcome is morphine consumption at 24 hours, morphine consumption at 24 hours is mean = 20 mg, with SD = 5 mg, and a change of morphine use by 4 mg is a clinically meaningful change. Using these assumptions, the required sample size to have alpha error = 0.05 and power = 0.8 is 26 patients per group. Based on this calculation, we decided to increase sample size by 20% to 32 patients per group, in order to reduce the risk of not having adequate sample size due to patient attrition, missing data, errors in patient allocation, or other study shortcomings. t-test or the Mann–Whitney test was used for post hoc testing, to ascertain which pair of groups had significantly different values.Normality of continuous data was assessed with the Kolmogorov-Smirnov and Shapiro-Wilk tests, and findings regarding normality were visually validated with normal Q-to-Q plots and detrended normal Q-to-Q plots. Based on this analysis, data on age, weight, height, BMI, and operation times were analyzed using ANOVA, whereas all other continuous variables were analyzed using the nonparametric Kruskal-Wallis test. When ANOVA or Kruskal-Wallis test showed a significant difference between groups for a particular variable, Student'sp values for significance using the Bonferroni method, by dividing 0.05 by the number of comparisons [p value for significance was adjusted to 0.05/20 = 0.0025 for the demographic and comorbidity variables presented in p values < 0.0025 or 0.0042, respectively, were considered significant. The Statistical Package for Social Sciences  was used for data analysis.Frequencies for binary (yes/no) variables such as hypertension, arrhythmia, vomiting in the first 24 hours, use of analgesics, or sleep disturbances after 3 months were compared between groups using the Chi-square test. Because of the high number of comparisons during data analysis, we adjusted parisons , 31. TheOf 108 eligible patients, 101 patients enrolled in the study, and 93 patients completed the study  as shown in the CONSORT diagram in p < 0.0025 (Bonferroni correction), only duration of surgery was significantly different between groups, being significantly shorter in Group 3 (p = 0.002).Patient age was (mean ± SD) 67.1 ± 8.3 years, weight was 80.7 ± 11.9 Kg, height was 168 ± 7 cm, and BMI was 28.5 ± 3, while median ASA physical status was 3 (range 3-4). Frequency of comorbidities and medication use initially seemed significantly different between groups for several variables. However, after adjusting the significance level to 0.05/20, therefore p values for significance were adjusted to 0.0042 using the Bonferroni correction, as described in Methods in order to avoid false positive findings due to multiple comparisons. Differences between groups remained significant for most variables of interest even after adjusting p value for significance to 0.0042: the number of morphine dose requests and doses given, total morphine use in the first 8 hours and the first 24 hours, pain scores at 8 hours and at 3 months, and the frequency of sleep disturbances at 3 months were significantly different between the three groups.Data on analgesic use, adverse effects, acute postoperative pain, chronic pain, and sleep disturbances are presented in When the overall testing showed a significant difference between groups for a variable of interest, as presented in With regard to vomiting, which can be very distressing for patients, there was no significant difference between groups. However, further analysis showed that morphine consumption at 8 and at 24 hours and pain scores at 8 hours and at 3 months were significantly higher in patients who experienced vomiting compared to those who did not .Our results suggest that a single dose of pregabalin can result in a small but potentially beneficial reduction of acute postoperative pain and opioid consumption in the immediate postoperative period and may also reduce chronic poststernotomy pain in patients undergoing elective cardiac surgery with median sternotomy and use of cardiopulmonary bypass. Pregabalin, when added to the analgesic effect of morphine results in lower analgesia needs in the elderly, thereby leading to less severe acute postoperative pain and may potentially halt the progression to chronic pain, in accordance with the concept of “preventive analgesia” , 33.Pregabalin has been used in different types of surgery and published clinical studies suggest that chronic pain may be reduced in patients who receive perioperative pregabalin , 26, butConsidering the age of our patients  we chose to only use a single dose of pregabalin (75 mg or 150 mg) in our study, in an attempt to minimize adverse effects in these elderly patients. Because the risk of confusion is high after cardiac surgery with cardiopulmonary bypass due to various mechanisms, including hypoperfusion, microemboli, and fast rewarming , we chosAnalysis of VRS in the first 8 hours after extubation showed significant difference between Groups 1 and 2 and Groups 1 and 3. After 24 hours the difference between Groups 1 and 2 is not significant, possibly because any difference is masked by increased morphine dose, but there is still significant difference between Groups 1 and 3. No difference is detected between Groups 2 and 3 at 8 and 24 hours. The above findings imply that a higher pregabalin dose is associated with less severe pain.However, it is important to note that because the observed “average” differences in pain scores between groups were small, the clinical significance of such differences can be questioned. Similarly, the observed benefit with regard to reduced morphine consumption in the pregabalin groups is also small. Yet, we believe that the observed benefits with regard to pain scores and with regard to morphine consumption are clinically meaningful: differences in “maximum” scores are larger (2 points in most cases), and maximum pain is important from the viewpoint of patient experience. Similarly, maximum doses of morphine are markedly lower in patients who received pregabalin, and this reduction could be beneficial with regard to patient recovery and rehabilitation. Furthermore, it would not be realistic to expect a big, dramatic benefit from a single intervention in a complex, multifactorial care process, such as in cardiac surgery. Given the complexity of these cases, we believe that even a small reduction in pain intensity is a meaningful improvement as we all try to improve care for these patients. Three months after surgery the pattern is almost the same with patients in Group 1 experiencing more severe postoperative pain, using more analgesics and experiencing more sleep disturbances compared to patients in the pregabalin groups.Although the small number of patients is a significant limitation of our study, the observed small but significant findings and the fact that these findings are biologically plausible and consistent with principles currently accepted in the pain literature support the validity of our findings. The observed significant difference in duration of surgery between groups, though statistically significant, is, in our opinion, of no clinical consequence and is unlikely to influence postoperative pain or any other relevant outcomes.In conclusion, our data suggest that a single preoperative dose of oral pregabalin has small but potentially significant opioid-sparing effect, resulting in small but measurable improvement of postoperative pain with reduced morphine consumption and lower pain scores in the immediate postoperative period. The observed benefits with regard to opioid use and pain scores are small but clinically relevant, in our opinion, and may result, possibly through blockade of central sensitization mechanisms, in reduced long-term pain, with lower pain scores and fewer sleep disturbances 3 months after elective cardiac surgery. We believe that these results are truly promising. However, because this is a small, single center study and the observed clinical benefits are small, additional large, well conducted studies in different patient populations are needed to critically evaluate the validity of our findings.


Migraine is a common cause of emergency department (ED) visits. To date, there is no recommended drug of choice for pain management of these patients. In the present study, we aimed to evaluate the effectiveness of ketorolac and magnesium sulfate in this regard.This is a cross-sectional study performed on all 18 - 60 year-old patients, visiting two different EDs with complaint of moderate to severe migraine headache. Patients were treated with 30 mg ketorolac in one hospital and 1 gram magnesium sulfate in the other. Pain scores were assessed on arrival, 1 and 2 hours after drugs administration and quality of pain management was compared between two groups using SPSS 22. 70 patients with the mean age of 36.4 ± 11.4 years were enrolled . The two groups were similar regarding baseline characteristics (p > 0.05). The improvement in pain score in magnesium sulfate group was greater than Ketorolac group after both one hour  and two hours .It seems that both ketorolac and magnesium sulfate are significantly effective in pain control of patients with migraine headache presenting to the emergency department. Magnesium sulfate was superior to ketorolac both one and two hours after drug administration. Migraine is a disabling disorder and a common cause of emergency department (ED) visits , 2. MigrIn the present study, we aimed to evaluate the effectiveness of ketorolac and magnesium sulfate in controlling migraine headaches in patients presented to ED.Study design and settingThis is a cross-sectional study performed from April to October 2015 in emergency departments of Imam Hossein and Shohadaye Tajrish Hospitals, Tehran, Iran, to compare the effectiveness of ketorolac and magnesium sulfate in migraine pain management. Ethical issuesThe protocol of the study was approved by the Ethical Committee of Shahid Beheshti University of Medical Sciences. The authors declare their adherence to ethical principles of Helsinki Declaration throughout this research. Eligible patients were enrolled after signing informed consent form. ParticipantAll 18 - 60 year-old patients, visiting the emergency department with complaint of moderate to severe headache were interviewed by the main investigators. They were included if compatible with the international headache society (IHS) criteria for common migraine and had a pain score more than 5 ). Patients with history of peptic ulcer disease, ischemic heart disease, inflammatory bowel disease, coagulopathy, renal or hepatic failure, history of recent major surgery, history of hypersensitivity to the studied drug, and hypertension, as well as pregnant or breastfeeding women were excluded.Studied groupsPatients in Shohadaye Tajrish Hospital were treated with 30 milligrams ketorolac and those in Imam Hossein Hospital with 1 gram magnesium sulfate. One of the investigators in each hospital assessed pain scores on arrival, 1 and 2 hours after drug administration, when plasma concentration reaches its peak level. Patients, pain investigator, and data analyzer were blind to the administered treatment. 3 or more scores decrease in VAS was considered as clinically significant pain management.Statistical analysisStatistical analysis was performed using SPSS version 22. Continuous variables were described as mean ± standard deviation, and categorical ones as median, interquartile range, frequency and percentage. Mann-Whitney U test and Wilcoxon test were used to analyze differences in VAS pain scores. P value < 0.05 was considered significant. Seventy patients with the mean age of 36.4 ± 11.4 years were enrolled . Baseline characteristics of patients in each group, as well as their VAS scores at baseline, 1 hour, and 2 hours after drug administration are compared in table and Based on data extracted from the current study, both ketorolac and magnesium sulfate are significantly effective in pain control of patients with migraine headache presenting to the ED. Magnesium sulfate was superior to ketorolac one and also two hours after drug administration. These drugs have been studied in patients with migraine headache solely or in comparison with other drugs. However, searching in Google Scholar and Pubmed database with “ketorolac and magnesium sulfate and migraine” as keywords, did not find any article that compared these two with each other. The findings of the literature have yielded conflicting results. A paper review performed in 2000 on the effectiveness and safety of different therapies in migraine headache, revealed that magnesium sulfate needs to be studied in appropriate trials before a conclusions can be drawn. Ketorolac performs a little better but has been shown to be inferior to other treatments . 15 yearIt seems that both ketorolac and magnesium sulfate are significantly effective in pain control of patients with migraine headache presenting to the emergency department. Magnesium sulfate was superior to ketorolac both one and two hours after drug administration.


Temporomandibular disorder (TMD) is described as a subgroup of orofacial pain with a set of signs and symptoms that involve the temporomandibular joint, masticatory muscles, ears, and neck. TMD can occur unilaterally or bilaterally and approximately 70% of the population is affected with at least one sign. The disorder progresses with orofacial pain, muscle pain involving the masticatory and cervical muscles, joint noises (clicks and pops), joint block, mandibular dysfunction, and headache. The etiology can be abnormal occlusion and/or posture, trauma involving local tissues, repetitive microtrauma, parafunctional habits, and an increase in emotional stress. Studies have demonstrated that phototherapy is an efficient option for the treatment of TMD, leading to improvements in pain and orofacial function.The aim of the proposed study is to compare the effects of two sources of photobiomodulation in individuals with TMD. A randomized, controlled, double-blind, clinical trial is proposed, which will involve 80 individuals aged 18–65 years allocated to either a laser group or light-emitting diode (LED) group submitted to 12 sessions of phototherapy. The Research Diagnostic Criteria for TMDs will be used to evaluate all participants. Pain will be measured using the visual analog scale and maximum vertical mandibular movement will be determined with the aid of digital calipers.This study compares the effects of two modalities of laser therapy on the pain and orofacial function of patients with TMD dysfunction. Photobiomodulation and LED therapy are treatment options for reducing the inflammatory process and pain as well as inducing the regeneration of the target tissue.NCT03257748. Registered on 8 August 2017.ClinicalTrials.gov, The online version of this article (doi:10.1186/s13063-018-2444-7) contains supplementary material, which is available to authorized users. The temporomandibular joints link the lower jaw (mandible) to the temporal bone of the skull, which is immediately in front of the ear on each side of the head. The flexibility of the joints allows the mandible to move up and down as well as from side to side , 2.Temporomandibular disorder (TMD) is described as a subgroup of orofacial pain with a set of signs and symptoms that involve the temporomandibular joint, masticatory muscles, ears, and neck either unilaterally or bilaterally –6. The sDue to the pain and functional limitations inherent to TMD, phototherapy has been investigated and has proven to be an important treatment option for this disorder , 16, 17.Drugs are widely employed for the treatment of pain, but are expensive, which generates high costs in the public health realm, and have limited effectiveness as well as potentially serious side effects, especially when administered for prolonged periods of time. Thus, non-pharmacological, non-invasive resources for pain relief are of the utmost importance and have been widely investigated in the scientific literature.Based on previous studies conducted by different research groups, the proposed study will test the hypothesis that photobiomodulation in the form of low intensity laser compared to LED decreases pain and improves temporomandibular joint function, thereby accelerating the return to activities of daily living.The aim of the proposed study is to analyze the effect of laser therapy and LED therapy on pain and function in patients with TMD and its association with neck pain.At the end of the study, we expect to find a reduction in pain in the temporomandibular joint and temporal muscle region, and improvement in the function of the temporomandibular joint through photobiomodulation and LED therapy in patients with TMD, with a consequent improvement in their quality of life.This protocol is presented in accordance with the 2013 SPIRIT  Statement  will be selected to participate in the study. No restrictions will be imposed with regard to race.The volunteers will be informed of all procedures and sign a statement of informed consent before the onset of the study.Clinical diagnosis of TMD, separated by the degrees of this function based on the Research Diagnosis Criteria for Temporomandibular Disorders, as shown in Table Age 18–65 years;Presence of at least 20 functional teeth, at least three being molars.Dentofacial anomalies;Currently in orthodontic or orthopedic treatment for the jaw;Currently undergoing psychological treatment;Use of muscle relaxant or anti-inflammatory agent.p < 0.05), and 80% test power. The sample was determined to be 80 individuals, who will be allocated to two groups.Step 1 – Recruitment for the selection of patients who will participate in the study. The patients will receive clarifications regarding the objectives and procedures and those who agree to participate voluntarily will sign a statement of informed consent.Step 2 – The selected patients will receive an envelope containing a card stipulating to which group they will be allocated. The patients will not be aware of the content of the envelope.The sample size was calculated based on studies found in the literature using maximum vertical mandibular movement as the basis, with a standard deviation of 9.82, a 5% significance level  will be submitted to eight sessions of phototherapy held twice a week for four weeks, during which only the researcher in charge of programming the phototherapy device will be aware of which treatment is being employed. However, the programmer will not participate in the execution of the treatments, evaluations, or data analysis.Temporomandibular joint region: around the temporomandibular joint;Masseter and temporal muscles: on the masseter and the anterior temporal.Phototherapy will be applied:The number of irradiated points will depend on the treatment. Patients in the laser group will have three points irradiated, while those in the LED group will have 36 points irradiated. The parameters that shall be used can be found in Table The initial evaluations will be performed by an examiner who will be duly trained by a “gold standard” evaluator following an evaluation protocol. To confer greater reliability to the results, the examiner will be blinded to the allocation of the participants to the different groups. A second examiner will perform the re-evaluations following the treatment protocols and will also be blinded to the allocation of the participants. This examiner will also be duly trained following the evaluation protocol.Research Diagnostic Criteria for Temporomandibular Disorders (RDC/TMD): Potentially eligible patients will be diagnosed using the RDC/TMD, which consists of a clinical exam involving the palpation of the temporomandibular joints an analysis of the mandible with the aid of digital calipers to measure vertical and horizontal movements and a stethoscope to evaluate joint sounds. Symptoms such as headache, fatigue and difficulty when chewing, bruxism, psychological state, and parafunctional habits will then be investigated.Visual analog scale: This scale will be used for the assessment of pain and consists of a 10-cm line with 0 (absence of pain) printed at one end and 10 (debilitating pain) printed at the other end. The participants will be asked to mark a place on the line that represents their current pain intensity. The researcher will subsequently use a ruler to register the distance from zero to obtain a numeric representation of the pain level. These procedures will be performed before and after treatment.Maximum vertical mandibular movement: The volunteer will be instructed to open his/her mouth a wide as possible. Maximum vertical mandibular movement will be measured as the distance between the maxillary and mandibular central incisors determined with the aid of digital calipers. The volunteer will then be instructed to exert pressure on the mandibular teeth with the mouth open and move the mandible to the right and left for the determination of excursion (distance between upper and lower mid points). These procedures will be performed before and after treatment.p < 0.05).The results will be tested for normality using the Kolmogorov–Smirnov test. Parametric data will be submitted to analysis of variance (ANOVA) with the Tukey–Kramer post hoc test. Non-parametric data will be submitted to Friedman’s test. The level of significance will be set to 5% (Phototherapy has been employed for 30 years and there are no reports of side effects in the literature.The following are the expected benefits: reductions in signs of inflammation, pain and muscle tension of the masticatory, and cervical muscles as well as an improvement in orofacial function, enabling greater mobility and functionality of the temporomandibular joints.Pain and functional limitations are inherent to temporomandibular dysfunction, and studies indicate that 70% of the population is affected with at least one TMD signal –16. MediPhototherapy has the potential to reduce pain and improve temporomandibular joint function in TMD patients, with consequent improvement in their quality of life. Photobiomodulation and LED therapy are treatment options for reduction of the inflammatory process and pain, besides inducing the regeneration of the target tissue –20.The efficacy of phototherapy for the treatment of TMD has been proven by several authors , 11, 17,This study is currently recruiting participants.


Neuropathic pain is clinically described as pain caused by a lesion or disease of the somatosensory nervous system. The aim of this study was to assess the validity of the Dutch version of the DN4, in a cross-sectional multicentre design, as a screening tool for detecting a neuropathic pain component in a large consecutive, not pre-stratified on basis of the target outcome, population of patients with chronic pain. Patients’ pain was classified by two independent (pain-)physicians as the gold standard. The analysis was initially performed on the outcomes of those patients (n = 228 out of 291) in whom both physicians agreed in their pain classification. Compared to the gold standard the DN4 had a sensitivity of 75% and specificity of 76%. The DN4-symptoms (seven interview items) solely resulted in a sensitivity of 70% and a specificity of 67%. For the DN4-signs (three examination items) it was respectively 75% and 75%. In conclusion, because it seems that the DN4 helps to identify a neuropathic pain component in a consecutive population of patients with chronic pain in a moderate way, a comprehensive  examination by the physician is still obligate. Neuropathic pain is described as pain caused by a lesion or disease of the somatosensory nervous system and requires a demonstrable lesion or a disease that satisfies established neurological diagnostic criteria. MoreoveSince current pharmacological treatment of patients with and without a NePC differs strongly, a correct pain classification is imperative, 10. TheThe original French validation study of the ‘Douleur Neuropathique en 4 Questions’ (DN4) was perfThe neuropathic pain special interest group (NeuPSIG) grading system is develThe aim of this study was to assess the validity and reliability of the DN4 as a screening tool for use in daily outpatient practices to detect a NePC in a, not pre-stratified on the target outcome, consecutive patient population having chronic pain syndromes due to low back and leg pain (LBLP), neck-shoulder-arm-pain (NSAP) or pain of suspected neuropathic origin (PSNO).This validity and reliability study had a cross-sectional, longitudinal, research design with a 2-weeks and 3-months follow-up period. Comparisons were made between the DN4 (as a whole and for the symptom questions and signs tests separately) and the classification of patients’ pain by two, independently working, physicians (the gold standard) as well as with the grading system.The study was approved by the Committee on Research Involving Human Subjects region Arnhem-Nijmegen, Nijmegen, the Netherlands,  which counts for participation of the Dutch academic pain centers , Dutch non-academic pain centers  and a Dutch non-academic department of neurology . Participation of Dutch non-academic pain center in Delft, the Netherlands (Reinier de Graaf gasthuis) was approved by Medisch Ethische Toestings Commissie Zuidwest Holland (dossier number: 10–145). The study protocol was registered in the Dutch National Trial Register (NTR3030).DETECT .We used the same methodology as in the published protocol  and as eConsecutive patients (first time visitors of the participating centers) without pre-stratification based on the target outcome were incAt that time, there was only a rough diagnosis: LBLP, NSAP or PSNO. Inclusion criteria: Male and female adult patients (≥18 years of age) with chronic (≥3 months) LBLP or NSAP radiating into respectively leg(s) or arm(s) or patients with chronic pain due to a PSNO . Exclusion criteria: Patients diagnosed with malignancy; compression fractures; patients with diffuse pains ; severe mental illness; chronic alcoholism or substance abuse; inability to fill in the questionnaire adequately or incapable of understanding the Dutch language.The physicians  participating in this study were not selected on basis of age, experience as a physician or any other criteria. Classification of patients’ pain was based on the NeuPSIG guidelines on neuropathic pain assessment and recoIn this study, 62 physicians  participated. The physicians who were classifying patients’ pain at the first session were called ‘Physicians A’. The physicians who performed the classification at the second session, were called ‘Physicians B’.The DN4 , 20, 25 The items of the DN4 are scored based on a yes (1 point) /no (0 points) answer. This leads to a score range of 0–10 when the symptoms (range 0–7 points) as well as the signs (range 0–3 points) items are included. Values in the DN4 who were not filled in were considered as ‘no’ (0 points). However, in the reliability analysis these data were not incorporated.The Patients Global Impression of Change (PGIC), 45–47 wAll baseline measurements  took place on preferably the same day. The PGIC –47 and tAll data was collected on paper and stored by Radboudumc, Nijmegen, The Netherlands. Data management and monitoring were performed within MACRO . Data analysis and statistics was performed by use of Statistical Package for the Social Sciences .According to the power-calculation in the protocol 132 patients with LBLP, NSAP or PSNO were needed such that the sample size contains adequate numbers of cases and controls. QualitaThe agreement between any of the two combinations of the two observers (pain classification by the physician and the outcome of the grading system) to establish a present NePC or absent NePC, and of the DN4 (DN4 / DN4-symptoms / DN4-signs outcome) was evaluated by use of Cohen’s kappa (K), prevalence index (Pi) and percentage of pair wise agreement (PA). The categorization of the kappa values are, according to the categorization of observer agreement by Landis and Koch, none beBased on the classifications of the two physicians, all patients were categorized as absent NePC, present NePC or ‘undetermined’ (i.e. the pain classification of the two physicians was not the same).2-test . The statistical significant differences between present NePC, absent NePC and the Undetermined group was assessed by use of One-way ANOVA  or Kruskal-Wallis test. Chi2 test was also used to analyze the nominal outcome scale of the DN4 regarding the three groups.Statistical significant differences between absent NePC and present NePC were determined by use of students t-test , Mann-Whitney U-test groups  or via ChiA factor analysis was used to study the structure of the DN4 in such a way that variables that were thought to reflect a smaller number of underlying variables were observed. This method was performed for all three versions of the DN4 . Principal axis factoring was used as the extraction method. The varimax rotation with Kaiser normalization was used. Extraction of the factors was based on Eigenvalues being greater than 1.0. Cronbach’s alpha was used to calculate the internal consistency of the factors constructed. The results are only shown for the Physicians A (the assessment of the patient by the first physician). The outcomes by the Physicians B (the assessment of the patient by the second physician) are shown in A receiver operating characteristic (ROC) curve was calculated for the DN4 and the DN4 signs by both the physicians A and B and for the DN4-symptoms as filled in by the patient. The area under the curve (AUC) with 95% confidence interval was presented to indicate the discriminatory power of the DN4 to discriminate patients by present NePC or absent NePC. This dichotomy was based on the physicians’ assessment outcome or based on the grading system outcome, respectively. The theoretical maximum of the AUC is 100%, indicating a perfect discrimination and 50% is equal to tossing a coin. An AUC between 0.9 and 1 is considered to be excellent, an AUC between 0.8 and 0.9 is good and between 0.7 and 0.8 is fair. An AUC between 0.6 and 0.7 is considered to be poor. Between 0.5 and 0.6 the AUC is considered to be failed–52. The Clinimetrics of the DN4 based on both the physicians assessment and/or both the grading system outcome were assessed for the DN4, the DN4-symptoms and for the DN4-signs items. A screening tool for the presence of a NePC is considered valid if it has a high sensitivity, specificity, high positive predictive value and a high positive likelihood ratio .Intraclass correlation (ICC) was used to assess reproducibility (‘test-retest reliability’) of the DN4-symptoms between the predetermined time points (baseline versus two weeks & baseline versus three months). Based on the guidelines by Cicchetti et al., 55 an ITwo-tailed p-value below 0.05 was considered statistically significant.In this study 330 consecutive patients were assessed for eligibility . Of thesClinical and social-demographic details of the 291 patients were analyzed based on their pain classification. No statistically significant differences were found between present NePC and absent NePC for gender, age, height, weight, BMI, medication and duration of pain. Also no statistically significant difference was observed between absent NePC and present NePC regarding current- worst and average pain .The proportion of agreement after chance agreement is removed  for the classification of patients’ pain (absent NePC or present NePC) by the physicians was 0.49 (moderate), with a PA of 78.4% . For the classification of patients’ pain on basis of the grading system K was 0.63 (good) and PA was 82% . The outcome of K and PA regarding the DN4 compared to the outcome of the assessment by physicians A was respectively 0.34 (fair) and 69.8% . Compared to the outcome of the assessment by physicians B it was 0.33 (fair) and 69.2% . Comparing the outcome of the DN4 to the outcome of the grading system, it was 0.35 (fair) and 69.1% for physicians A, and 0.32 (fair) and 67.3% for physicians B . The intIn 253 patients all the six outcome variables , the pain was classified as present NePC in all outcomes and in 22 patients (8.7%) it was six times negative, indicating absent NePC, so the agreement on all the six measures was 41.5% (the percentage of agreement based on both the gold standards and both the grading systems only was 56.9%).2) with the classification by the physicians , p<0.05. The descriptors ‘painful cold’ (p = 0.210) and ‘itching’ (p = 0.409) were not associated with the outcome of the classification. The DN4-signs (examination items) hypoesthesia to touch, pricking and brushing were statistically significant associated (Chi2) with the classification by the physicians , p<0.05.The DN4-symptoms (pain descriptors) burning, electric shocks, tingling, pins and needles, and numbness were statistically significant associated , between present NePC and undetermined (P<0.001) and between absent NePC and undetermined (P<0.001). In We constructed ROC-curves for the DN4, the DN4-symptoms and the DN4-signs with respect to the classification by physician A or B and according to the neuropathic pain grading system by physician A or B and all the combinations . This because of the chosen gold standard and the grading system in which patients were classified by two different physicians. This might have lead to differences in the outcomes relative to the individual outcome by the physician. In Based on the gold standard the sensitivity of the DN4 was on average  75% (95% CI 0.68–0.81), specificity 76% (95% CI 0.61–0.86), positive predictive value 92% and the positive likelihood ratio was 3.09 (95% CI 1.82–5.39) . For patIn Stability and responsiveness of the DN4-symptoms over time was assessed over a period of two weeks. The median sum score (IQR) of the DN4 at baseline for the total group was 3 (2–4), after two weeks it was 3 (2–4). Taking into consideration the fact that patients’ pain should not have changed (outcome based on the PGIC) because otherwise the ICC would not reflect the consistency of the DN4, test-retest reliability via ICC was 0.84 (excellent) . For the time gap of 7–21 days (to rule out the early or delayed return of questionnaires) between the first and second DN4-symptoms the ICC was 0.85 (excellent) . After three months, with no change in patients pain and a time gap of 60–120 days between the first and third DN4-symptoms, ICC was 0.79 (excellent) .The DN4 seems, in this study, to help to identify a neuropathic pain component in a consecutive population of patients with chronic pain in a moderate way.We used the concordant opinion about the classification of patients’ pain by two physicians as the gold standard. It is disputable if the term gold standard is practicable. However, as written by Versi 57] “th “th57] “To quantify the screening ability of the DN4, for the existence of a NePC, sensitivity and specificity can be used. HoweverAs a second comparison, we validated the DN4 in comparison with the grading system 21]. In. In21]. Bouhassira  presenteThere are several strengths in this study. At first, this study reflects daily clinical practice. In this study, we included a large cohort of patients irrespective of the predominant origin of the pain and level of pain which corresponds to a typical daily clinical patient population. These patients were associated with the most common specified medical conditions for pain (i.e. LBLP or NSAP or PSNO) and classified by two, independently working, physicians. Moreover, patients were referred from primary care to secondary and tertiary pain clinics and were assessed for their complaints for the first time at the time of inclusion in this study. This limits the risk of systematic bias and also reflects daily clinical practice. Secondly, we used a standardized assessment form in which the bedside examination and the grading system, 33 and Validation of screening tools should be performed in a standardized manner and described in detail, but performed in a setting which is comparable to a daily clinical practice. A research setting might be different from a clinical setting and thus might have influence on the patient and on the study results. The group of patients as well as the physicians under study should be comparable to the patients/physicians for who the tool is intended. Pre-stratification on the target outcome must be avoided , because this will lead to a non-clinical situation and thus decreases the validity and generalizability of the instrument, 71.The validity of DN4-signs is equal to the DN4 outcome and, importantly, both are more valid than the DN4-symptoms alone. It seems that the patients’ symptoms and signs doesn’t reliably reflect the underlying mechanisms, indicating there is a need for a more objective way to assess patients’ pain to facilitate improvement in the treatment of patients with pain. The physicians’ assessment cannot be replaced by a screening tool as the DN4, but gives the physician a little hint towards the (non-)existence of neuropathic pain component.S1 Table(DOCX)Click here for additional data file.S2 TablePD-Q: PainDETECT questionnaire; Present NePC: Neuropathic pain component existing; Absent NePC: Neuropathic pain component not existing; AUC: Area under curve; Std.Error: Standard error; Asymp. Sig.: Asymptotic Significance; 95%CI: 95% confidence interval; Sens.: Sensitivity; Spec.: Specificity; +DV: Positive diagnostic value; -DV: Negative diagnostic value; +LR: Positive likelihood ratio; -LR: Negative likelihood ratio; P[Z+]: a-priori chance for the existence of a NePC; P[Z-]: a-priori chance for no existence of NePC; FPR: False positive ratio; FNR: False negative ratio; A: Physician A; B: Physician B; LBLP: Low back and leg pain; NSAP: Neck shoulder arm pain; PSNO: Pain of suspected neuropathic origin.(DOCX)Click here for additional data file.


Root canal preparation techniques may cause postoperative pain. The aim of the present study was to compare the intensity of postoperative pain after endodontic treatment using hand files, single file rotary (OneShape), and single file reciprocating (Reciproc) systems. In this single-blind, parallel-grouped randomized clinical trial a total of 150 healthy patients aged between 20 to 50 years old were diagnosed with symptomatic irreversible pulpitis of one maxillary or mandibular molars. The teeth were randomly assigned to three groups according to the root canal instrumentation technique: hand files (control), OneShape and Reciproc. Treatment was performed in a single visit by an endodontist. The severity of the postoperative pain was assessed by the visual analogue scale (VAS) after 6, 12, 24, 48 and 72 h. Data were analyzed using the Kruskal-Wallis and Mann-Whitney U tests. P<0.05). There was no significant difference in mean intensity of postoperative pain between Reciproc and OneShape at 5 time points (P>0.05). The patients in control group reported significantly higher mean postoperative pain intensity at 12, 24, 48, and 72 h compared to the patients in the two other groups (The instrumentation kinematics (single-file reciprocating or single-file rotary) had no impact on intensity of postoperative pain. Post-endodontic pain is an annoying experience for the patient, undermining the patient-clinician relationship . DespiteEven when the highest standards are followed, post-endodontic pain of mild (with a frequency of 10-30%) , 8 and set al. [Several etiologic factors are attributed to post-operative pain including a history of preoperative pain, defective canal debridement, hyper occlusion, periapical disease and extrusion of debris into the periapical tissue . Extrusiet al.  demonstrReciproc is a single-file NiTi system, which claims to achieve cleaning and shaping with only one file. In this system reciprocating motion is used in three files  that should be installed on an electronic motor . The files are made of M-wire alloy, which provide higher flexibility and higher resistance to cyclic fatigue, compared to conventional NiTi rotary files -22. OneSin vitro studies have assessed the debris extrusion in different systems [While several  systems -17, few  systems -27. Therα=0.05 and a power of 80% (β=0.02) the sample size was calculated to be 50 in each group.This was an active-controlled, single-blinded, parallel-grouped, randomized clinical trial that was carried out under the approval of the Ethics Committee of Zahedan University of Medical Sciences (Grant No.: 7198) and was registered online . Assuming Healthy patients aging between 20 to 50 years old with a pulpal status of symptomatic irreversible pulpitis for one maxillary or mandibular molar were treated in the Endodontic Department of Zahedan Dental School. A written consent was obtained before recruitment. Exclusion criteria comprised of previous endodontic treatment, a history of medicine intake including corticosteroids, opioids and nonsteroidal anti-inflammatory drugs (NSAIDs) in the past 12 h, pregnancy, complicated anatomy (curves greater than 25 degrees), calcifications, internal and external resorption, open apices, periodontal disease, swelling and abscess, presence of periapical lesions, sensitivity to percussion and lack of occlusal contact. Prior to treatment a list of information regarding age, gender, type of tooth, pulpal and periapical status, presence of periapical lesion and a history of previous treatment were gathered from each patient. score 0 , score 1  and score 3 . One clinician assessed the clinical and radiographic information in terms of eligibility and assigned a code to each eligible patient record. The codes were then randomly assigned to three treatment protocols using table of random numbers. The treatment protocol for each patient was placed in a sealed envelope and then the envelope was given to the operator. After working length determination, an endodontist would open the envelope to pick up the treatment procedure; in control group canal instrumentation was conducted using K-files, and in test groups root canal treatment was done with either OneShape )MicroMega, Besancon, France) files or Reciproc  system. A standard initial protocol was carried out in the three groups. Allocation was done by a second person and thus the clinician performing the root canal treatment and the patient were blinded. Clinical diagnosis of pulpal status was confirmed by a positive response on cold testing with ENDO-ICE frozen gas . A visual analogue scale (VAS) was explained to the patients and considering the 0-170 markings on the VAS ruler, the level of pain was scored as follows: via buccal infiltration in the maxilla and inferior alveolar nerve block and long buccal infiltration in the mandibular region. No patient required more than two cartridges of local anesthetic. Isolation was made using rubber dam and access cavity was prepared using round carbide and diamond cylindrical burs in a high-speed hand piece. Upon exposure of the pulp chamber, if hemorrhage was not noticed (indicating pulp necrosis), patients were excluded. The lengths of the canals were determined using an electronic apex locator  and then confirmed radiographically. The instrumentation sequence used during the treatments in each group followed the procedure recommended by the manufacturer.Teeth were anesthetized using two cartridges of 2% lidocaine with 1:80000 epinephrine  Group 1: OneShape files (25/0.06) were used at the manufactures recommended speed (350-450 rpm and 2.5 N/ cm torque) in pecking motion till reaching working length. For wide canals, OneShape Apical  was used.Group 2: R25 files (25/0.08) were used in narrow canals, and R40 files (40/0.06) were used in large canals. Three in-and-out motions were applied with stroke lengths not exceeding 3 mm in the cervical, middle, and apical thirds until attaining the established working length.Group 3 (control group): canals were prepared using stainless steel K-files up to size #25 in smaller and #40 in larger canals. A 0.5 or 1-mm incrementally reducing step-back technique was used to provide tapers of 5% and 10%, respectively depending on the size of the canal.Following instrumentation with the mentioned techniques the coronal chamber was flushed with 1 mL of 2.5% NaOCl, and agitated ultrasonically for 1 min per canal followed by irrigation with 5 mL 17% EDTA and agitated ultrasonically for 1 min to remove the smear layer. Afterward, irrigation was repeated with 5 mL of 2.5% NaOCl solution and the procedure was completed by irrigation with 5 mL saline solution. The canals were then dried using paper cones and obturated using lateral condensation of gutta percha and AH-26 sealer. The tooth was then temporarily sealed using Cavit .The patients were advised to on-demand use of a 400-mg dosage of Ibuprofen for pain control , 28.At the end of the session VAS questionnaires were handed out to the patients and they were asked to assign a number correlating to their post-treatment pain, with 0 representing no pain and 10 representing the most severe pain imaginable. These scores were marked in intervals of 6, 12, 24, 48 and 72 h following endodontic treatment.A separate analyzer, unaware of the treatment groups, made phone calls at the designated intervals and recorded the VAS scorings. The data were analyzed using the Kruskal-Wallis and Mann-Whitney U tests. A cut off point of 0.05 was set as the statistical significance.A total of 160 patients were included in this study. At the end 10 patients were excluded due to procedural errors; including overfilled canals; and fractured instruments or failure to return the VAS forms and statistical analysis was performed on the remaining 150 participants.P>0.05).P<0.05). The highest postoperative pain intensity was recorded in the early stage after the root canal treatment.The results showed that the intensity of patient’s pain had significantly decreased by 72 h in all groups (P<0.05). There was no significant difference in mean postoperative pain intensity between Reciproc and OneShape at the 5 assessed time points (P>0.05)  .The aim of this study was to compare the intensity of postoperative pain using two single-file rotary and reciprocation systems (Reciproc and OneShape files).Due to the subjective and multifactorial nature of pain, many difficulties may arise in both measuring the postoperative level of pain and in controlling the various confounding factors involved. In the present study, the VAS questionnaire was used to quantify pain and categorize it into mild, moderate and severe groups.By way of randomization, applying a rather large sample size and also implementing strict inclusion criteria the various confounding factors such as age, gender, preoperative pain, type of tooth, pulpal and periapical status, number of treatment visits , 29 wereThe results of this study found no significant difference in post-operative pain between OneShape and Reciproc groups; however, the control group exhibited significantly higher pain intensity compared with the patients in the two other groups. This finding may be attributed to the Archimedes’ screw effect, which minimizes debris extrusion from the apical foramen -32. ThesIt is well established that extrusion of debris into the periapical region may irritate the periradicular tissues and cause inflammation leading to postoperative pain and flare-ups , 36. Whiet al. [vs. 50 in each group), periapical condition , preoperative pain categorize on the VAS (severe vs moderate), type of teeth (mandibular molars vs. mandibular and maxillary molars), number of teeth requiring root canal , sealer and obturation technique , Micro-computed tomography (µCT) studies have shown that reciprocating motion provides better shaping, with less incidence of canal transportation, compared to rotary files [Our study, however, has found no significant difference in terms of postoperative pain between reciprocating (Reciproc) and full-sequence rotary files (OneShape). In a randomized multicenter clinical study, Neelakantan et al.  reportedry files . OneShapry files . This coThis study found significantly higher levels of post-operative pain in the control group using K-files compared to Reciproc and OneShape groups. No significant difference was found between Reciproc and OneShape groups in terms of pain after endodontic treatment. It seems that the instrumentation kinematics had no impact on intensity of postoperative pain.


Clinical experience teaches us that patients are willing to accept postoperative pain, despite high pain intensity scores. Nevertheless, relationships between pain scores and other methods of pain assessment, e.g. acceptability of pain or its interference with physical functioning, are not fully established. Our aims were to examine these relationships.A cross-sectional study was conducted on patients who underwent major surgery between January 2008 and August 2013. Using logistic regression, we quantified the relationships between movement-evoked pain scores on the numerical rating scale (NRS-MEP) and three dichotomous dependent variables: patient’s opinion on acceptability of pain (PO: acceptable or unacceptable pain); nurses’ observation of patient’s performance of necessary activities to expedite recovery (NO: good or bad performance); a compound measure judging the presence of the clinically desirable situation of acceptable pain associated with good patients’ performance (PONO: present or not). Using Receiver Operating Characteristics (ROC) analysis, NRS cut-off points were determined such that they best discriminate between patients having one versus the other outcome for PO, NO and PONO.15,394 assessments were obtained in 9,082 patients in the first three postoperative days. Nine percent of the patients had unacceptable pain while having an NRS-MEP of 0–4. An estimated 47% (95%CI = 45%-49%) of patients with an NRS-MEP of 7 described their pain as acceptable on day one. Moreover, 33% (31%-35%) performed all required physical activities, and 22% (21%-24%) combined acceptable pain with appropriate movement. NRS cut-off points for PO, NO and PONO were five, four and four, respectively, but had insufficient discriminatory power.Our results suggest pain management should be guided by the many dimensions of the patient’s pain experience, not solely by NRS cut-off points. Future research should evaluate the impact of such multidimensional pain assessment on patients’ functional outcome. Many patients experience acute postoperative pain after major as well as minor surgery , 2. ClinMost of these assessment methods rely on the perception of pain and pain- related phenomena by either the patient or a professional caregiver , 4. SelfThe numerical rating scale (NRS), a validated instrument to assess pain intensity by self-reporting, is widely used for assessing pain on a scale from zero  to 10 (worst possible pain). Certain NRS scores have even been used as cut-off points to guide initiation or cessation of treatment in an individual or even as indicator of the quality of pain management in a population –10.Relationships between NRS and other methods of pain assessment, e.g. acceptability of the pain or its interference with physical functioning, are not fully established. In the clinical setting, some patients report a high movement-evoked pain score, yet claim that their pain is acceptable to them . Patientfirst, to quantify relationships between NRS and other methods of pain assessment and second, to examine the ability of an NRS cut-off point to predict either patients’ willingness to accept pain or functional capacity. Potential benefit of the study is that its results may aid to develop and corroborate clinical guidelines to tailor postoperative pain management in a way that will meet the unique needs of each patient.Our aims therefore were The Institutional Review Board of the Radboud University Medical Center  approved the study (2013/428). No informed consent was obtained from the participants because data were anonymized.This cross-sectional study was conducted on patients older than 18 years who had been admitted in a large regional academic medical center in the period from 1 January 2008 to 1 August 2013. The study used the prospectively collected pain assessments of postoperative patients who had been treated by the acute pain service (APS).We quantified the relationships between movement-evoked NRS and acceptability of pain, functional impact of pain, and a measure combining the two. The latter measure serves to judge whether or not a clinically desirable situation occurs where acceptable pain coexists with good physical functioning. A potential influence of gender, age or body mass index (BMI) was investigated.The APS nurses use a standardized multidimensional assessment to evaluate postoperative pain. This assessment includes: (1) the NRS for movement-evoked pain (NRS-MEP) , (2) theThe NRS-MEP is an 11-point numerical rating scale with end points representing the extremes of the pain experience: 0 = “no pain at all” and 10 = “worst possible pain”. All nurses and patients received education on how to use the NRS-MEP appropriately .The PO is determined by asking the patient whether the pain is acceptable or not, making it a binary yes-or-no variable .The NO scoring mirrors the Functional Activity Score (FAS) described by Scott and McDonald  and adopThe APS nurses rely on an operation-specific protocol offering clearly defined criteria to judge patient’s ability to perform physical activities on the first three days after surgery—like coughing, deep breathing, early movement and walking . Some exIn addition, combining PO and NO yields a third binary yes-or-no variable, i.e. PONO. This variable is not part of the multidimensional assessment at the bedside, but was created for study purposes only. One result for PONO is when “acceptable pain” accompanies “good movements”, thus reflecting a clinically desirable situation. The ultimate goal of postoperative pain treatment is that a patient qualifies the pain as acceptable and is able to perform appropriate movements. The other result for PONO is chosen for each of the three remaining combinations of PO and NO.The nurse-based, anesthesiologist supervised APS is part of the Department of Anesthesiology, Pain and Palliative Medicine. The organization of this type of APS has been described elsewhere , 22. Theinter alia values for NRS-MEP, PO and NO) into a new digital record of the APS database. As each visit yields one record in the database, multiple records per patient are possible per day. Data are entered on a mobile handheld computer wirelessly connected with the hospital system for real time registration.After each visit to a patient, the dedicated nurse enters the obtained data  into the logistic model , 23–25. Receiver Operating Characteristics (ROC) curves were made to estimate the ability of the computed models to correctly discriminate between those who found their pain acceptable or not, made appropriate movements or not, and those who combined acceptable pain with appropriate movements or not. First the sensitivity and specificity of NRS-MEP were calculated for each of the 11 points of the NRS-MEP score. Then the sensitivities (true positive fractions of subjects) were plotted versus 1-specificities  to obtain the ROC curves. The area under the curve (AUC) quantifies how well the NRS-MEP predicts PO, NO or PONO: the larger the area, the better. If AUC = 1.0, sensitivity and specificity equal both 100%. If AUC = 0.5, use of NRS-MEP is no better than flipping a coin.The statistically optimal cut-off point was determined where the sum of the sensitivity and the specificity minus one (Youden’s J-statistic) was maximal. Thus sensitivity and specificity were regarded as being equally important. This is the best cut-off point for the prediction of a positive response under the condition of equal “costs” of misclassifications.The Statistical Package for the Social Sciences , Statistical Analysis System , and R (R version 3.1.2 (2014-10-31); The R Foundation for Statistical Computing, Vienna, Austria) were used. Threshold of statistical significance was 0.05.15,394 assessments were obtained in 9,082 unique individual patients. For each of these patients data were obtained on: one of the three postoperative days, or any combination of two days, or all three days. Consequently, we had data from these 9,082 individual patients for 8,258, 4,522 and 2,614 of them on day 1, day 2 or day 3, respectively . The numBinary logistic regression analysis revealed strong mathematical relationships between components of pain assessments, but age, gender and BMI were of no influence. All fitted models were adequate .NRS-MEP was related to PO, NO or PONO on each of the three postoperative days . The procedure to assess the influence of age, gender and BMI on the prediction models yielded 27 P-values (three days times three covariates times three response variables). Of these 27 P-values, only one was below the threshold of statistical significance (P = 0.0423 for gender on the prediction of NO on day 1). As even in the absence of any relation between these covariates and the three outcomes, by pure chance one out of 20 P-values can be expected to be <0.05, these P-values were interpreted as indication that extension of the models with these covariates was not indicated. Therefore, we only present analyses using NRS-MEP as sole covariate. Details on the estimated models, including estimated regression coefficients, odds ratios and ROC curves, are given in The AUC for PO decreases across the days from 0.81 to 0.73. The latter figures indicate that NRS-MEP is not a perfect predictor for patients’ willingness to accept their pain. The areas under the curve for NO are larger than those for PO and PONO on each of the three days. The AUC for NO implies that the NRS-MEP is fairly accurate in predicting the NO for all three days .Four is the statistically optimal cut-off point for NRS-MEP based on the combination of patients’ opinion and the nurses’ observation. Nevertheless, 17%, 15% and 17% of those patients, who scored an NRS-MEP≤4, found their pain unacceptable or did not show good physical functioning or both, on day 1, 2, and 3, respectively. To our knowledge, this is the first study in a broad surgical population to quantify the relationships between movement-evoked NRS and acceptability of pain, functional impact of pain, and a measure combining the two as a clinically desirable situation. Since the outcome of pain assessments has clinical consequences for all surgical patients, we consider our findings important to all health professionals involved in peri-operative care.This study shows that the unidimensional NRS does not entirely reflect the multidimensional aspects of postoperative pain. Low pain scores do not guarantee that patients find their pain acceptable. Nor do high pain scores invariably mean that patients are not satisfied by their pain levels. Approximately one out of ten patients had unacceptable pain but reported a low NRS-MEP of 0–4. Despite a high pain score of NRS-MEP = 7, at least one in five patients were willing to accept their pain and, at the same time, performed the required physical activities .According to the Youden’s index, we found an ‘optimal’ NRS cut-off point for PONO of four. However, this threshold value is a rather poor predictor at the patient’s level. Approximately 16% of those patients who score an NRS-MEP equal to or lower than four, found their pain unacceptable or did not show good physical functioning or both. Taken together, the body of our findings points out that caregivers should prefer multidimensional assessment of pain, moving beyond the sole use of cut-off points on the NRS to make clinical decisions.Generally, low pain scores will not encourage health professionals to adjust pain treatment . When heTo fully estimate patients’ experience of pain an NRS score is not sufficient and other dimensions of pain should be assessed to balance treatment options , 34. TheAs nurses have more patient contacts than other health professionals, regular pain assessment and reassessments usually fall to the nursing domain . Pain asA specified value on the NRS has been frequently used as a single ‘cut-off point’ to divide patients into two categories: those who are in need of pain treatment and those who are not . HoweverThe ‚optimal’ cut-off point for NRS-MEP we defined here holds under the condition that costs of misclassifications are equal, thus weighing under- and over-treatment equally. However, our choice for this equality cannot be corroborated because it is unknown what is more harmful. In this study no outcome data were included and therefore we cannot discuss our results from this perspective. Nevertheless, we may point out two directions for future research. On one hand, questions should be answered whether treating unacceptable pain and better education of patients and professionals may prevent pain-related complications . On the In our study, we did not exclude patients because of incompleteness of the pain assessments. By doing so, we avoid the bias that would be induced by restricting the analyses to only patients without missing observations, the so-called complete case analysis. A complete case analysis is unbiased if data are missing completely randomly, meaning that the chance of data being missing is unrelated to any of the variables involved in the analysis. If data are not missing completely randomly, analyzing only the complete cases will probably lead to biased estimates . Even whThis study has limitations. First, there are no "gold standard" objective measures of the pain-related functional capacity in postsurgical patients . NeverthThe nature and strength of the relationships we found lead to clinically important findings and implications. Almost one in ten patients has unacceptable pain even if they report a low pain score. One in five patients with a high pain score accepts the postoperative pain and still moves appropriately. We encourage health professionals to use a multi-source pain evaluation by assessing NRS, the acceptability of the pain and physical functioning in order to balance pain treatment options and possible complications. The sole use of NRS cut-off points is not adequate. Adequate pain assessment appears to become a form of social transaction between patient and caregiver. Future research should focus on the improvement in pain-related outcomes in relation to multidimensional pain assessment and treatment decisions.S1 Table(PDF)Click here for additional data file.S2 Table(PDF)Click here for additional data file.S1 Fig(PDF)Click here for additional data file.


Complex relationships between depression and chronic pain have been reported in previous studies. However, only a few neuroimaging studies have investigated similarities and differences in neural systems underlying them. We examined the brain functions in the resting state of 43 patients with depression, 41 patients with chronic pain (somatoform pain disorder) and 41 healthy controls, by using regional homogeneity (ReHo) and functional connectivity analysis. Depressive symptoms were assessed by using the Beck Depression Inventory-Second Edition (BDI-II). ReHo values for the dorsolateral prefrontal cortex (DLPFC) significantly decreased for chronic pain patients, and functional connectivity between the DLPFC and thalamus decreased only for these patients. These findings are indicative of distinct brain functions related to depression and chronic pain. Understanding these differences would further elucidate the pathophysiology of these conditions. The association between depression and chronic pain has been supported by previous studies, including biological studies on neuroplastic, neurochemical, electrophysiological and hormonal variables, and psychological studies on pessimism and low self-esteem6. Furthermore, different randomized controlled trials have reported that antidepressants have beneficial effects on both depressive symptoms and pain perception8. Thus, it appears that depression and chronic pain might have certain commonalities.A number of epidemiological studies have shown that both depression and chronic pain lead to decreased productivity, social disability, increased suicide rates and higher health care cost11. However, other studies of depressive patients have indicated that they were less likely to perceive pain stimuli compared to controls13. To our knowledge, there is only one study that has directly compared pain perception between depressive and chronic pain patients. Normand et al. examined potential differences in experimentally induced pain perception and diffuse noxious inhibitory control efficacy (e.g. “pain inhibits pain” phenomenon) between depressive and chronic pain patients by using a tonic thermal test and a cold pressor test14. They reported that chronic pain could be distinguished from depression by pain ratings during the cold pressor test, which might be related to the pain inhibition system. Another study has suggested that efficacy of antidepressants against depressive symptoms and pain, including the dose and onset of efficacy, might be based on independent mechanisms15. Moreover, path analysis has suggested that analgesic effects of antidepressants in chronic pain patients might be separately caused by a direct analgesic effect and an antidepressant effect16. They have indicated that 80% and over of the change in pain intensity in chronic pain patients could be ascribed to a direct analgesic effect of antidepressants, with the remaining effect affected by an antidepressant effect.Subtle differences between chronic pain and depressive patients have been reported. For instance, certain experimental studies on pain perception using thermal, or electrical stimuli have shown that chronic pain patients exhibit higher pain sensitivity than healthy controls19. The amygdala, hippocampus, insula, anterior cingulate cortex (ACC) and the prefrontal cortex (PFC) show alterations in depression19. On the other hand, the somatosensory cortex, thalamus, amygdala, hippocampus, insula, ACC and the PFC are involved in chronic pain17. Various studies of the linkage between depression and chronic pain have reported the ACC to be a critical region21, and many neuroimaging studies have suggested that the ACC is significantly involved in depression or chronic pain23. On the other hand, based on the above-mentioned studies, distinctive brain regions involved in chronic pain would appear to be the somatosensory cortex and thalamus. Moreover, pain-related catastrophizing, that is mainly associated with etiology of chronic pain, and depression differed in the ways in which they impacted on pain experiences such as pain prediction24. Pain-related catastrophizing is closely related to activity in the dorsolateral prefrontal cortex (DLPFC)25, and of the PFC structures, the DLPFC seems to show the most differentiation between depression and chronic pain, playing different roles in each of these phenomena. Based on these points, we hypothesized that the activities of the DLPFC, thalamus and somatosensory cortex would be different between depression and chronic pain, and that the ACC would be a common, activated region in depressive and chronic pain patients, but not in healthy participants.Various brain regions involved in the processing of sensation, emotion, cognition, and nociception are associated with the neuropathology of both depression and chronic pain27. It is known that regional homogeneity (ReHo) has been shown to be sufficient to measure the local temporal synchronization of the time series of nearest neighbors during the resting state29, and the functional connectivity method can manifest longer inter-regional changes28. Previous ReHo or functional connectivity studies have suggested that these techniques were useful for increasing our understanding of neuropathology related to mental disorders or chronic pain32. Furthermore, coordinating the ReHo method in the seed-based functional connectivity analysis may facilitate the sensitivity of each analysis and reduce the uncertainty of seed extraction33, and more sensitive analyses could contribute to further elucidation of the complex neurocircuitry underlying depression and chronic pain.Recent evidence indicates that resting-state functional magnetic resonance imaging (R-fMRI) might be useful for investigating human cognitions, behaviors, emotions and somatic sensationsIn order to test the present hypotheses, we examined underlying resting state neural abnormalities of 43 depressive patients, 41 chronic pain patients, and 41 healthy controls using ReHo  and functional connectivity methods (long-distance connectivity). We conducted a one-way analysis of covariance (ANCOVA) with Beck Depression Inventory-Second Edition (BDI-II) scores as a continuous factor, BDI-II scores * group as the interaction and age and gender as covariates of no interest.p = 0.46 for age and p = 0.38 for gender). A one-way ANOVA revealed a significant main effect of BDI-II scores, F  = 113.8, p < 0.001, with BDI-II scores of depressive patients being significantly higher than those of chronic pain patients and the controls (Bonferroni p < 0.001). Moreover, BDI-II scores of chronic pain patients were significantly higher than those of the controls (Bonferroni p < 0.001).Detailed demographic and clinical characteristics of participants are presented in Table Regional brain functions of each group are shown in Fig. p < 0.05).To examine differences in resting-state regional brain functions among depressive, chronic pain and control groups, we performed an ANCOVA with group as a categorical factor, BDI-II scores as a continuous factor, BDI-II scores * group as the interaction term and age and gender as covariates of no interest, because it is important to assess the implication of depressive state for each group. Significant BDI-II score * group interactions were observed for the DLPFC  and in controls (post hoc test (Bonferroni) p < 0.01)  01) Fig. .z-score 4.32, cluster extent 68] . After controlled effect of BDI-II scores, functional connectivity values significantly decreased in chronic pain patients than in controls (post hoc test (Bonferroni) p < 0.01).A whole-brain ANCOVA suggested distinctive resting state regional brain functions for the right DLPFC in chronic pain patients, versus depressive patients or controls. We performed ReHo-seeded functional connectivity analysis to assess group differences. We conducted an ANCOVA with group as the categorical factor, BDI-II scores as a continuous factor, BDI-II scores * group as the interaction term, and age and gender as covariates of no interest. For the DLPFC seed, a significant interaction between BDI-II scores and group was observed in the thalamus [x = 15, y = −9, z = −3; This is the first neuroimaging study conducted with participants in the resting-state to have investigated differences in neural mechanisms between depressive and chronic pain patients. Results indicated that the DLPFC displayed lower ReHo values in chronic pain patients. Additionally, functional connectivity between DLPFC and thalamus was reduced in chronic pain patients.36. Our results corroborated these previous studies. It has been demonstrated that the DLPFC has greater control over pain perception, including its sensory and affective dimensions37. The present study showed a significant change in the DLPFC (BA46) of patients with depression. A number of previous studies conducted in the resting state showing abnormal DLPFC activity in depressive patients have indicated the involvement of the left DLPFC and the Brodmann area (BA 9)38. Abnormal DLPFC activation in this study was mainly indicated on the right side and BA 46, which might be suggestive of specific changes in patients with chronic pain.A significant decrease in ReHo values of the DLPFC, and a reduced functional connectivity between the DLPFC and thalamus was observed in the present study in patients with chronic pain, compared to patients with depression and healthy controls. A decreased functional or structural changes in the DLPFC of patients with chronic pain was also reported in previous studieset al. have proposed the important role played by the DLPFC (BA 9 and 46) in active manipulation of pain perceptions through the modulation of cortico-subcortical pathways37. The current study also demonstrated that the DLPFC was differently connected with the thalamus in the groups that were investigated. Many studies have demonstrated effective interactions between the DLPFC and midbrain, thalamic, striatal and cingulate structures of the limbic system40. Tran et al. have reported that thalamocortical mechanisms including the functional connectivity between the DLPFC and thalamus contributed to pain modulatory effects40. Previous studies on chronic pain have also suggested an abnormal connectivity between the PFC and thalamus43. The thalamus is also considered to play an important role in pain processing18. The present study speculates that poor functional connectivity between the thalamus and DLPFC, specific only to chronic pain patients, would be based on an abnormality of a top-down mode through the descending pathway from the PFC of inhibiting neuronal activities along the ascending pain pathway including the thalamus.Lorenz 45. It is possible that certain other localizations between depression and chronic pain influenced the present results.We have not found similarities in the ACC in depressive and chronic pain patients. Neuroimaging studies have shown that depression was mainly related to abnormal activations in Brodmann’s area 25 and that chronic pain was strongly linked to the dorsal ACC, such as the Brodmann’s area 24The present results were also dissimilar to our hypothesis that the somatosensory cortex would show more abnormal brain functions in patients with chronic pain. Many previous studies implicate the key brain limbic and cortical structures engaged in the pain-related cognitive, emotional and behavioral controls as the cause of chronic pain, which might have been associated with the result.The results of the present study are constrained by several limitations. Our exclusion criteria for participants did not include all possible treatment effects that might influence depressive states, and pain perceptions of patients, such as the use of antidepressants. We also could not rule out all treatment effects on brain functions that were observed in this study. Furthermore, many clinical characteristics such as pain perception and anxiety were not assessed. Finally, we excluded patients that have both depression and chronic pain. We believe that the strategy is useful to identify factors that are specific to chronic pain vs. depression, but it has also a limitation related to generalizability and clinical relevance.In conclusion, we investigated commonalities and differences in brain regions of depressive and chronic pain patients. The results suggest that the DLPFC and thalamus are associated with the dysfunction of pain-controlling networks specific to chronic pain. It is suggested that further comparisons be conducted to determine the similarities and differences in pathological conditions of depressive and chronic pain patients, which might contribute to the development of clinical treatment, among others.46, or in using the Mini-international neuropsychiatric interview for patients with MDD47. SPD is defined as the occurrence of one or more physical complaints for which appropriate medical evaluation reveals no explanatory physical pathology or pathophysiologic mechanism, or when such a pathology is present, the physical complaints or resulting impairment are grossly in excess of what would be expected from the physical findings46, and SPD is known to often occur in patients with chronic pain48. Details of psychiatric comorbidities and medication are shown in Table Participants were 43 patients with major depressive disorder , diagnosed according to DSM-IV-TR criteria, 41 patients with chronic pain , diagnosed according to DSM-IV-TR criteria as having SPD, and 41 control participants . All participants were Japanese people that provided written informed consent for participating in the present study. The study was designed and conducted according to a protocol approved by the ethics committee of Hiroshima University. The criterion for inclusion in the study was a diagnosis of MDD and SPD, as established by a psychiatrist with more than 10-years of experience in using the Structured Clinical Interview for DSM-IV (SCID) for patients with SPD49.BDI-II was used to assess depressive symptomsThe fMRI procedure was performed using a Magnex Eclipse 3 T Power Drive 250 . A time course series of 120 scans was acquired using T2*-weighted, gradient echo, echo planar imaging (EPI) sequences. Each volume consisted of 28 slices, with a slice thickness of 4 mm with no gaps, which covered the entire cerebral and cerebellar cortices. The time interval between two successive acquisitions of the same image (TR) was 3000 ms, the echo time (TE) was 46 ms, and the flip angle was 90°. The field of view (FOV) was 256 mm, and the matrix size was 64 × 64, giving voxel dimensions of 4 mm × 4 mm × 4 mm. Scan acquisition was synchronized to the onset of each trial. After functional scanning, structural scans were acquired using a T1-weighted gradient echo pulse sequence  to facilitate localization. After scanning, participants were asked whether they had kept their eye closed and whether they had remained awake during the scan. All participants confirmed that they had kept their eyes closed and remained awake.The first 10 images were discarded to ensure steady-state MRI signals during acclimation of participants and images collected after acclimation were further analyzed. Image preprocessing was conducted using Statistical Parametric Mapping (SPM8) software . First, slice timing and head movement corrections were conducted. Then, translation (mm) and rotation (degrees) values were obtained at each time point. All participants had less than 1.5 mm maximum displacement in the x, y, and z axes, and less than 1.5° angular motion during the scan. The images were then spatially normalized to the Montreal Neurological Institute (MNI) functional template (resampling voxel size = 3 mm × 3 mm × 3 mm).50, linear trends were removed and ReHo analysis was conducted using the R-fMRI data analysis toolkit , version 1.6. The ReHo analysis procedure was conducted according to the method described by Zang et al.29. ReHo was defined as the Kendall’s coefficient of concordance (KCC)51 of the time series for a given voxel with those of its nearest neighbors. Cubic clusters of 27 voxels were used for ReHo value of every cubic cluster to the central voxel. The square root was calculated at each frequency of the power spectrum. The sum of amplitudes across 0.01–0.08 Hz was divided by the amplitude across the entire frequency range. All ReHo maps were smoothed with a Gaussian filter of 9 mm full-width half-maximum kernel to manage the anatomical variability that was not compensated for by spatial normalization, and to improve the signal-to-noise ratio. Group-level analyses of the ReHo maps were conducted using SPM8. To separately detect regional brain functions in each group , a one-way analysis of covariance (ANCOVA) with group as the categorical factor, BDI-II scores as a continuous factor, BDI-II scores * group as the interaction and age and gender as covariates of no interest was conducted. In the whole brain analysis, cluster size thresholds were p (FWE corrected) < 0.05. Voxel parameter estimates of main effects were examined using post-hoc Bonferroni multiple comparisons performed by using SPSS version 16.0. The spatial coordinates provided by SPM8, which are in MNI brain space were converted to spatial coordinates of the Anatomical Automatic Labeling (AAL) atlas using the MarsBar SPM Toolbox (http://www.sourceforge.net/projects/marsbar).After preprocessing in SPM8 and a motion scrubbing procedurehttp://restfmri.net/forum/) version 1.6, to examine interactions between brain regions related to the experimental paradigm. To perform functional connectivity analysis, the first eigenvariate time series of brain regions identified as being activated by the previous analyses was extracted as a ROI. For each participant, the mean ROI time series were computed for reference time course. A whole brain analysis for the ROI was then conducted. Finally, Fisher’s z-transformation was applied to improve the normality of the correlation coefficients28. To detect between group differences, a one-way analysis of covariance (ANCOVA) with group as the categorical factor, BDI-II scores as a continuous factor, BDI-II scores * group as the interaction and age and gender as a covariate of no interest was conducted. Cluster size thresholds were p (FWE corrected) < 0.05.Furthermore, functional connectivity analysis of ReHo-based seeds was conducted using the R-fMRI data analysis toolkit (REST,


This study aims to compare the effectiveness of deep tissue massage (DTM) and therapeutic massage (TM) in the management of ankylosing spondylitis (AS) patients. This was a small, randomized clinical pilot study. Subjects were 27 men with diagnosed AS, randomly assigned to DTM group or TM group. Subjects in each group had 10 sessions of massage. Outcomes included the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), the Bath Ankylosing Spondylitis Functional Index (BASFI), Modified Schober Test, Finger to Floor Test, chest expansion, and pain intensity of lower back. There are no statistical significant differences between groups, except for BASDAI and pain intensity of lower back. This study suggests that massage may have clinical benefits for treating ankylosing spondylitis patients. Additional scientific research in this area is warranted. Ankylosing spondylitis (AS) is a chronic, progressive inflammatory rheumatic disease that predominantly affects the sacroiliac joints and spine and it may also involve the peripheral joints and specific organ like the eyes and bowels. AS leads to structural damage and functional impairments and a decrease in the quality of life . The majAS affects 0.1–0.5% of the population in Central Europe . The latThe treatment of AS patients requires pharmacotherapy together with nonpharmacological intervention, including physiotherapy modalities , 7. The The main goals of therapy are to reduce pain, prevent spinal deformation, and improve mobility and overall function . PhysiotThe Ottawa Panel believes that massage is an effective therapy in helping to relive subacute and chronic lower back pain (LBP) . FurtherHowever only a few studies, mostly case studies, have discussed the effect of massage therapy on LBP in AS patients , 18.The purpose of this study is to compare the effectiveness of deep tissue massage and therapeutic massage in the management of AS patients.The study was a randomized clinical pilot study with unblinded treatment and blinded outcome assessment. It included eligible patients who were recruited from the patients who were admitted to the rheumatology department at this time with a diagnosis of AS according to the modified New York criteria .After baseline assessments, 31 male patients were randomly assigned to Group DTM (deep tissue massage) and Group TM (therapeutic massage). Patients were randomized to DTM or TM using sealed opaque envelopes indicating treatment allocation. Randomization envelopes were prepared at study inception and random number sequence was obtained by flipping a coin. A research assistant not involved in the conduct of the study randomized patients, allocated treatment, and collected key data. Exclusion and inclusion criteria for this study are shown in All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments on comparable ethical standards. Informed consent was obtained from all individual participants included in the study.This study was approved by the Bioethics Committee of the University of Medical Sciences in Poznan . Patients from both groups, DTM (deep tissue massage) and TM (therapeutic massage), underwent a 30-minute session of deep tissue massage or therapeutic massage daily for 2 weeks . The massage was provided by 2 licensed therapists with at least 5 years of experience who were comfortable following the study protocol and had experience in the permitted techniques. Drugs prescribed earlier by their specialist were used in a consistent dosage.The massage therapist gave a series of 10 back massages intended to identify and alleviate musculoskeletal contributors to the participants' lower back pain. It was performed by using trigger point therapy and oblique pressure for a combination of lengthening strokes (extending a particular joint while at the same time working the muscle in the direction of the lengthening), cross-fiber strokes , anchor and stretch (anchoring at a tight area and stretching away from the spot), and freeing muscle from entrapment .The massage therapist gave a series of 10 back massages  intended to ease lower back pain and improve function by inducing a generalized sense of relaxation. Five distinct techniques were permitted: effleurage (gliding), petrissage , friction, holding, and vibration.The Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) consisted of 6 questions using a numerical rating scale (0–10) to measure the severity of fatigue, spinal and peripheral joint pain, localised tenderness, and morning stiffness  .The Bath Ankylosing Spondylitis Functional Index (BASFI) consists of 8 specific questions regarding function in AS and 2 questions reflecting the patient's ability to cope with everyday life. Each question was answered on a numerical rating scale (0–10). The mean score of the 10 items then provided the final BASFI score .Spinal mobility was assessed by the Modified Schober (MS) Test and Finger to Floor (FTF) Test. MS increase in the distance between two skin marks 10 cm above and 5 cm below the connecting line between “the Dimples of Venus” after maximal forward bending, measured with a tape. FTF is the distance between fingertips and floor measured with tape at maximal flexion of spine and pelvis while the knees are kept in extension .Chest expansion (CE) is defined as the difference in chest circumference at maximal inspiration and expiration at the level of the fourth intercostal space .Pain intensity was assessed by Visual Analog Scale (VAS). Participants were asked to place a line perpendicular to the VAS line at the point that represents their lower back pain during the past week anchored by “no pain” (score of 0) and “most severe pain”  .t-test or Mann–Whitney U test  was used for continuous variable to check difference between the DTM and the TM groups in baseline data. The normal distribution of each group was checked by the Shapiro-Wilk test. For each participant, change scores were calculated by subtracting the result of the final from those at baseline. In the study, mean change scores within groups and differences in change scores between groups were calculated, with 95% confidence intervals. Statistical analyses were performed using SPSS 24.0 for Windows. A p value of <0.05 was regarded as significant.For demographic data, independent The flow of the participants through the trial is shown in Patients from the Group DTM and the Group TM did not differ in basic characteristics before therapy in terms of age, BMI, ESR, CRP, BMI, BASDAI, BASFI, CE, MS, FTF, and PAIN .After intervention the DTM group showed a significantly greater reduction in BASDAI than the TM group . Effect After intervention the DTM group showed a significantly greater reduction in pain than the TM group . Effect This was a small, randomized clinical pilot study to compare deep tissue massage and therapeutic massage on lower back pain, disease activity, and the functional capacity of AS patients. A review of the available literature did not reveal any similar studies on AS patients. Regarding the role of physiotherapy in AS, research has mainly focused on exercise therapy and little has been documented on the other physical therapy modalities .Our results showed there are no statistical significant differences between groups, except for BASDAI and PAIN.The management of ankylosing spondylitis based on current evidence does not include massage therapy as an effective treatment for AS patient , 9, 11. Individual selection of therapy in ankylosing spondylitis is extremely important. Based on the rules for the implementation of deep massage, we can better interact with the patient. First of all, deep tissue massage is not a repeated sequence of successive movements. A therapist using the techniques of deep tissue massage should pay attention to how the tissue reacts to the treatment and continually analyses and reaches its loosening, so DTM is performed with force that is individually matched to the patient and depends on the depth which the tissue requires. Minor forces will be used when working on superficial fascia and greater force should be used on the back extensor. The angle between the massaged tissue and therapist's hand is also important, and it should not be greater than 45 degrees to achieve the best tissue relaxing effect . PossiblMassage therapist performing DTM of patient with AS must pay particular attention to the correct position of the patient, which should be comfortable and fully relaxed. Therefore, therapist may choose between supine and side position. DTM should be performed slowly and its goal is to achieve relaxation of soft tissue. Very important are palpation skills of the therapist, which will allow locating strained muscle fibers and trigger point and be let for specific work in these places. DTM will help reducing restrictive barriers or fibrous adhesion seen between layers of fascial tissue.In the literature we found 4 articles where massage therapy was used to treat an AS patient. Massage described as passive treatment was used in the research by Strumse et al. . It is dIn the literature we found two case studies using massage therapy in AS patients. Massage reduces back pain, stiffness, and fatigue and could be used as a complement for the standard care of people with AS . The redMassage decreased pain for acute, subacute, and chronic nonspecific LBP when compared with inactive and active controls mostly in the short-term follow-up period . Furlan There is a need for meta-analysis of larger and better studies with more specific populations, interventions, cointerventions, and outcome measures.This study is the first randomized clinical pilot study comparing the effectiveness of deep tissue massage and therapeutic massage on lower back pain in AS patients. An attempt was made to check the effects of deep tissue massage and therapeutic massage on the possible reduction of the intensity of lower back pain, decrease in disease activity, and improvement in functional capacity. Our study suggests that the use of deep tissue massage and therapeutic massage might have therapeutic results and that supplementing the comprehensive rehabilitation of an AS patient could be considered for use. The results obtained due to the small size of the groups do not allow for final conclusion about the role of massage in the treatment of AS but are very encouraging and can stimulate further studies in this field.