Background and Aims. No patient-reported outcome measures targeting pain have yet been validated for use in IBD patients. Consequently, the aim of this study was to test the psychometrical properties of the brief pain inventory (BPI) in an outpatient population with IBD. Methods. Participants were recruited from nine hospitals in the southeastern and western parts of Norway. Clinical and sociodemographic data were collected, and participants completed the BPI, as well as the Short-Form 36 (SF-36). Results. In total, 410 patients were included. The BPI displayed high correlations with the bodily pain dimension of the SF-36, as well as moderate correlations with disease activity indices. The BPI also displayed excellent internal consistency  and good to excellent test-retest values (intraclass correlation coefficient (ICC) 0.84–0.90 and Kappa values > .70). In UC, calculation of responsiveness revealed that only BPI interference in patients reporting improvement reached the threshold of 0.2. In CD, Cohen's d ranged from 0.26 to 0.68. Conclusions. The BPI may serve as an important supplement in patient-reported outcome measurement in IBD. There is need to confirm responsiveness in future studies. Moreover, responsiveness should ideally be investigated using changes in objective markers of inflammation. Inflammatory bowel diseases (IBDs), including ulcerative colitis (UC) and Crohn's disease (CD), are characterised by chronic, recurrent inflammation of the gastrointestinal (GI) tract , 2. In UIn IBD, abdominal pain is also reported to be common and in most cases attributed to inflammation. Growing evidence suggests, however, that the aetiology of pain in IBD may be multifactorial . It is wPain is a subjective experience, and, therefore, the measurement of these symptoms is dependent on self-reports by patients. Several methods and questionnaires have been developed to measure pain, including visual analogue scales and numeric- and verbal-rating scales . DevelopPain has been shown to have a causal influence on patient functioning . DespiteConsequently, the aim of this study was to test the psychometrical properties of the brief pain inventory (BPI) in an outpatient population with IBD.Participants were recruited from nine hospitals in the southeastern and western part of Norway as a part of a cross-sectional and longitudinal observational, multicentre study. Inclusion criteria were >17 years of age, a verified diagnosis of IBD  , and theSociodemographic variables were self-reported by patients, which included age, gender, smoking habits, and self-perceived IBD symptoms. Self-perceived IBD symptoms were obtained through patient classification of IBD symptoms during the last 14 days. Four possible scores were used: no symptoms, mild symptoms (do not interfere with everyday activities), moderate symptoms (do interfere with everyday activities and may result in sick leave), and severe symptoms .Disease activity was assessed through laboratory tests, faecal calprotectin  and the activity indices Simple Clinical Colitis Activity Index (SCCAI) and Simplified Crohn's Disease Activity Index (SCDAI) , 25. Phep < 0.001). The correlation between BPI interference index and the EORTC QLQ-C30 item on pain influence on daily living was 0.62 (p < 0.001) [The pain intensity section of the BPI consists of four items that are scored from 0 (no pain) to 10 (worst possible pain), whereas the functional interference section consists of seven items that are scored from 0 (no interference) to 10 (complete interference). A pain severity score is calculated from the mean of the four pain intensity items, and a pain interference score is calculated from the mean of the seven pain interference items [< 0.001) .The SF-36 is a well-validated, generic HRQoL questionnaire comprising 36 items , 26. Theχ2 test. Face validity was tested by distributing the questionnaire to 15 patients before field testing, to receive their input on item content, scoring, and structure. The Construct of the BPI was tested by using a principal axis factoring, Oblimin rotation with Kaiser normalisation, and eigenvalues >1. To find the optimal cut-point for mild, moderate, and severe pain, we deployed previously described methods, using the average pain item of the BPI [F-value (Wilks's lambda) was considered indicative of the scheme that was most useful for distinguishing mild, moderate, and severe pain.To assess the characteristics of the sample, we used descriptive analysis, frequencies, and the  the BPI , 28. AveConcurrent validity was tested through linear regression analysis, entering the well-established BP dimension of SF-36 as the dependent variable and average pain groups as the independent variable. We hypothesised that increased pain severity would be a negative predictor of BP. Construct validity was tested according to recommendations in the literature [ Convergent validity was calculated using binary correlation analysis (Spearman's rho) of the BPI, SF-36, and well-established disease activity indices. It was hypothesised that elevated pain (increased BPI scores) would correlate negatively with all SF-36 dimensions, but that the strongest negative correlation would be between the BPI and the bodily pain dimension. Increased disease activity indices were hypothesised to be positively associated with BPI scores. In UC, none of the items in the SCCAI specifically measure pain. However, we chose to correlate the BPI against the SCCAI items (a) general condition and (b) complications . In CD, the BPI was correlated with the SCDAI items (a) abdominal pain and (b) complications. Discriminant validity was calculated by comparing the correlation between the BPI items and their hypothesised dimension, with its correlation to other dimensions. Known-group validity was tested through one-way analysis of variance, by comparing mean BPI scores in patients reporting no, mild, moderate, or serious IBD symptoms. Moreover, we hypothesised that the SF-36 bodily pain would be negatively associated with increased pain level (BPI average pain). Post hoc Scheffe test was used to control for multiple comparisons. Floor and ceiling effects were investigated by calculating the percentage of patients scoring either the lowest or highest possible score in individual items, as well as in dimensional scores. If the number of lowest or highest possible scores on the BPI exceeded 15%, this was, according to recommendations [ Internal consistency reliability was tested with Cronbach's alpha. When answering the retest, patients were asked to indicate whether their condition was unchanged, deteriorated or improved since baseline. Test-retest reliability was measured using the intraclass correlation coefficient . Patients self-reported their perceived disease state at the second time of BPI assessment (4–6 weeks apart) using a question with three potential answers: “Compared to last time you completed the questionnaire, how do you evaluate your IBD condition today? (A) Unchanged (B) Improved, or (C) Deteriorated.” Based on this item, ICC values were calculated among those patients reporting to be in a stable condition. Responsiveness was calculated by comparing the BPI scores on baseline to those after 4–6 weeks in patients who reported either worsening or improvement in IBD symptoms. Both Guyatt's statistics and Cohen's d were used to calculate responsiveness. Guyatt's statistics was performed by dividing the mean change in individuals reporting either improvement or deterioration of symptoms with the standard deviation of the change score in those unchanged. Cohen's d effect size was calculated by comparing the mean difference between groups, divided by the pooled standard deviation. Operational definitions of 0.2, 0.5, and 0.8 were categorised as small, medium, and large, respectively. Missing data were treated as recommended in the literature; if data in half or less than half of the items within a scale were missing, they were replaced by the mean value of the respondent's completed items in the same scale [terature  using thndations , regardeme scale . All tesParticipation in the study was based on written informed consent and performed in accordance with the principles of the revised Helsinki Declaration. Approval was obtained from the Regional Ethics Committee (reference number: 2012/845/REK Sør-Øst A).p = 0.001) levels according to patient-perceived IBD symptoms was observed .In total, 452 patients were eligible and were invited to participate in the study. Further, 414 patients (91.6%) gave written informed consent, while 4 of these patients were excluded because the number of missing data exceeded 50%, leaving the number included for analyses at 410. Of these, 230 were diagnosed with CD and 180 with UC. Baseline characteristics of the included patients are presented in After inviting all 410 patients from baseline to complete the BPI a second time, 243 responded, corresponding to 59% of the original sample . None of those 242 patients at the retest had missing values on the BPI. In CD, 110 patients reported that their condition was unchanged compared with baseline, whereas 14 reported symptom improvements and 5 deterioration. The comparable numbers in UC were 86 unchanged, 20 improved, and 8 worsened.Overall BPI scores according to diagnosis are presented in F-value = 11.8). Using this classification, the distribution among patients was no pain , mild pain , moderate pain , and severe pain .Evaluating cut-off values for mild, moderate, and severe pain resulted in the optimal cut-off being (a) a score of 0 = no pain; (b) 1–3 = mild pain; (c) 4–6 = moderate pain; and (d) ≥7 = severe pain  included all four original BPI intensity items , whereas items with high loadings in factor two (0.58–0.93) included the seven original BPI interference items . face validity revealed no problematic issues regarding either item content or scoring. However, two patients called to attention the first and optional BPI screening item: “Throughout our lives, most of us have had pain from time to time . Have you had pain other than these everyday kinds of pain today?” This might potentially, if answered no, cause respondents to leave the rest of the items unanswered.Testing ofβ = −.63, p < 0.001, UC: β = −.65, p < 0.001). Construct validity tests revealed moderate to high negative correlation between the BPI intensity and interference dimensions and the bodily pain dimension of the SF-36. In addition, the BPI dimensions were positively correlated to the SCCAI and SCDAI ; no-serious (p < 0.01); mild-serious (p < 0.01); and moderate-serious (p < 0.01). In CD, significant effects were seen in no-moderate/serious (p < 0.01); mild-moderate (p < 0.01); and mild-serious (p < 0.05). Moreover, as presented in Figures Known-group validation showed a tendency of elevated BPI levels as the patients' subjective IBD symptoms increased . In UC, s p < 0.0; mild-seCronbach's alpha calculated, for UC and CD separately, revealed excellent alpha values regardless of diagnosis . Test-retest reliability of the BPI is presented in d effect sizes were generally lower in UC than in CD. In CD, all scores, except BPI interference in patients who reported a worsening, were moderate , which could have been useful in determining whether the observed change is meaningful to patients or not. MID is limited to the subgroup of people who are deemed to have had minimal change, but we did not include an adequate anchor to calculate these values.In conclusion, this study is the first to demonstrate that the BPI is an easily scored, valid, reliable measure of pain in IBD patients. Consequently, the BPI may serve as an important supplement in patient-reported outcome measurement in IBD. Although indications of responsiveness were found, there is still a need to confirm these in future studies. Moreover, responsiveness should ideally be investigated using changes in objective markers of inflammation, such as calprotectin.The Brief Pain Inventory is provided as supplementary material.


Background. We tested the hypothesis that warm-humidified carbon dioxide (CO2) insufflation would reduce postoperative pain and morphine requirement compared to cold-dry CO2 insufflation. Methods. A double-blinded, randomized, controlled trial was conducted to compare warm, humidified CO2 and cold-dry CO2. Patients with benign uterine diseases were randomized to either treatment (n = 48) or control (n = 49) group during laparoscopically assisted vaginal hysterectomy. Primary endpoints of the study were rest pain, movement pain, shoulder-tip pain, and cough pain at 2, 4, 6, 24, and 48 hours postoperatively, measured by visual analogue scale. Secondary outcomes were morphine consumption, rejected boli, temperature change, recovery room stay, and length of hospital stay. Results. There were no significant differences in all baseline characteristics. Shoulder-tip pain at 6 h postoperatively was significantly reduced in the intervention group. Pain at rest, movement pain, and cough pain did not differ. Total morphine consumption and rejected boli at 24 h postoperatively were significantly higher in the control group. Temperature change, recovery room stay, and length of hospital were similar. Conclusions. Warm, humidified insufflation gas significantly reduces postoperative shoulder-tip pain as well as morphine demand. This trial is registered with Clinical Trial Registration Number  DRKS00003853 ). This stands in contrast to the physiological conditions of the peritoneal cavity at body temperature of 37°C and continuous moistening of the peritoneum by the peritoneal fluid [2 has adverse effects on the peritoneal cells [During laparoscopic interventions, dry carbon dioxide . This procedure was chosen as it is frequently performed, conducted in a predefined order, and can therefore be standardized. Thus, unlike many other studies in the field of gynecology, in the present study potential impacts on the results caused by different surgical procedures are largely avoided. The primary aim of this study was to determine the impact of a laparoscopic gas conditioning system on postoperative pain development following LAVH.2 gas and cold, nonhumidified CO2 insufflation gas (standard gas) for several intra- and postoperative outcomes in LAVH.This was a single-center, double-blind, parallel-group, randomized controlled trial conducted in the Department of Gynecology, Obstetrics, and Gynecological Oncology, University Clinic for Gynecology, Pius-Hospital, Carl von Ossietzky University, Oldenburg, Germany, between April 2012 and January 2013. The trial was conducted to compare the use of warm, humidified insufflation COThe primary endpoint of the study was postoperative pain development at 2, 4, 6, 24, and 48 hours postoperatively for rest pain, movement pain, shoulder-tip pain, and cough pain as measured by visual analogue scale (VAS). Secondary endpoints were morphine consumption, rejected boli, temperature change during surgery, length of time spent in the recovery room, and duration of inpatient stay.Eligible patients were aged 18 years and over with benign uterine condition, at least one vaginal delivery, no previous surgeries in the case history that indicated extensive cicatrisation, no longitudinal laparotomy in the case history, no current oncological disease, no concurrent chronic disease requiring continuous intake of analgesics, ability to understand the study procedure, sonographic estimation of uterus weight below 400 grams, and preoperative estimation of surgery time between 1 and 2 hours. It was assumed that patients who have never given birth vaginally could experience more pain postoperatively due to a tighter vagina which is often associated with more manipulation during surgery to remove the uterus vaginally. Therefore, these patients were at first excluded due to possible effect confounding, but after 3 1/2 months of recruitment  it was recognized that these patients represent a substantive proportion of the patient population as many women had only birthed by cesarean section. To increase the recruitment rate and complete the study within a realistic time frame, it was decided to include patients who did not give vaginal birth. The generalizability of the results to the patient population in our hospital was thus extended.DRKS00003853).The study was approved by the Ethics Committee of the University of Göttingen, Germany, in April 2012 (committee reference number 16/2/12). The study was conducted according to the Good Clinical Practice guidelines provided by International Conference on Harmonisation (ICH). The study was conducted with the understanding and the consent of the patients. The trial was prospectively registered online with the German Clinical Trials Register (DRKS) which is an official recognized Primary Registry in the WHO Registry Network (unique DRKS study number μg) and maintenance of anesthesia with propofol titrated to effect. As the study was double-blinded, disclosure of treatment group was effected while patients were under anesthesia by a sealed, opaque, sequentially numbered envelope stating the treatment allocation. The study nurse responsible for pain measurement was excluded from any activities in the OR as well as from relevant staff and no further information was communicated to the study nurse. According to randomization, pneumoperitoneum was then either established and maintained with either cold (room temperature), dry (0% humidity) CO2 or with warm (35 ± 2°C), humidified (98% humidity) CO2. Humidification of CO2 was by the HumiGard MR 860 Surgical Humidification System  [2 insufflation, THERMOFLATOR from KARL STORZ was used  with pressure set to 14 mmHg and an upper gas flow limit of 6.5 L/min. All procedures were performed by several participating senior physicians. Study participants received LAVH with or without bilateral or unilateral salpingo-oophorectomy (SOO). The operation performed in the hospital can be broadly divided into three parts. The first part was a conventional laparoscopy in which the fallopian tube was dissected from the uterus (LAVH without SOO) or in which the infundibulopelvic ligament was dissected from the pelvic wall (LAVH with SOO) to prepare the uterus for vaginal removal. For abdominal entry during laparoscopy three incisions were made: one 10-millimeter incision in the umbilicus for the camera and two 5-millimeter incisions on the left and right lower abdomen for the instruments [The admission plan called for daily scrutinization of eligible patients and after an initial physical examination by a senior physician a decision was made as to whether the patient would be requested to participate in the study. All patients gave their informed consent one day before surgery and prior to any study activity. All patients received standard induced anesthesia with propofol, esmeron, and fentanyl 0.25 Zealand) , 5. For  Zealand truments . During 2 was recorded. Body temperature was recorded by intranasal probe at the beginning and the end of procedure by the anesthetic staff. Theater ambient (room) temperature was preoperatively adjusted to 18°C and recorded continuously by electronic thermometer from where the temperature at the mid-point of the operation was electronically obtained. All patients received an upper body thermal blanket both intra- and postoperatively . Applied intraoperative fluids were preheated to 38°C. After surgery, patients were transferred to the recovery room, and after evaluation of pain levels, postoperative nausea, and observation by nursing staff they were transferred to the ward. A study nurse, blinded to treatment allocation, recorded patients' pain levels by visual analogue score (VAS) at 2, 4, 6, 24, and 48 hours postoperatively in the following sequence: pain at rest, movement pain, shoulder-tip pain, and cough pain. As patients are usually not able to stand on the operating day, they were asked to rotate themselves, in bed, to the right and to the left side. At 24 and 48 hours postoperatively (first and second postoperative day), patients were asked about their pain at rest prior to arising in the morning, with all other pain levels recorded after ablutions. Shoulder-tip pain was defined as any pain that could be associated with gas insufflation, for example, pressing pain under the costal arch, chest pain during breathing or movement, and shoulder-tip pain in the proper sense. Pain was not regarded as gas related if the pain could be due to orthopedic problems. For measurement of cough pain, patients were asked to cough, strongly, twice. All pain scores were recorded by a single individual.Surgery duration was recorded by the OR staff (defined as time between first trocar insertion and last suture of the trocar incision), as well as the length of time the pneumoperitoneum was maintained for the first and second laparoscopic part (period between gas insufflation and gas exsufflation). Volume of insufflated COAll patients received pain medication according to a standardized protocol, as well as metamizole (1 gram i.v.) at the end of anesthesia. In the recovery room, patients received morphine titrated to analgesia or VAS score 3, respectively, followed by connection of the PCA  pump with the following settings: 1.5 mg morphine per bolus, bolus lock for 10 minutes, and a maximum of 30 mg morphine per 4 hours. Clonidine was not allowed due to its analgesic effect. Patients were allowed metamizole 1 gram i.v. on demand, or if they were allergic to metamizole; then 1-gram acetaminophen was administered. In the ward, patients received 1-gram metamizole i.v. in the evening on the operating day, and from the first postoperative day until the third postoperative day 1-gram metamizole  was administered four times a day at 6 a.m., noon, 6 p.m., and midnight. Additionally, patients were allowed their PCA pumps up to the second postoperative day for additional pain reduction when necessary. PCA pumps were software-monitored in order to obtain the applied boli data, which included boli dispensing requests which fell within the 10 min lockout period. Morphine consumption on the operating day referred to the time span between connection of the PCA pump and midnight; morphine consumption 24 hours postoperatively refers to the time span between 0:00 hours and 24:00 hours on the first postoperative day and morphine consumption at 48 hours refers to the time span between 0:00 hours and disconnection of the PCA pump on the second postoperative day. The time from connection of the PCA pump until midnight of the operation day was measured to ensure that the time patients had to use the pump on the operation day was equally distributed between groups. Intraoperative morphine and morphine applied in recovery room before connection of the PCA-pump were measured to ensure that patients in each group started with the same dose of morphine before they were able to self-medicate by PCA.p ≤ 0.05 and the probability of type-II errors (β) at 20%. This yielded a sample size of 44 subjects per treatment group at a power of 1-β = 80%. A repeated-measures ANOVA was fitted to within-subjects condition , with Greenhouse-Geiser's epsilon correction to degrees of freedom where deviations from sphericity were significant. Fisher's least significant difference (LSD) was used to evaluate significance in longitudinal data. Between-groups differences are presented as mean (95% CI) or median (95% CI) for parametric and nonparametric data, respectively, using the Mann-Whitney U test for nonparametric continuous variables with t-tests for continuous variables. The two treatment conditions were “Control” which received standard of care which was cold, dry CO2 for insufflation, and “Treatment” which received warm humidified CO2. Significance tests always report the two-sided value but also the upper one-sided value where it was significant, as the two-sided value gives the probability of different distributions for the two treatments, while the upper one-sided value tests if control (x) has more pain, analgesic consumption or rejected boli than treatment (y). Data were analyzed in Genstat V.16 , and statistical significance was accepted at the 0.05 level with no subgroup analyses planned or undertaken. There were also no interim analyses.Patients were randomly assigned to one of two parallel groups in 1 : 1 ratio to receive either warm, humidified or cold, nonhumidified gas. Randomization was effected with RITA (Randomization in Treatment Arms) software, version 1.27. Permuted-block randomization with block length of 4 and 6 was used. The sample size has been determined statistically by means of a power analysis. The primary endpoint was the investigation of postoperative pain by means of a VAS with values between 0 and 10. Normal distribution with the same standard deviation was assumed in both groups. The standard deviation used to calculate the power was obtained from previous studies and fixed at 2.5 , and difBased on the randomization list generated with RITA, an independent, external person prepared sequentially numbered, opaque, sealed envelopes. Envelopes were labelled with the respective randomization list number . The envelope contained the allocation to the respective treatment group printed on opaque paper in light letters, which served as additional privacy screen. After informed consent, patients received a study number identical to the number on the envelope. If a patient was a “drop-out” the corresponding envelope was discarded and the next patient received the next envelope. Envelopes were stored in a locked room and handed to OR staff by the study nurse shortly before surgery and after induction of anesthesia.The recording of pain, which was double-blinded with regard to the type of the treatment given, was carried out by a study nurse. All persons involved in the study were expressly advised that neither the patients nor the study nurse may obtain knowledge of the type of the treatment given. Patients were informed of the blinding via the patient information sheet and within the scope of the patient briefing.p < 0.001), and this is in contrast to the other types of pain where the pain decreased significantly over time (p < 0.001)  and that morphine use was statistically different between the groups suggests firstly that the self-administered morphine was effective at ameliorating the majority of the pain experienced by patients except for shoulder-tip pain and secondly that the self-administered morphine was an effect-confounder in the evaluation of the true difference in pain experienced between treatment groups. Of all the different kinds of pain analysed, shoulder-tip pain was the least responsive to morphine analgesic use, illustrating the severity of the pain. Morphine was therefore not as effective to control shoulder pain, as it was to control all other types of pain, such as rest pain. The fact that there is no difference in the pain between groups is evidence that the morphine controls the pain, but that the humidified group used less morphine to achieve the same pain control as the control group. It can therefore be assumed that the true pain felt by patients was reflected by the significant difference in morphine administered. However, it cannot be stated with absolute certainty whether the difference in morphine consumption is a surrogate parameter for the lower overall pain levels felt by the patients in the intervention group or the higher shoulder-tip pain experienced by patients in the control group. Statistically, it is unlikely that the effect occurred by chance, as shown by the relevant Several explanatory approaches for the development of shoulder-tip pain (STP) after laparoscopic surgery are current. It is assumed that the underlying process of STP is an irritation of phrenic nerve branches  caused bIn our study, no differences were observed regarding the temperature changes during surgery which is in line with findings in other studies . HoweverNo significant differences were found in the length of recovery room stay and length of hospital stay. These parameters were not adequately reflected by the study design as both parameters in our hospital were administrational issues only distantly related to the actual condition of the patients. We were not aware of the influence of this fact on the results prior to the study, and it is reasonable to assume that had the differences in pain levels and morphine consumption been used in an enhanced recovery and early discharge setting, then patients in the treatment group would have been discharged earlier, on average, than the control group. It is also reasonable to assume that this would lead to substantive cost savings to the institution in the medium-term, in terms of financial costs no longer incurred. The length of recovery room stay reflects the postoperative condition of the patients better than the length of hospital stay but it was too often influenced by the time the recovery room nurses needed to prepare the patients for the general ward depending on their capacity or personal situation, as well as the time the nurses in the ward had available to move patients from the recovery room. This was a secondary endpoint and it does not relate to the actual readiness of patients to be released from the recovery room as determined by an “Apgar” type scale. As an example, the 10-point surgical Apgar score proposed by Gawande et al. based on blood loss, heart rate, and mean arterial pressure could be applied in further studies as an aid to determine patients' readiness to move out of the recovery room . In our 2 gas on short-term intra- and postoperative outcomes are contradictory making it difficult for clinicians to decide whether a humidification system should be implemented in the surgical routine. A recently published large-scaled RCT investigating the impact of surgical humidifier during laparoscopic appendectomy in 190 children found no statistically significant clinical benefit on postoperative pain. Furthermore, the surgical humidifier had no effect on intraoperative core temperature and postoperative recovery parameters [The results of studies conducted to investigate the influence of warm, humidified COrameters . Additiorameters . Anotherrameters . This strameters . The metrameters –35. Our 2.As far as we know, 6 studies have so far been conducted in the field of gynaecology , 36–39. A limitation of the present study was firstly that only females were operated on and only one operation was investigated. Though the generalizability may be limited by that fact that the restrictive study design may contribute to the reason why, unlike in other studies, a difference between groups was found. However, since the main reason for shoulder-tip pain is the laparoscopy itself and not the type of surgery (except for surgery affecting the diaphragm) it is likely that the results can be generalized to other laparoscopic procedures as well. Secondly, only short-term laparoscopy was investigated and we cannot state with certainty if the effect is also present after longer laparoscopic procedures, but it is likely that there is no difference or that the effect is even greater as more damage to the peritoneal cells may occur when the pneumoperitoneum is maintained over a longer period of time. Thirdly, all patients had a vaginal tamponade until the morning of the first postoperative day and all patients had a drainage which was removed during the first postoperative day. Both may have influenced pain sensation. Since all patients received a tamponade and drainage it would not have caused a difference in pain sensation between groups. Furthermore, every patient was encouraged during every questioning to discriminate between intrapelvic pain and pain due to the vaginal tamponade and the patients confirmed that they were able to distinguish between intravaginal pressure of the tamponade and the actual intra-abdominal pain location. Finally, the number of patients investigated was not large, but according to the preceding power analysis it was adequate to answer the research question.The results of the study are important for clinicians as they show that with humidification of the insufflation gas, shoulder-tip pain can be significantly reduced which in turn could lead to faster recovery and earlier discharge of the patients. The cost savings through reduction of morphine usage are negligible as morphine is not expensive and this cannot be weighed against the higher additional costs of the humidification system. Nevertheless, the possible faster recovery of patients may be an important factor to consider when thinking about costs as many hospitals already strive to discharge their patients as soon as they feel ready to leave. The cost savings, in terms of costs no longer incurred, are likely to be substantive and pivotal in the short-term future as patient medical costs and reimbursement are increasingly scrutinized. Further studies therefore could also investigate the cost effectiveness of the humidification. Additionally, it could be investigated if the observed effect is even greater after longer laparoscopies but it is advisable to concentrate on well standardized procedures.


In patients with idiopathic intracranial hypertension (IIH) headache often persist as a disabling symptom even after intracranial pressure (ICP) has normalized. Yet very little is known about the mechanisms of chronification.To explore pain perception in patients with IIH in a controlled design at time of diagnosis and after 3 months of treatment.We explored pain perception in patients with newly diagnosed IIH by Quantitative Sensory Testing (QST) measuring cephalic and extra-cephalic supra-threshold pain ratings and pain thresholds for pressure and electrical stimulation. QST was performed at diagnosis and after one and three months. ICP was measured at baseline and at the 3-month follow-up. QST measurements from sex-matched controls were used for comparisons. Headache was assessed by monthly standardized interviews and headache diaries.At baseline IIH patients (n=28) showed no consistent abnormalities in pain sensitivity or thresholds . Although headache improved markedly and ICP normalized in 52%, there was no consistent change in pain sensitivity from baseline to follow-up . Patients with (54%) and without persistent chronic headache (46%) 3 months after diagnosis showed no different pain perception either at baseline or at the 3-month follow-up.Although headache persisted as a chronic symptom in half of the patients we found no evidence of increased central pain sensitivity suggesting that headache chronification in IIH is caused by mechanisms other than central sensitization.


P > 0.05), cervical spine ROM, and a reduction of spinal pain. The conclusion is that there is a significant association between TMD treatment and reduction of cervical spine pain, as far as improvement of cervical spine mobility.Temporomandibular dysfunction (TMD) is considered to be associated with imbalance of the whole body. This study aimed to evaluate the influence of TMD therapy on cervical spine range of movement (ROM) and reduction of spinal pain. The study group consisted of 60 patients with TMD, cervical spine pain, and limited cervical spine range of movements. Subjects were interviewed by a questionnaire about symptoms of TMD and neck pain and had also masticatory motor system physically examined (according to RDC-TMD) and analysed by JMA ultrasound device. The cervical spine motion was analysed using an MCS device. Subjects were randomly admitted to two groups, treated and control. Patients from the treated group were treated with an occlusal splint. Patients from control group were ordered to self-control parafunctional habits. Subsequent examinations were planned in both groups 3 weeks and 3 months after treatment was introduced. The results of tests performed 3 months after the beginning of occlusal splint therapy showed a significant improvement in TMJ function ( Recent years have seen a significant increase in the number of patients suffering from temporomandibular disorders (TMD) . AccordiThe issue of relationships between temporomandibular disorders and body posture is still a source of speculations. The knowledge about connections between distant body districts has to be proven by appropriate diagnostic procedures and instruments.TMD are musculoskeletal disorders needing a multidisciplinary effort to manage with other professionals  .Because of the variety of TMD symptoms, many patients had a history of multiple treatments and medications and were treated previously by laryngologists, neurologists, or physiotherapist, but the therapy did not bring the expected, long lasting results. According to currently prevailing theories, temporomandibular dysfunction is considered to be associated with imbalance of the whole body .In addition, the body as a whole operates on the principle of compensation, when it comes to disturbances in the upper quarter, such as increased muscle tension; this will lead to compensatory changes within the muscle tension in the spinal region so as to force the correct position/posture. These adaptive changes occur at all levels, within tolerance of the body , 6.When the body capacity to compensate for the pathological changes progressing in given areas is exceeded, however, imbalance sets in and pathological symptoms will appear. Each individual, obviously, has a unique compensation limit beyond which such symptoms are triggered off.It was pointed out by many authors that pain in the upper quarter and masticatory motor system may be caused by cervical spine disorders  and vice versa –9.It could be explained by specific functional and morphological connections between the cervical and temporomandibular regions.The sample was comprised of 60 individual  and was divided into two groups with randomization. Study and control groups both consisted of 30 people with TMD, cervical spine pain, and limited cervical spine range of movements (ROM). Subjects were directed from Cooperating Orthopaedic Service.Groups were not different regarding age and gender.Patients from both groups met the criteria for inclusion and exclusion of studies .Patients from both groups were recruited from cooperating clinics and previously diagnosed by an orthopaedist who excluded morphological and degenerative changes of cervical spine. Cervical spine pain was diagnosed by an orthopaedist according to the Neck Pain Task Force recommendations .Each patient had to have had cervical spine pain for at least 12 months in multiple episodes at a frequency of at least once a week. Patients were included in the study if having pain in the area between occiput and C7.Subjects gave written consent to participate in the study. The study was approved by the Ethics Committee of the Medical University of Silesia (number KNW/0022/KB1/6/I/10 from 16.03.2010).Each patient was examined three times. At the 3-week and 3-month evaluations, symptoms of TMD and cervical spine pain and mobility were studied.medical history and physical examination, based on a survey card (according to RDC/TMD);analysis of pain, using the visual analogue scale (VAS) and the cervical Oswestry scale for the cervical spine;TMJ functional evaluation by JMA device;cervical spine motion evaluation with the MCS device.In order to describe individual TMD symptoms, the entire sample filled out a questionnaire according to research diagnostic criteria for TMD, the translated Polish version (RDC/TMD axis I). The questionnaire focuses on symptoms specifically in the jaw-face, neck, shoulder girdle, intensity of spinal pain, and any other complaints of TMD and spinal origin. Presence of symptoms was marked according to duration, frequency, and intensity. The survey card was completed by each patient 3 times during three consecutive examinations which enabled a comparison of symptoms between groups according to treatment provided in treated group.The examination included the following:On a questionnaire, patients indicated the intensity of spinal pain experienced at the time of examination on a 100 mm visual analogue scale (VAS). Additionally, subjects described symptoms of pain and reduced mobility of cervical spine by filling in the cervical Oswestry scale.Clinical examination was performed according to RDC/TMD guidelines, too.Previously trained examiner assessed face symmetry, dentition, and occlusion, as far as “upper quarter” muscle tenderness to palpation with an emphasis on the masticatory muscles, trapezius muscles, suprahyoid muscles, infrahyoid muscles, sternocleidomastoid muscles, and neck muscles in the region of the linea nuchae. Each time the muscle tension was examined by the same examiner.Mandibular motion was recorded using jaw motion analyzer (JMA) from Zebris, (GmBbH) and the software provided (WinJaw) . The devThe subjects were provided with an explanation as to the objective of the axiographic examination and its course as well as what types of mandibular movements should be made and how. For each examination, it was necessary to make a paraocclusal clutch mounted on the vestibular surface of the lower teeth and fitted with an electronic sensor. The tool was made of light-cured Multitray (Espe).The study was based on the performance of patients' movements: opening and closing of the mandible, lateral movements, protrusion, and retrusion. To avoid bias, all subjects performed each trials three times. For each movement, the baseline position was the mandibular rest position. It seems that the rest position should be the starting point when assessing the motor function of the stomatognathic system using instrumental techniques .The advantages of this system are the ease of use and a positional accuracy of about 100 micrometers. Software allowed creating data report, which consists of graphic diagrams of TMJ function .Afterwards, the MCS  ultrasonic-based device was used to collect external kinematic data of the cervical spine movements. Patients with a neutral (comfortably seated) position performed maximal head movements: flexion, extension, rotation to the right and left side, and lateral flexion movements. Each movement was repeated three times in order to minimise measurement errors. The system was calibrated before each measurement. Data were monitored in a real time .Thanks to the repeatable measurements, values were found describing the cervical spine ROMs, presented in the form of relevant graphs.After the subjects' examination, data containing information about the quality and range of movement in both the TMJ and cervical spine were stored on a personal computer.After the first examination, each patient selected for the treated  group was supplied with an occlusal splint. Every patient suffered from TMD of muscular origin (RDC/TMD axis I); therefore, subjects were supplied with an occlusal splint SVED . SVED is a removable, flat-plane appliance which makes contact only with the anterior teeth in the opposing arch . It diseThe SVED appliance is used in case of hyperactivity of masticatory muscles, without the occlusal reason of TMD . It is uAccording to many researchers, there is no ideal way to handle the problem of control treatment, especially in splint studies. The use of a placebo control group can balance the nonspecific effects in the treatment group and allow for independent assessment of the real treatment effect . In our P < 0.05 was assumed to be significant while the test probability of P < 0.0001 was highly significant.The statistical analysis of the results was performed using the statistical package STATISTICA 9.0 (StatSoft). The test probability of 60 subjects were examined: 30 belonged to the treated group and 30 to the control group. Patients were randomly admitted to groups. The characteristics of age and gender for both groups are shown in All patients were simultaneously assessed by the same examiner.Referring to TMD research diagnostic criteria, in patients from both treated and control groups myofascial pain (I) or disc displacement with reduction  was diagnosed.After a three-month therapy with an occlusal splint considerable improvements of TMJ function were found in the experimental group, with 78% of the subjects reporting no DDR symptoms or acoustic phenomena like clicks during mandible movements; the abduction path of the mandible was symmetrical, and there was no pain during the movements .Most interestingly, however, there were changes on the condyle path in the TMJ during the measurements made with a JMA. Deviations within the condylar path which had been noticeable in the first examination (such as lack of symmetry between the length of the path in the right and left TMJ) became reduced in 28 subjects as a result of the treatment, and during the third measurement, the graphs of the condylar paths were asymmetrical on both sides in as few as four subjects. In 24 subjects, there were considerable improvements, which also improved the TMJ function.In the control group, no changes in the TMJ function were observed in the clinical examination or instrumental check with a JMA in successive examinations.Muscle tension was examined by palpation by the same examiner. In all subjects, upper quarter muscle tenderness  was diagnosed during three consecutive examinations. The presence of muscle pain and tenderness during palpation was registered in both experimental and control groups.During the third examination, the muscle tension of the subjects in the experimental group lowered considerably and they reported lack of pain in the examination by palpation. Out of the 27 subjects in whom intensified tension of the examined muscles had been found, 22 reported no complaints during the third examination. No significant changes were found in the control group.The whole group showed cervical spine pain. Cervical spine pain according to VAS scale in a treated group significantly improved during three-month therapy .During treatment, cervical spine pain diminished and after 3 weeks it occurred in 39% of subjects and after 3 months pain was only in 8% subjects from treated group (2 subjects).P < 0.0001).The difference between treated and control groups was statistically significant ; that is, there were more subjects in the experimental group with the result conforming to the norm.For the anteflexion movement, the improvement of the results was highly significant (P = 0.0082); that is, there were more subjects in the experimental group with the result conforming to the norm.Likewise, for the retroflexion movement, the results were improved by a highly significant factor (P > 0.05) changes were found; that is, there was no ROM improvement in the cervical spine towards the values in the norm.In the control group, no significant (The results of improving the mobility and reduction of cervical spine pain influenced the cervical Oswestry scale score. The average score on the first examination in a treated group was 9.22 points and during therapy, after 3 months, the average score changed to 3.71.The results obtained have confirmed a correlation between the pathologies and the positive impact of treatment within the motor aspect of the stomatognathic system on the alleviation of spine pain, even in subjects experiencing such pain for many years.It is important to understand the complex interrelations between the stomatognathic system and pain and dysfunctions in other areas of the body in order to be able to treat patients more efficiently and effectively at the initial stage, when painful symptoms appear and when curing them is possible as well as much swifter and more efficient. To be able to make successful therapeutic interventions, dental surgeons should cooperate in an interdisciplinary fashion with neurologists, orthopaedists, or laryngologists. They all should also take such interdependencies into account in their diagnostic work with their own patients.Scientists often note the importance of a holistic approach to therapy. There are many voices in favor of this approach that symptoms of the disorder are usually not isolated and the dysfunction of one region of the body also applies to other regions –20.Although the etiology of cervical spine pain very often remains unexplained, medical specialists in many cases report the comorbidity of dysfunctions in the stomatognathic system and the pain syndrome in the cervical spine . NumerouIn case of TMD, there are often large discrepancies between therapists concerning type of occlusal splint most appropriate to use. Many types of splints can be distinguished, for example, stabilization splint, repositioning splint, relaxation splint, or splints only for protecting oral tissues. SVED splint, which is a typical relaxing appliance, was used because of its influence on jaw muscles. No studies about different types of splints used in patients with both TMD and spinal pain were found .Our studies as well as the clinical followup suggest that TMD is very frequently present along with pain in the cervical spine. The key aspect of the studies described here is the considerable ROM improvement in the cervical spine and the elimination of cervical spine pain felt there by the subjects in the experimental group. Taking into account the results of our study, it seems obvious that interdisciplinary cooperation between orthopedist, laryngologist, neurologist, and dentist is necessary and essential.


Autologous conditioned serum (ACS) is an autologous blood product that has shown efficacy against knee osteoarthritis (OA) in randomized controlled trials. However, there are few reports of its effectiveness in everyday practice. Here, we report clinical efficacy results from a two-year prospective observational study of patients with highly symptomatic knee OA who received ACS in conjunction with physiotherapy.118 patients with unilateral knee OA (Kellgren-Lawrence grades I–IV), who were candidates for surgery but instead chose conservative treatment, were treated with a combination of four intra-articular injections of ACS (2 mL each) once weekly over four weeks and subsequent physiotherapy applied 4 weeks after ACS injection. Main endpoints of the study were pain  assessed at 0, 3, 6, 12 and 24 months, and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) global score, assessed at 0 and 24 months. The effect size (Cohen’s d) was calculated for pain and WOMAC outcomes, with effect sizes >0.8 considered large.By 3 months, there were significant improvements in pain (NRS) from baseline , which were maintained over 24 months. Mean WOMAC global score was reduced at 24 months compared to baseline , as were WOMAC subscores of pain  and function . Effect sizes for pain (>5) and WOMAC improvement (8.0–13.6) were very large. Only one patient received total knee joint replacement during the study. Clinical improvement did not correlate with gender, age, Kellgren-Lawrence grade, or body mass index.Treatment with ACS and physiotherapy produced a rapid decline in pain, which was sustained for the entire two years of the study. This was accompanied by a large improvement in WOMAC scores at two years. These results confirm that ACS combined with physiotherapy is an effective treatment for OA of the knee. Osteoarthritis (OA) is a common, incurable and difficult to treat disease. Joint surgery is an option in progressed cases ; howeverAutologous conditioned serum (ACS) is an alternative intra-articular therapy for the treatment of OA. ACS is derived from autologous blood by incubating venous blood for six hours in a specially designed syringe containing glass beads. Exposure of blood to the beads induces peripheral blood leukocytes to produce increased amounts of anti-inflammatory cytokines such as IL-1Ra . The posThere have, however, been few reports of the experience of physicians using ACS in orthopedic practice outside the rigorous confines of an RCT. Here, we present results from an independent, investigator-initiated, prospective, observational study of ACS treatment in combination with physiotherapy in knee OA outpatients. As these patients had highly symptomatic disease, they were candidates for surgical intervention, but instead elected to undergo conservative treatment. The objective of this study was to evaluate the clinical symptoms in these patients following two years of ACS treatment combined with subsequent physiotherapy compared to baseline.This two-year, single-site, prospective observational study was conducted from 2009 to 2011 and included patients ≥18 years of age with OA Kellgren-Lawrence grade I–IV and painful OA of the knee . X-ray based grading for knee OA was performed by two independent observers according to the Kellgren-Lawrence criteria. Patients were only included in the study if they preferred conservative treatment to possible surgery and agreed to a follow-up period of 2 years. Exclusion criteria included pregnancy, neurological disorders, joint infection, spondyloarthropathies, gout, hyperlipidemia, rheumatoid arthritis, sarcoidosis or pathologies of the lower limb which would interfere with the evaluation of knee OA. Patients were also excluded if they had received intra-articular injection(s) or Symptomatic Slow-Acting Drugs in OsteoArthritis (SYSADOA) in the past two months, oral corticoid treatment in the last month, or oral NSAID treatment or topical corticoid treatment in the past week. All patients agreed to anonymous data analysis and publication by signing an informed consent form before treatment. This study was approved by the Ethics Committee of Clinical Investigation, Hospital Ruber Internacional, Madrid, Spain, and was conducted in conformance with this decision.®II syringes  and incubated at 37°C for 6 hours. Subsequently, the blood was centrifuged at 3000 g for 10 minutes. The supernatant conditioned serum was collected, filtered through a 0.22 μM syringe tip filter  and either injected intra-articularly or frozen at -20°C until clinical use. Patients received four intra-articular injections of 2 mL ACS once weekly over four weeks.For ACS therapy, 4 x 10 mL of blood was collected from each patient using four EOTPatients received a uniform rehabilitation program starting four weeks after the last injection of ACS which consisted of three 50 minute rehabilitation sessions per week for 10 weeks, 30 sessions in all. Physiotherapy consisted of a combination of physiotherapy and transcutaneous electric nerve stimulation (TENS). Rehabilitation included kinesiotherapy, muscular strengthening, joint range of motion exercises and TENS.Clinical outcome data were collected during the 24 month observation period. Clinical examinations and pain  were recorded at 0, 3, 6, 12 and 24 months, with “0” indicating no pain and “10” indicating worst pain. The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score was recorded at 0 and 24 months. WOMAC is a patient-administered, quality-of-life instrument validated for the assessment of patients with OA . The WOMData were tabulated using MS Excel, which was also used to produce basic statistics and graphs. T-tests (2-sided) and effect sizes were computed using programs written in Visual Basic for Applications by S. Cleveland (University of Düsseldorf). A p-value <0.05 was considered significant. The effect size (Cohen’s d) is a dimensionless measure of change due to treatment and is independent of sample size. It is computed as the difference between groups and pre- and post-records, divided by the combined standard deviation of these data sets. Effect sizes >0.8 were considered large.In total, 118 routine outpatients  were enrolled in the study. The mean age at baseline was 59.1 (range 34–81); full baseline demographics are given in Mean pain (NRS) improvements after 3, 6, 12 and 24 months were statistically significant with decreases of -63%, -66%, -65% and -63%, respectively, compared to baseline (p<0.001). Improvements in pain scores observed at 3 months were maintained in the follow-ups up to 24 months , Fig 1. Clinical effect as measured by pain outcome did not appear to correlate with gender, age, Kellgren-Lawrence OA grade, or BMI . A trendOnly one patient was lost to follow-up. This individual entered with a Kellgren-Lawrence score of IV and a pain (NRS) score of 8 which improved to 4 at 6 months and was recorded as 5 at 12 months. Despite reporting improvements in pain, this patient elected to receive a total knee endoprosthesis after 1 year of treatment. Data for this patient at 12 months were applied to the 24 month time-point using last observation carried forward (LOCF) imputation. All other patients completed the 24-month study without requiring surgery. ACS was well tolerated, with no new safety signals detected in this study.ACS has shown promise in RCTs as a local therapy for OA of the knee , 6, but et al. who reported excellent improvement in pain in OA of the hip with little correlation to radiologic staging of the disease [It is interesting to speculate that the large degree of improvement seen here reflects the highly symptomatic nature of the patients’ OA when entering the study. It is also noteworthy that strong symptomatic improvement extended across all grades of OA, including those with the most severe disease. This observation agrees with findings by Baltzer  disease . Age, geThis study did not address whether the combination of ACS and physiotherapy influenced joint degeneration, and therefore might be disease-modifying. It also made no attempt to determine the precise mode of action of ACS, which is still under investigation. In joints affected by OA, chondrocytes and synovial cells produce increased levels of pro-inflammatory cytokines such as IL-1, which contribute to the destruction of articular cartilage . The balet al., patients with knee OA were randomised to ACS, HA, or intra-articular placebo. In this study, ACS was shown to be significantly superior compared to HA and placebo for all efficacy outcome measures and time points [et al., improvements in WOMAC and VAS scores were also observed with ACS treatment, but these were smaller (approximately 20% for pain and 19% for WOMAC at 12 months compared to baseline) and were not significantly different to placebo [et al., however, which limit the conclusions that can be drawn from these results. These include the unknown analgesic dose use during the study and low disease severity at enrolment.The improvements in pain and WOMAC score reported in this study are supported by data from RCTs of ACS in knee OA , 6. In te points . Followie points , in lineDirect comparison of ACS with other treatments for OA is challenging due to differences in study design, conflicting clinical trial results and the lack of head-to-head studies. Although total knee arthroscopy is often considered the final treatment option for patients with knee OA, a number of studies have suggested that arthroscopic surgery does not provide any additional benefit for patients with OA –19. The A major limitation of this study is the lack of control group, as this study was planned and performed as a prospective observational study. This makes it difficult to assess whether these patients’ symptoms improved due to the addition of ACS to physiotherapy, or whether their symptoms improved due to physiotherapy alone. However, in our experience, physiotherapy alone produces a pain improvement of about 25% (data not shown). In addition, up to 35% primary improvement has been described for intra-articular placebo injections in trials of OA ; placeboCombination therapy of ACS followed by physiotherapy significantly reduced OA symptoms compared to baseline in a real life outpatient cohort with severe osteoarthritic knee pain, independently of disease stage. The authors consider the combination of ACS and physiotherapy as a modality that can improve quality of life in OA patients and may postpone joint surgery.S1 Fig(PDF)Click here for additional data file.S1 Table(DOCX)Click here for additional data file.


Using a semi-structured caregiver questionnaire and MRI voxel-based morphometry in patients with frontotemporal degeneration or Alzheimer’s disease, Fletcher   n = 58, 25 female, aged 52–84 years, representing the major clinical syndromes and representative pathogenic mutations in the C9orf72 and MAPT genes) and a comparison cohort of patients with amnestic Alzheimer’s disease . Neuroanatomical associations were assessed using blinded visual rating and voxel-based morphometry of patients’ brain magnetic resonance images. Certain syndromic signatures were identified: pain and temperature symptoms were particularly prevalent in behavioural variant frontotemporal dementia (71% of cases) and semantic dementia (65% of cases) and in association with C9orf72 mutations (6/6 cases), but also developed in Alzheimer’s disease (45% of cases) and progressive non-fluent aphasia (25% of cases). While altered temperature responsiveness was more common than altered pain responsiveness across syndromes, blunted responsiveness to pain and temperature was particularly associated with behavioural variant frontotemporal dementia (40% of symptomatic cases) and heightened responsiveness with semantic dementia (73% of symptomatic cases) and Alzheimer’s disease (78% of symptomatic cases). In the voxel-based morphometry analysis of the frontotemporal lobar degeneration cohort, pain and temperature symptoms were associated with grey matter loss in a right-lateralized network including insula  and anterior temporal cortex (P < 0.001 uncorrected over whole brain) previously implicated in processing homeostatic signals. Pain and temperature symptoms accompanying C9orf72 mutations were specifically associated with posterior thalamic atrophy . Together the findings suggest candidate cognitive and neuroanatomical bases for these salient but under-appreciated phenotypic features of the dementias, with wider implications for the homeostatic pathophysiology and clinical management of neurodegenerative diseases.Symptoms suggesting altered processing of pain and temperature have been described in dementia diseases and may contribute importantly to clinical phenotypes, particularly in the frontotemporal lobar degeneration spectrum, but the basis for these symptoms has not been characterized in detail. Here we analysed pain and temperature symptoms using a semi-structured caregiver questionnaire recording altered behavioural responsiveness to pain or temperature for a cohort of patients with frontotemporal lobar degeneration ( C9orf72 mutations  are a diverse group of proteinopathies characterized by selective degeneration of distributed brain networks involving the frontal and temporal lobes. Altered processing of sensory signals is an important feature of these diseases . PatientC9orf72 mutations  of patients’ brain magnetic resonance images. We hypothesized that pain and temperature symptoms would be over-represented in behavioural variant FTD and semantic dementia versus progressive non-fluent aphasia (PNFA) and Alzheimer’s disease, and more specifically, in patients with yndromes ; and parn = 21; semantic dementia, n = 17; PNFA, n = 20) or for Alzheimer’s disease led by decline in episodic memory . All patients had MRI profiles of regional brain atrophy concordant with their clinical diagnosis; no patient had radiological evidence of significant or strategic vascular damage. Genetic screening revealed 11 patients with a pathogenic mutation . All patients with a genetic mutation presented with behavioural variant FTD apart from one patient with a C9orf72 expansion who presented with PNFA.Fifty-eight patients with FTLD  and 20 patients with Alzheimer’s disease  were assessed consecutively over a 3-year interval via a tertiary Cognitive Disorders Clinic. All fulfilled consensus diagnostic criteria for a syndrome of FTLD (c memory  and furtSupplementary Table 1). This questionnaire recorded caregiver descriptions of patients’ symptoms and initially sought to capture any unexplained unpleasant physical symptoms more generally, before focusing explicitly on altered behavioural responses to pain or temperature variations. Questionnaire data were analysed off-line to determine the nature of any alteration in pain or temperature responsiveness and its directionality (increased versus decreased), based on caregiver descriptions of patients’ overt verbal and non-verbal behaviours. Chi-square tests were used to compare categorical differences in symptom prevalence and linear regression was used to compare differences in background demographic and neuropsychological measures between groups. In addition, we assessed for any correlation between pain and temperature symptoms and any alteration in hedonic processing in the domains of music and environmental sounds, as previously recorded for this patient cohort  developing since the onset of their illness  was acquired. In all cases, volumetric scans were assessed visually in all planes to ensure adequate coverage and to exclude artefacts or significant motion.At the time of questionnaire data collection each patient underwent volumetric brain MRI on a 3.0 T Siemens scanner using a 32-channel phased-array head coil. A sagittal 3D magnetization prepared rapid gradient echo TTo assess any relation between individual brain atrophy profile and development of pain and temperature symptoms, each patient’s brain magnetic resonance scan was reviewed by two experienced cognitive neurologists  while blinded to symptomatic and clinical syndromic status. In each case, the presence of relatively focal brain atrophy (disproportionate to more diffuse background atrophy) and the direction of any cerebral hemispheric asymmetry on visual inspection were recorded for the frontal, temporal and parietal lobes. Any apparent right:left directionality of atrophy was assessed for each lobar region using chi-square tests.www.fil.ion.ucl.ac.uk/spm) running under Matlab7.0®. Segmentation, normalization and modulation of grey and white matter images were performed using default parameter settings. Images were smoothed using a Gaussian full-width at half-maximum of 6 mm. To adjust for individual differences in global grey matter volume during subsequent analysis, total intracranial volume was calculated for each participant by summing grey matter, white matter and CSF volumes following segmentation of all three tissue classes. A study-specific group mean template brain image was created by warping all native space whole-brain images to the final DARTEL template and calculating the average of the warped brain images.Preprocessing of patients’ brain magnetic resonance images for VBM was performed using New Segment  and the C9orf72-associated FTLD  was modelled for the combined FTLD cohort and for the Alzheimer’s disease cohort: firstly, as a function of presence versus absence of any symptoms suggesting altered pain or temperature processing; and as a function of presence versus absence of symptoms for pain and for temperature separately. Participant age, total intracranial volume, Mini-Mental State Examination score  and syndromic group membership (where relevant) were included as covariates of no interest in the models. In addition, in light of recent evidence suggesting a distinct pathophysiological signature of P < 0.05 after family-wise error (FWE) correction for multiple voxel-wise comparisons. Maps were first assessed after correction over the whole brain volume, to determine any associations that emerged without taking the evidence of previous studies into account. Maps were next assessed after correction within a regional small volume of interest, taking account of previous evidence and our specific anatomical hypotheses: this single anatomical small volume combined structures in both cerebral hemispheres consistently identified as critical for interoceptive and homeostatic processing of pain and temperature in the healthy brain, namely, insular cortex and thalamus .Statistical parametric maps of regional grey matter volume correlating with pain and temperature symptoms were assessed using two prescribed criteria, each thresholded at Supplementary Table 2.Characteristics of the patient cohort are summarized in P < 0.05 all comparisons): accordingly, behavioural variant FTD and semantic dementia phenotypes were relatively over-represented in the symptomatic FTLD subgroup  cases; whereas these symptoms were recorded less frequently (2/5 cases) for patients with MAPT mutations.Symptoms suggesting abnormalities of pain and/or temperature processing were reported in 31/58 patients with FTLD (53% of the whole FTLD cohort) and in 9/20 patients with Alzheimer’s disease (45% of the Alzheimer’s disease cohort). In both FTLD and Alzheimer’s disease cohorts, altered responses to temperature variations were more frequently reported than altered responses to pain. While patients with FTLD  and Alzheimer’s disease  commonly had altered responses both to pain and temperature, only patients with FTLD  had altered pain responses alone. Within the FTLD cohort, symptoms suggesting altered pain or temperature processing were statistically significantly more common in the behavioural variant FTD group  and semantic dementia group  than in the PNFA group  revealed a diverse phenomenology of altered pain and temperature experience among patients in the symptomatic cohort. Pain symptoms were variably reported as arising from the external environment or from within the patient’s own body; while temperature symptoms were mainly described as subjective discomfort relative to the ambient environment and only occasionally referred to thermal touch per se. Symptoms varied widely in intensity and frequency. Both increased responsiveness and decreased responsiveness to pain and temperature variations were described, as well as responses that were variably increased or decreased within or between modalities. Within the temperature modality, patients more often developed a dislike of cold (rather than warm) environments. The directional preponderance of altered pain and temperature responsiveness varied between syndromic groups: within the behavioural variant FTD group, decreased responsiveness and increased responsiveness to pain and temperature variations were equally frequent ; whereas increased responsiveness was more commonly described within the semantic dementia group , the PNFA group  and the Alzheimer’s disease group .Caregiver reports (P < 0.01) greater impairment of face memory than the non-symptomatic FTLD subgroup; the subgroups within each disease cohort were otherwise similar overall (P = 0.03) but not environmental sounds (P = 0.8).When neuropsychological profiles in the patient subgroups within the FTLD and Alzheimer’s disease cohorts were compared according to the presence or absence of pain and temperature symptoms, the symptomatic FTLD group showed significantly . Focal temporal lobe atrophy was frequent in all three FTLD syndromes within the symptomatic cohort but concentrated (as anticipated) in the semantic dementia subgroup. These findings were further corroborated in the VBM analysis mapping overall grey matter atrophy profiles in FTLD subgroups with and without pain and temperature symptoms versus healthy controls . Disproportionate temporal lobe atrophy was also frequent in patients with Alzheimer’s disease and pain and temperature symptoms; however, in contrast to the FTLD cases, none of these Alzheimer’s disease patients exhibited asymmetric temporal lobe involvement nor was there any temporal lobe predilection for symptomatic versus non-symptomatic Alzheimer’s disease cases.Visual review of individual patient MRI scans (summarized in P < 0.05FWE) at the level of the whole brain. However, within the combined FTLD cohort, the presence of any alteration in pain or temperature responsiveness was significantly associated with atrophy of right mid insula  when thresholded at P < 0.05FWE after correction within the prespecified anatomical region of interest; no significant grey matter associations were identified for pain symptoms or for temperature symptoms separately, at the prescribed threshold. In the separate VBM subanalysis of patients with C9orf72 expansions contrasted with other FTLD patients showing altered pain or temperature responses . No other grey matter associations were identified at the prescribed significance threshold.Regional grey matter correlates of pain and temperature symptoms from the VBM analysis are summarized in esponses , symptompost hoc exploratory analysis of the VBM data thresholded more leniently at P < 0.001 uncorrected for multiple voxel-wise comparisons over the whole brain. At this more lenient threshold, additional regional grey matter correlates were observed . Pain and temperature symptoms in the combined FTLD cohort and in the subgroup not associated with C9orf72 mutations were additionally associated with atrophy of right anterior temporal cortex; while temperature symptoms (but not pain symptoms) in the FTLD cohort were associated with atrophy of right mid-insula . Pain and temperature symptoms within the smaller Alzheimer’s disease cohort were associated with grey matter atrophy in left angular gyrus  using this relaxed criterion.To identify any less robust but potentially relevant neuroanatomical associations of pain and temperature symptoms in the patient cohort, we performed a separate C9orf72 mutations. Patients with Alzheimer’s disease exhibited similar symptoms in a somewhat lower proportion (45%) of cases. The directionality of symptoms (heightened versus diminished responses to pain and temperature) varied across the cohort but was also modulated by syndrome: increased responsiveness to pain or temperature variations was most often reported in the semantic dementia, PNFA and Alzheimer’s disease groups whereas decreased responsiveness was most often associated with behavioural variant FTD, again consistent with previous evidence  temporal lobe atrophy in individual patients with FTLD, as anticipated from previous work and consistent with the more severe face processing deficit in this FTLD subgroup  here was corroborated both by inspection of individual magnetic resonance brain images and the relaxed VBM analysis, and chimes with previous evidence implicating this region in non-verbal sensory semantic (including pain and somatic) processing  and at the same time, richly invested with subjective emotional, mnestic and semantic associations . As such, pain and temperature provide a paradigmatic illustration of a key principle of cortical neurobiology , 2009 anThis model does not exclude the possibility of additional loci  at which neurodegenerative pathologies might degrade pain and temperature signals, with potential consequences for cortical elaboration of these signals . RelatedCorf72 mutations. Perhaps more surprisingly, our findings suggest that similar symptoms  are not uncommon in patients with Alzheimer’s disease and have probably been under-recognized. Aside from any potential value in diagnosing dementia syndromes, improved understanding of patients’ experience of pain and temperature holds clear practical implications for management. The present findings go beyond the simple assumption that cognitive impairment hampers communication of distress—the data suggest that underlying brain mechanisms of pain and temperature processing may be altered in dementia. Patients with dementia may be at increased risk of undetected illness or injury and potentially vulnerable to hypothermia, or other homeostatic derangements. The recognition that homeostatic processing may be significantly degraded in these diseases paves the way for developing strategies to ensure that patients are neither subjected to futile diagnostic procedures nor denied medical attention simply because they are uncomplaining.From a clinical perspective, the present work provides a framework for understanding an important category of symptoms that has been under-emphasized in neurodegenerative disease. Our findings underline the prevalence of pain and temperature symptoms across the FTLD spectrum and suggest a syndromic preponderance characterized by blunted versus heightened responsiveness to pain and temperature signals in behavioural variant FTD and semantic dementia, respectively. This syndromic association in turn may suggest a candidate mechanism for the somatization, hypochondriasis and abnormal illness behaviour that these patients frequently exhibit, particularly in the setting of focal right temporal lobe atrophy , future work should code symptom frequency and intensity for parametric correlation with other disease measures. It will also be important to explore patients’ conceptualization of interoceptive signals, as this might yield further signatures of disease [for example, delusional elaboration in association with utations .


To assess short and longer-term outcomes of ultrasound-guided glenohumeral corticosteroid injections for adhesive capsulitis.A mixed prospective and retrospective study designDepartment of Physical Medicine and Rehabilitation, Spaulding Rehabilitation Hospital, Department of Orthopaedic Surgery, Brigham and Women’s Hospital, between June 2011 and July 2012.Using medical records, we first retrospectively identified patients who had received ultrasound-guided injections of lidocaine and triamcinolone for adhesive capsulitis We then assessed short-term follow-up outcomes (within 3 months of procedure) using medical record review and phone interviews. Longer-term follow-up (at least 3 months from the procedure) outcomes were determined by mailings and phone calls. Average and worst shoulder pain scores were measured on a visual analog scale. Shoulder ROM was measured in forward flexion, isolated abduction, and external rotation.Patients presented an average of 5.1 (SD=4.1) months after onset of symptoms. Within three months of the injection, 55.9%  of patients reported greater than 75% pain relief and 44.1%  of patients reported greater than 75% ROM improvement. The percentage of patients who improved increased with increased duration of follow-up. At short-term follow-up , average pain decreased from 5.6 (SD=2.2) to 3.0 (SD=1.8) (p ≤ .001) and worst pain decreased from 7.8 (SD=1.2) to 4.3 (SD=3.2) (p ≤ .001). At longer-term follow-up , average pain decreased to 1.9 (SD=1.9) (p ≤ .001) and worst pain decreased to 2.9 (SD=2.3) (p ≤ .001).A majority of patients had significant pain reduction and functional improvement after an ultrasound guided glenohumeral corticosteroid injection for adhesive capsulitis. Our patients experience the majority of their pain and functional relief within the first three months after an ultrasound-guided corticosteroid injection with continued increase in relief in the longer-term. Adhesive capsulitis is a debilitating shoulder condition of unknown etiology. In addition to pain, there is a significant loss of active and passive range of motion. Adhesive capsulitis most commonly affects women of ages 40–60 ,2. DiabeTreatment options for adhesive capsulitis include non-steroidal anti-inflammatory drugs, physical therapy, manipulation under anesthesia, dilation or distension of the shoulder joint, arthroscopic capsular release, and oral or intra-articular corticosteroids. The joint capsule is the site of pathology in adhesive capsulitis and glenohumeral corticosteroid injections target this location. Glenohumeral injections performed without image-guidance can be inaccurate and fail to be consistently placed in the glenohumeral joint –13. HencWe assessed short-term and longer-term effects of ultrasound-guided glenohumeral corticosteroid injections on shoulder pain and range of motion. We also assessed factors associated with better outcomes after an ultrasound-guided corticosteroid injection for adhesive capsulitis.Ethics approval for this study was obtained from the Institutional Review Board at our institution.Electronic billing records were used to retrospectively identify patients who had received an ultrasound-guided, intra-articular corticosteroid injection for adhesive capsulitis from June 1, 2011 to December 31, 2012. One of three shoulder/sports fellowship-trained physicians  made the diagnosis of adhesive capsulitis based on presence of shoulder pain and limitation in active and passive range of motion, and shoulder x-rays to rule out osteoarthritis.There were 67 potential subjects ascertained from our billing records. Patients were excluded if they were either non-English speaking (n=4) or did not present for follow-up within 3 months of the injection (n= 12). Four patients received a second injection for reasons such as a shoulder trauma since the first injection or because of incomplete relief from the first injection. These patients were excluded to avoid bias in our results. No patients reported major complications due to an injection.Our final patient population included 47 patients/51 shoulders . Of thesAll injections were performed by a single physician (NJ). Patients were injected using a posterior, lateral to medial, approach while seated or in lateral decubitus. Ultrasound guidance was performed using a 5.5 megahertz curved linear array or a 13–8 megahertz linear transducer. A 20, 21, or 22 gauge spinal needle was used to inject approximately 4 milliliters of 2% or 1% lidocaine, and 40 milligrams of triamcinolone acetonide  into the glenohumeral joint. After the injection, patients were referred to physical therapy or asked to begin a home exercise program in 2–4 weeks so as to allow for pain relief prior to initiation of stretching exercises that are otherwise painful in adhesive capsulitis.Patients reported average and worst pain during 2 weeks prior to the injection using the visual analog scale (VAS) of 0 to 10. Subjective shoulder value (SSV) 16 was assessed on a scale of 0 to 100, where 100 represented a completely normal shoulder that has no pain and is fully functional and 0 represented one that has the worst possible pain and function. Range of motion was measured in forward flexion, isolated abduction, and external rotation in neutral by the attending physician in all cases (NJ).Patients were followed up at two time points – within 3 months of the injection (short-term) and at greater than 3 months since the injection (longer-term). Patients were routinely scheduled for a follow-up visit in clinic within 3 months (n=35) when they completed an injection questionnaire that included average and worst pain scores and SSV. ROM was measured by the attending physician at this visit. Pain scores, SSV, and ROM measures were then retrospectively retrieved from electronic medical records. As part of this study protocol, patients not yet due for an in-clinic follow-up visit at the start of the study (i.e. less than 3 months after the injection) were called by phone to assess pain scores and SSV (n=12).Longer-term follow-up was defined as a follow-up conducted 3 or more months after the corticosteroid injection. A total of 36 patients available for longer-term follow-up were administered a telephone questionnaire where they were asked a structured series of seven questions pertaining to the pain and function of their affected shoulder(s) that included average and worst pain scores and SSV. The questionnaire also assessed the length of time to obtain >75% pain relief and >75% range of motion improvement (range of motion was not measured objectively by the patient or provider in longer-term follow-up). Basic descriptive statistics were performed with means and standard deviations for continuous variables and number and percent for categorical variables. Race/ethnicity was defined as a dichotomous variable – white and non-white. Paired t-tests were used to compare continuous variables  between paired groups of observations. Linear regression was used to identify the association between changes in shoulder outcome measures such as average pain, worst pain, and ROM and factors such as age, gender, race, duration of pain in months, and presence of diabetes, hyperthyroidism or hypothyroidism, or hypertension. Patient characteristics used for regression variables were selected based on prior studies showing possible associations with adhesive capsulitis. Statistical analysis was performed using Microsoft Excel 2007 for Windows.The mean short-term follow-up duration was 2.1 (SD=2.7) months. Significant improvements were found in pain scores for average pain and worst pain, range of motion measurements for forward flexion and isolated abduction in patients with short-term follow-up. Average pain decreased from 5.6 (SD=2.2) to 3.0 (SD=1.8) (p ≤ .001) and worst pain decreased from 7.8 (SD=1.2) to 4.3 (SD=3.2) (p ≤ .001). Forward flexion increased from 96.6 (SD=29.4) degrees to 128.2 (SD=19.6) degrees (p ≤ .001) and isolated abduction increased from 52.3 (SD=16.5) degrees to 83.0 (SD=16.1) degrees (p ≤ .001) .Improvements in subjective shoulder value and external rotation did not reach statistical significance in short-term follow-up. The mean longer-term follow-up duration was 10.4 (SD=3.7) months. There were significant improvements in subjective shoulder value, average pain, and worst pain as compared to their baseline values in longer-term follow-up. Average pain decreased to 1.9 , worst pain decreased to 2.9 , and subjective shoulder value increased to 73.3 .Unlike A majority of patients  achieved greater than 75% pain relief in the first three months after the injection and 44.1% (95% CI=27.4–60.8%) of patients self-reported greater than 75% range of motion relief within three months of the injection . Within Age, sex, diabetes/thyroid disease, and hypertension were not significantly independently associated with either short-term or longer-term outcomes of shoulder injections for adhesive capsulitis. There was a weak association between patients who self identified as white and improvements in longer-term pain outcomes. Patients identifying as white had an additional 31.1% improvement of average pain, additional 24.2% improvement in worst pain, and an overall 2.7 points greater improvement in worst pain score. This association was not observed for any of the short-term outcome measures. There was also a weak, but significant, association between duration of pain and change in external rotation  in short-term follow-up.We assessed short-term and longer-term outcomes of patients undergoing glenohumeral injections under ultrasound guidance for adhesive capsulitis. The results of this study indicate that patients with adhesive capsulitis generally experience rapid improvement in shoulder pain and range of motion outcomes after an ultrasound guided corticosteroid injection. Most patients experience improvements in pain and range of motion within 3 months of the injection. Further, smaller improvements are seen at longer-term evaluation.Ultrasound-guided injections accurately deliver corticosteroids into the glenohumeral joint –14,17. OSome randomized trials have shown that corticosteroid injections offer no significant improvement in pain improvement as compared with a control group by the end of their study periods , 22–30. To the best of our knowledge, there are no studies investigating the factors associated with better outcomes after corticosteroid injections for adhesive capsulitis. Our analysis of determinants of better outcomes in short-term and longer-term follow-up after glenohumeral injections was exploratory given the relatively small sample size. A longer duration of symptoms prior to injection was associated with a smaller change in external rotation range of motion during short-term follow-up. A possible explanation for this finding is that patients may already be in the second (freezing) phase of adhesive capsulitis if their presentation was delayed after the onset of symptoms. Hence, better range of motion improvement may potentially be achieved if the injection is performed earlier after onset of symptoms. Patients who self-identified as white also had better outcomes on some but not all measures. This finding needs to be replicated in larger studies to make definitive conclusions.Limitations of our study include the absence of a comparison group, such as a placebo group or a physical therapy only group because our study was not a randomized controlled trial. No patients in our study received unguided injections because ultrasound guidance is considered the best injection practice at our clinic. In addition, the limited sample size precluded identification of factors with modest effects on outcome. Also, the potential effect of other co-interventions such as physical therapy may have an impact on longer-term outcomes.In conclusion, patients experience significant improvements in shoulder function and pain after an ultrasound-guided, intra-articular corticosteroid injection for adhesive capsulitis, with most of the improvement occurring early on in the treatment timeline. Patients also report continued improvement in shoulder function and pain in the longer-term. Further investigation is needed to determine the predictors of better outcomes.


To evaluate the effect of Low Level Laser (LLL) application at the points of greatest pain in patients with chronic masticatory muscle pain.n = 10); patients received the LLL at the point of greatest pain, laser group II (n = 10); patients received LLL at pre-established points in the effected muscles and placebo group (n = 10). LLL and placebo were applied three times per week, for a total of 12 sessions. Mandibular mobility was examined, masticator muscles tenderness were assessed and PPT values were obtained. Subjective pain levels were evaluated using VAS. The measurements performed before the treatment and after the completion of the therapy. Descriptive statistics  Student’s t-test, Mann–Whitney U-test and paired-sample t-tests were used for analysis.A total number of 30  were selected after the diagnosis of MPDS according to the Research Diagnostic Criteria for Temporomandibular Disorder (RDC/TMD). The patients were randomly divided into three groups; laser group I (In both laser groups, there was a statically significant reduction in PPT values of the muscles, number of muscles without any pain on palpation increased significantly, mandibular movements’ ranges were improved. Laser group I demonstrated statistically better results than the Laser group II in all of the measured values. Plasebo group did not show any statistically difference in any of the measured values.LLLT can be accepted as an alternative treatment modality in the management of masticatory muscle pain and direct irradiation seems to effect better.ISRCTN31085, Date of registration 28/08/20145.Current Controlled Trials  Temporomandibular disorders (TMDs) are probably the most common cause of pain of non-dental origin in the maxillofacial area . The catLLLT, also known as ‘soft laser therapy’, has been investigated and used in the treatment of musculoskeletal pain syndromes for more than 3 decades. Numerous studies have demonstrated that LLLT effectively relieves pain and helps to re-establish normal function in patients with TMD –10. InteThe body of literature on LLLT is large, but the results of randomised and non-randomised clinical studies (including those with double-blind designs) are controversial. The protocols used in clinical studies have varied in terms of power intensity and location of laser application. Although a 632.8-nm neon-helium laser . and 660This study was performed at the Department of Prosthodontics, School of Dentistry, University of Istanbul, Turkey. Patients with orofacial pain who reported to the school’s primary TMD referral centre were selected over a period of approximately 13 months (September 2010 - October 2011). Sample selection was based on standardised clinical examination using the following inclusion criteria: 1) diagnosis of myofascial pain according to the Research Diagnostic Criteria for Temporomandibular Disorder (RDC/TMD) , 2) age This study was a double-blind randomised clinical trial (RCT). Participants were divided randomly into 3 age- and sex-matched groups: laser group I (LGI), laser group II (LGII) and the placebo group (PG). The randomizations of the patients were done with the help of a computer program. Patients were unaware of their group assignments. All participants underwent three treatment sessions per week for 1 month . An experienced prosthodontist who was blinded to the applied treatment evaluated the patients twice: 30 min before the first laser application session and 30 min after the last laser application session. Evaluation consisted of 1) functional examination, 2) pressure pain threshold (PPT) measurement, and 3) subjective pain intensity measurement.One week before the study began and during the course of the study, patients were asked not to take any analgesic or receive pain treatment. At the end of the study, patients in the PG received suitable treatment, such as an occlusal appliance or physical therapy.2 by applying 300 mW output power for 10 s.A continuous low-intensity semiconductor  was used for laser exposure. This device generates continuous radiation with regulated power. The single-probe laser device applies a laser diode generating infrared radiation of 820 nm wavelength. The beam diameter of the device is 6 mm and the probe has an angle of 45°. The energy intensity given to each muscle point was adjusted to 3 J/cmIn all groups, the laser was applied at a 2-mm distance. In LGI, LLLT was applied precisely and continuously to the greatest points of pain in the related muscle . In LGII, LLLT was applied in the same manner to three predetermined points on the masseter muscle  and three points on the temporalis muscle . In the PG, the laser device was switched on, but not programmed.Functional examination was based on Kurkcu’s official Turkish translation of the RDC/TMD . The samMasticatory muscle tenderness was assessed bilaterally by palpation. Mobility of the mandible on opening, lateral excursions, and protrusion was measured with a plastic millimetre-scale ruler. Alterations in the opening pathway were also evaluated. Patients were asked to report any pain during muscle palpation and mandibular movements, and this information was recorded using a verbal scale: 0, no pain; 1, mild pain; 2, moderate pain; and 3, severe pain.2) on the masticatory muscles. Compressions were performed using a 1-cm2 rubber tip. After performing a few test measurements on each participant’s lower arm, PPT values were obtained before and after treatment by applying pressure to the bilateral MS, MM, MI, and TA points. Patients were instructed to state immediately when the feeling of pressure became painful, at which time the pressure was stopped. Measurements were separated by 30-s rest periods.After calibration, an experienced prosthodontist used a dial algometer  to measure PPTs  were evaluated using a 100-mm visual analogue scale (VAS) before and after treatment.t-test for normally distributed parameters and the Mann–Whitney U-test for non-normally distributed parameters. Within-group comparison of normally distributed parameters was performed using paired-sample t-tests. The results were analysed using 95 % confidence intervals, with a significance level of p < 0.05.Under the assumption of a difference of one standard deviation in the primary endpoint among groups, an alpha level of 5 %, and a power goal of 80 %, 10 patients per group were determined to be necessary. For all statistical tests, NCSS 2007 and PASS 2008 Statistical & Power Analysis Software  were used. Descriptive statistics  were calculated for all variables. Quantitative data were compared using Student’s n = 10 per group). We identified no significant difference in age, sex, or pain duration among groups. Participants’ demographic characteristics are shown in Table Sixty-two of 814 examined patients with TMD of muscular origin fulfilled the inclusion criteria, and 33 of these patients agreed to participate in the study. Three enrolled patients did not attend appointments regularly and were excluded from the study. The study sample thus comprised 30 patients with TMD of muscular origin  allocated to the three study groups  at the beginning and end of the study. In clinical trials designed to investigate the efficacy of therapies aiming to resolve or reduce pain, the primary endpoint is reduction in pain intensity . For chrhttp://waltza.co.za/wpcontent/uploads/2012/08/walt_standard_for_conduct_of_randomized_controlled_trials.pdf]. Accordingly, an age- and sex-matched PG was included in the present study. The PG showed slight, but not significant, improvement in all tested parameters. These improvements could be explained by many factors. The most likely explanation involves the positive reactions of patients to technologically advanced laser treatment. Furthermore, palpation, which was a treatment component for all study subjects (including those in the PG), can relieve pain [In 2004, the World Association of Laser Therapy approved an agreement on the design of clinical studies employing LLLT; the use of a PG was established as a mandatory component [eve pain .The present study does have some limitations. The present study examined the effect of specific dose of LLLT on pain release and mandibular function and found out that active laser is superior to sham application. However the only the short-term effects were investigated. Additional research should be conducted in order to investigate the long-term effects of LLL in the treatment of TMD. Furthermore only one type of laser settings was used. Different light intensities might have produced different or better results. In order to be able to suggest a treatment protocol, a study population with greater sample size, followed-up for longer period and treated with different low-level laser parameter should be used.2, 300 mW output power) showed positive effects in managing pain caused by TMD and improving mandibular function due to its analgesic and myorelaxant effects. The localisation of laser application (at predetermined points vs. points of greatest pain), however, did not affect the results of LLLT. Further double-blind, randomised, placebo-controlled clinical research is needed to establish whether these findings have clinical relevance.Within the limitations of the present clinical trial, the tested type of LLLT (820 nm, 3 J/cm