Low-level laser therapy (LLLT) and extracorporeal shock wave therapy (ESWT) is applied in the conservative treatment of inflammatory plantar fasciitis, which is also a characteristic feature of spondyloarthritis (SpA) . We determined and compared the effectiveness of LLLT and ESWT using magnetic resonance imaging (MRI).  This study is a prospective, randomized, comparative, single-blind clinical study. Voluntarily followed 40 patients with the diagnosis of SpA and having pain at the heels at least for 6 months. Patients were divided randomly into two treatment groups. One group undertook 14 sessions of infrared Ga-Al-As LLLT, and the other group undertook 3 sessions ESWT. Feet functions of the patients were evaluated by American Orthopaedic Foot and Ankle Society (AOFAS) and Roles and Maudsley Scoring; VAS was evaluated for foot pain and function. In clinical assessment, disease activity was carried out by applying the BASDAI, the functional assessment was evaluated through the BASFI, and the patient quality of life was evaluated through the ASQoL; enthesitis was scored according to MASES assessment, performed before and at 1 month after treatment. The thickness of the plantar fascia was measured with MRI before and 1 month after treatment. p < 0.001). Only the VAS exercise score was superior to LLLT (p < 0.05). The thickness of the plantar fascia had decreased significantly on MRI in all two groups.  Compared with the pretherapy, progress in the feet function by AOFAS and Roles-Maudsley scoring and decrease in VAS levels were statistically significant in both groups ( The treatment of plantar fasciitis with LLLT and ESWT was more successful in pain improvement and functional outcomes with the dose, frequency, and duration used in our study. Plantar fasciitis (PF), a frequent cause of heel pain, is a chronic inflammatory disorder of the fascial enthesis. Mechanic, degenerative, inflammatory, and traumatic causes are defined as enthesopathy while inflammatory enthesopathy is called “enthesitis” –3. The cTypical pain, especially with the first few steps in the morning or after prolonged, present with a throbbing, burning, or piercing type of inferior heel pain. The treatment of plantar fasciitis is mainly conservative. Conservative treatment options include weight loss, Achilles tendon and fascia stretching exercises, daily physical activity arrangements, night supports, hot-cold treatments, ice massage, and soft and orthopedic walking shoes; viscoelastic ground still and physical therapy methods are used in chronic-resistant cases  , 8, 9.ESWT is the combination of the first letters of the words of Extracorporeal Shockwave Therapy . The posThe basic mechanism of low-level laser therapy (LLLT) is tissue stimulation. Biostimulant means accelerating the self-repair activity of living tissue. This effect is caused by the lymphatic drainage effect of radiation applied to tissues. The LLLT increases the permeability of the cell membrane and accelerates the fibroblast activity by increasing cell metabolism .Despite the increasing popularity of LLLT and ESWT, randomized controlled studies comparing the efficacy of treatment modalities are lacking. This study is aimed at comparing and determining the anti-inflammatory analgesic effect of LLLT and ESWT at a 1-month follow-up of plantar fasciitis in patients with spondyloarthritis.n) for each group was calculated to be 20 when divided into 2 groups with 95% confidence, 80% effect size, and 70% power . Study protocol of Celal Bayar University Faculty of Medicine Ethics Committee was taken with the decision No: 20478486; after the decision, patients were included in the study. Written informed consent was obtained from each patient. The study was conducted under the principles of the Declaration of Helsinki. Statistical power analysis was carried out before starting the study. The minimum number of people  2009, without the active disease , having at least 6 months of heel pain. The diagnosis was confirmed clinically by the physical examination finding of tenderness to palpation with local pressure at the origin of the plantar fascia on the medial tubercle of the calcaneus and with passive dorsiflexion of fingers. In our study, patients' pain  was evaluated with a visual analog scale (VAS). An indication of significant pain by a score of >5 for VAS (VAS for the first few steps in the morning and during exercise).The exclusion criteria were history of heel surgery, application of physical therapy methods, or local steroid injection in the heel within the last 3 months and any disease contraindicated to physical therapy. This was a prospective, laminated blocked randomized, comparative, single-blind, clinical study. The first treatment group was determined by the closed-envelope randomization method of the first patient meeting the criteria. Then two-block randomization was performed by minimization method stratification according to age and sex.2, and 830 nm wavelength infrared Ga-Al-As LLLT was applied to one group; 3 sessions in total of 10 Hz frequency 2.5 bar, and 2000 beat shock wave was applied once a week to the other group. LLLT, US therapy, and ESWT were performed by the same investigator using the BTL-5000 SWT combined device . All patients were included in the supervised exercise program.14 sessions of 50 mW, 10 Hz, 8 J/cmAmerican Orthopaedic Foot and Ankle Society (AOFAS) is a rearfoot score questionnaire that comprises nine questions to evaluate pain, function, and foot alignment. It has evaluated over a total of 100 points. A result of 0-69 bad, 70-79 moderate, 80-89 good, and 90-100 is considered excellent .Roles-Maudsley scoring system is a practical scoring method that measures the association of pain on the extremity with activity. The pain is scored as excellent-good-medium and bad .Pain intensity during exercise and morning first step was measured on a 100 mm visual analog scale (VAS). The endpoints of the scale were determined by no pain at 0 mm and unbearable pain at 100 mm .ASQoL is a scale that questions the quality of life of patients by giving yes-no answers to each question out of 18 questions. The sum of yes gives the score. Lower scores indicate better quality of life .BASDAI is an index of disease activity. There are 6 questions about fatigue, spinal and peripheral joint pain, compression sensitivity, and morning stiffness. On the 10 cm horizontal VAS scale, a value of 0 to 10 is determined in the first five questions, and the average of these two questions related to morning stiffness is averaged and the first 4 questions are summed and divided by 5 to produce 0-10 points. A score of 4 or more indicates active disease .Bath Ankylosing Spondylitis Functional Index (BASFI) consists of 10 questions, and each question is given a score of 0-10. Eight of them are related to activities of daily living and two of them evaluate coping with daily life. BASFI's total score is calculated by averaging 10 questions .MRI was performed using a SIGNA_ HDXT 1.5 Tesla MRI system  before and 1 month after treatment. The maximum thickness of the proximal plantar fascia where it attaches to the calcaneus was measured using electronic calipers on fluid-sensitive MRI sequences. After all the patients had completed the therapy, the pre- and posttreatment MRI scans were interpreted simultaneously by a radiologist (S.O.), who was unaware of the treatment groups.t-test for independent samples and the Mann–Whitney U test for categorical data. A p value of less than 0.05 was considered statistically significant.All analyses were performed using SPSS for Windows version 15.0 software . Continuous variables with normal distribution were shown as mean ± standard deviation. Categorical variables were shown as numbers. To compare the two groups for continuous variables, the groups were compared using the Demographical data and measurement results of the involved patients were presented in p < 0.05).The mean of Roles-Maudsley scoring, AOFAS posterior foot score, and VAS values calculated before and after treatment of the patients in the LLLT group is given in p < 0.05).The mean of Roles-Maudsley scoring, AOFAS posterior foot score, and VAS values calculated before and after treatment of the patients in the ESWT group is given in p > 0.05). In both groups, AOFAS posterior foot score was bad but increased to moderate after treatment.In p > 0.05). The decrease in the mean VAS value in the ESWT group during exercise was more in favor of treatment, and the difference was statistically significant (p < 0.05). Only the VAS exercise difference was superior to the LLLT group (p < 0.05).There was no significant difference between the two groups in mean VAS score first steps in the morning (p < 0.05).In p < 0.05).In p > 0.05).In p > 0.05). The difference of plantar fascia thickness was slightly higher in the LLLT group compared to the ESWT group, but this difference was not statistically significant (p > 0.05).In p < 0.05). There was a statistically significant positive correlation between SpA disease duration and BASMI (p < 0.05). The correlation between plantar fascia thickness and BASFI and BASDAI was found to be moderately positive (p < 0.05). The correlation between the duration of plantar fasciitis and the pretreatment values of BASDAI was statistically significant and moderately positive (p < 0.05).In Plantar fasciitis is a chronic inflammatory disorder of the fascial enthesis. Enthesitis is a distinctive pathological feature of spondyloarthritis . The mosIn this randomized study, patients followed with SpA diagnosis and having heel pain at least 6 months, diagnosed with PF differentially by physical examination, and with symptoms that did not regress with first step conservative treatment are divided into two groups randomized.2; the patients were overweighted according to World Health Organization classification . The most important mechanical factor leading to plantar fasciitis is overweight [The mean of the BMI from the demographical data of the patients was 27.60 ± 5.05 kg/merweight . In a sterweight .The incidence of plantar fasciitis increases with age. Rudwaleit et al. performed a study with patients of AS and axial SpA. The mean age of patients with axial SpA was 36.1 ± 10.6 years, and the average age of onset of disease was 33.2 ± 10.5 . In our There are many physical therapy methods used in conservative treatment of plantar fasciitis but in the last years especially LLLT and ESWT have gained popularity in recent years .In the 2014 heel pain guide, LLLT indicated reduced heel pain and limitation of foot activity, and it was recommended for plantar fasciitis treatment at the level of C evidence . One of β and IL-6 and inflammatory cell inhibition than 100 mW [α play an important role in inflammation in SpA, a chronic inflammatory disease. Our study is aimed at showing that LLLT has an analgesic effect on neurotransmitter secretion such as serotonin, and additionally, it has an anti-inflammatory effect by reducing TNF-α levels. A similar dose (50 mW) has been applied in the studies and the correlation of the disease activity parameters with clinical improvement is consistent with the data in our study [In animal studies, different doses of LLLT were examined and 50 mW was found to be more effective on inflammatory mediators such as IL-1n 100 mW . IL-1 anur study .3 dose to enthesitis regions of 20 juvenile SpA patients with plantar fasciitis  and one month after treatment the pain level was evaluated by VAS. VAS level was significantly decreased (decreased from 6 to 1.3). As a result of this study, the anti-inflammatory, analgesic, and antiedematous effectiveness of LLLT were emphasized [Harjacek et al. applied LLLT Ga-Al-As with 2.5-3 J/mphasized . This stA large number of randomized controlled trials were done to investigate ESWT efficacy in the treatment of plantar fasciitis. Shock waves have local anti-inflammatory effects. It has been shown that shock waves used in wound healing increase new vessel formation, regeneration, and create an antimicrobial environment .p = 0.001). We found ESWT superior to LLLT when we compare the two groups (p = 0.011).In a meta-analysis published in 2013, it was stated that ESWT had an effect on pain and function in tendinopathies and no side effects were seen. However, there is no complete and standard consensus on the implementation protocol of ESWT. In the treatment of chronic plantar fasciitis, ESWT decreased pain scores and its effect was reported to last for 12 months. ESWT is reported to be useful as a safer and more effective method in chronic cases . The patCosentino et al. investigated the efficacy of ESWT for calcaneal enthesopathy in 60 patients with heel pain and observed a significant decrease in VAS. Pain scores at rest and during activity 1 and 3 months after treatment. Changes in the entophyte structure were evaluated by ultrasonography, and no statistically significant difference was observed immediately after the treatment, but after 1 month there was a significant difference. He stated that ESWT may be effective in reducing pain, inflammation, edema, and altering entophyte morphology with this study .2, total 1,500 shocks, 4 sessions maximum painful point, and around 2 cm area) and evaluated with American Orthopaedic Foot and Ankle Society (AOFAS) and Roles-Maudsley scoring. It was found that it provided tissue healing with controlled inflammation and the effects started on the 3rd week after the treatment and the effects continued until one year. It has been reported that ESWT may be a noninvasive treatment that should be performed before surgery. In a study comparing ESWT and surgery, patients were called for a check-up after 3 weeks to assess treatment efficacy [In a study of patients with chronic plantar fasciitis, endoscopic surgery was compared with ESWT (0.22 mJ/mmefficacy . As we ap < 0.05). In a study investigating the effect of LLLT on pain and functionality in AS patients, individuals (n = 37) were divided into two groups; Ga-Al-As LLLT with a power of 30 mW, n = 18 and the other group (n = 18) underwent placebo LLLT application and VAS, BASDAI, BASFI, and ASQoL were used as scales. VAS (p < 0.05), ASQoL (p < 0.01), and BASDAI (p < 0.001) showed significant improvement at the end of treatment and at 2 months after treatment (p < 0.05). However, no statistically significant difference was found between treatment and placebo groups [Enthesopathy has been reported to be the most important factor affecting the quality of life in the inflammatory disease . In our o groups .In the study, comparing some variables with BASDAI, it was found that the presence of enthesitis reflected active disease and was higher in SpAs with enthesitis . We inclIn the study of Zhu et al., MRI was performed to monitor acute (after 24 hours) changes after a single session of 1500 shock wave pulsed ESWT treatment on the patients with chronic plantar fasciitis. Plantar fascia thickness and spur were examined with T1 sequence; the presence of calcaneal bone marrow edema and soft tissue edema were examined with T2 fat-suppressed sequence. After ESWT administration, soft tissue edema increased and plantar fascia thickness did not change in the acute period . This stp < 0.05). We thought that our patients were exposed to inflammation with prolonged duration of the disease and consequently increased joint movements.To investigate the relationship between SpA disease duration and patients' quality of life, disease activity, and metrological measurements, we looked at the correlation between ASQoL, BASDAI, and BASMI. We found that the correlation between SpA disease duration and BASMI was statistically significant and correlated positively with each other , but any correlation was found between disease duration and laboratory values . In our We found anti-inflammatory and analgesic effects of LLLT and ESWT statistically significant as it was the primary aim of our study. For the second aim of the study, we found significant results in both of the groups when we correlated the parameters of disease evaluation with clinical parameters. We did not observe any side effects of the treatment methods.We used clinical scales to evaluate the efficacy of LLLT and ESWT in the treatment of inflammatory plantar fasciitis. We found significant results in favor of treatment in both groups. These findings suggest that LLLT and ESWT may be beneficial in the treatment of plantar fasciitis in the dose, frequency, and duration we used in our study.In conclusion, we found that LLLT and ESWT significantly reduced the pain experienced with plantar fasciitis, providing clinical improvement.The present study had several limitations. The first and most important limitation was the short follow-up period. Second, the sample size of the study was relatively limited. We could not include a placebo group because of ethical concerns.With this study, we wanted to state that plantar fasciitis, which is common in patients with Spondilaoarthritis, can be treated with electrotherapy, and its effectiveness can be demonstrated by clinical and imaging methods.It is a study that may be important in terms of demonstrating the effectiveness of physical therapy methods with clinical and imaging methods.


Background: Pain is highly prevalent in Parkinson's disease and is associated with significant reduction in health-related quality of life. Subthalamic deep brain stimulation can produce significant pain relief in a subset of patients after surgery. However, the mechanism by which deep brain stimulation modulates sensory function in Parkinson's disease remains uncertain.Objective: To describe the motor and pain outcomes of deep brain stimulation applied to a series of patients with Parkinson's disease and to determine whether the structural connectivity between the volume of tissue activated and different regions of the brain was associated with the changes of these outcomes after surgery.Methods: Data from a long-term prospective cohort of 32 Parkinson's disease patients with subthalamic stimulation were combined with available human connectome to identify connections consistently associated with clinical improvement , pain intensity, and experimental cold pain threshold after surgery.Results: The connectivity between the volume of tissue activated and a distributed network of sensory brain regions  was inversely correlated with pain intensity improvement and reduced sensitivity to cold pain after surgery (p < 0.01). The connectivity strength with the supplementary motor area positively correlated with motor and pain threshold improvement (p < 0.05).Conclusions: These data suggest that the pattern of the connectivity between the region stimulated and specific brain cortical area might be responsible, in part, for the successful control of motor and pain symptoms by subthalamic deep brain stimulation in Parkinson's disease. Pain has a prevalence of 40–85% in Parkinson's disease (PD) patients , 2 and iStudies have demonstrated that the benefit of locally applied DBS to the STN might rely on the modulation of distant brain areas connected to the stimulation spot, through antidromic activation of neuronal somas, passing fibers, and afferent terminals from the cortex , 13. TheIn PD, there is an abnormal functional overactivity in pain processing regions, such as the insula, the cingulate cortex, and the prefrontal cortex , 11, andThis study presents original imaging results from a previous clinical study on the effects of DBS on non-motor symptoms in PD , 9 In thDetailed protocol has been previously published , 9. Briehttp://stnava.github.io/ANTs/) (http://www.lead-dbs.org)  . Once thdbs.org) . The VTAUsing VTAs as seed regions, structural connectivity estimates were analyzed using a normative structural connectome, which consists of high-density normative fibertracts based on 20 subjects . Global p < 0.05 and was then lowered according to the Bonferroni correction for multiple comparisons .Motor function (UPDRS-III), pain intensity (VAS), and sensory thresholds (HPT and CPT) were expressed as average ± standard deviation. Because the Kolmogorov–Smirnov test disclosed that the values did not have a normal distribution, Wilcoxon signed rank test was applied. Spearman coefficients were used to assess the variables' correlations. The level of statistical significance was set at The connectivity from VTAs was calculated for each patient. Structural connectivity strength was defined as the number of fiber tracts between VTA and the corresponding cortical area. This procedure resulted in R-maps with Spearman's rank-correlation coefficients for each voxel. The independent variable was defined as the VAS change (expressed in %), CPT change (CPT before–after), and DBS motor response (UPDRS-III in the off-medication before surgery–UPDRS-III off-medication/on-stimulation) 12 months after surgery. We did not include in the analysis the HPT because it did not change after the surgery.All 32 patients were included in the analysis. The mean duration of the disease was 15.4 ± 8.1 years, and the Hoehn & Yahr off-medication score was 2.7 ± 0.6. Preoperative UPDRS-III scores were 45.1 ± 12.3 in the off-medication and 16.8 ± 7.6 in the on-medication conditions. After STN DBS, the UPDRS-III scores in the off-stimulation/off-medication condition were 46.9 ± 13.4 and 23.9 ± 10.6 in the on-stimulation/off-medication condition (49% of improvement).p < 0.001). In those who remained symptomatic, there was significant reduction in pain intensity after surgery . One patient developed dystonic pain after surgery in the left arm. Comparing to baseline, STN DBS significantly decreased the CPT (reduced sensitivity to cold pain) after surgery in both hands . There were no changes in the HPT after surgery . No correlation was found between the change in pain intensity (VAS) and the CPT  and between VAS and the CPT with motor response to STN DBS (p > 0.05).Twenty-three patients (71.9%) had pain related to PD before the surgery. After STN DBS, eight patients (28.1%) remained with pain under their regular pharmacological treatment  or CPT changes  after surgery  and the right post-central gyrus  correlated negatively with VAS improvement (n = 23). Additionally, the right prefrontal cortex  correlated negatively with left CPT improvement (n=32). The left prefrontal cortex , the left insular cortex , and the left cingulate gyrus anterior division  correlated negatively with right CPT reduction, whereas there was a strong positive correlation with the left SMA  .There was no relation between the VTA intersection of the STN with VAS ( surgery . Using t= 0.002) . FinallyOur primary findings were that: (i) STN DBS alleviates pain intensity and reduces CPT 12 months after surgery in PD, but these changes differed between patients and were not correlated with each other; (ii) the VTA inside the STN does not explain the variance in pain change after surgery; and (iii) the pattern of the connectivity between the stimulated region and specific brain cortical areas may be responsible for this variance in outcome. This latter point reinforces the recent, growing evidence that, although the targets for DBS in neurological disorders are normally determined by specific anatomical regions , the ideal target may not necessarily be an anatomical structure itself but rather a structurally connected region. This has an obvious surgical targeting implication, but also highlights the importance of postoperative symptom-oriented programming in looking for the desired network within the same structural DBS target.n = 32) to explore the relationship between their sensory changes and the structural connectivity of the VTA with specific brain regions. We have found that the brain regions responsible for central pain processing  and between the sides (right and left), which limits us from drawing a more robust conclusion. In addition, due to the low alpha value after Bonferroni correction, many important correlations should be missed (type II error). Therefore, connectivity patterns that look at pain and other non-motor symptoms should be explored in larger studies. Second, the present study did not use a patient-based connectome, which would be preferable and more reliable, considering the possible anatomic variances in PD patients. Therefore, future studies using patients' connectomes should be performed to confirm our data. On the other hand, normative connectomes from healthy subjects have the benefit of large participant numbers, high-quality signal-to-noise ratios, and acquisition that involves operating unique high-power MRI scanners that are particularly designed for connectivity imaging. The connectome used in our study was created using the Gibbs global tracking algorithm , which hWe decided to use a broad brain map parcellation, which spans large parts of the cortex. Subsequently, a more specific brain area connected to the VTA could not be identified, and further studies using brain parcellation with smaller and more specific cortical areas would be helpful in this issue. Finally, another important point concerns the current models of calculating the VTA. The models assume that the whole VTA is activating the tissue, but, instead, the VTA represents the volume of the electrostatic field, where the axons and cell bodies receive electrons but may or may not be activated. This limitation is intrinsic to the VTA models and should be refined in future studies.Taking our findings and the literature review together, we can summarize that PD patients have higher pain prevalence and abnormal pain thresholds compared to controls and that the supraspinal areas involved in the nociceptive process are, overall, overactivated. Deep brain stimulation improves pain intensity and decreases sensitivity to cold pain and, in part, the amount of this change occurs through antidromic activation of the SMA  and is associated with the avoidance of activation of subcortical/cortical sensory circuitry areas. Metabolic, electrophysiologic, and functional studies on this matter could confirm our preliminary findings. Further clinical studies are necessary to define how to work together with the strengths of normative connectomes and connectivity data from individual patients.Anonymized data are available and will be shared upon reasonable request from any qualified investigator.cappesq.adm@hc.fm.usp.br. The patients/participants provided their written informed consent to participate in this study.This study was approved by our institution's ethics review board and registered in the clinical research database (# 0105/10). Ethical Committee: Comissão de Ética para Análise de Projetos de Pesquisa do HCFMUSP, Address: Rua Ovídio Pires de Campos, 225 – 5° andar – Prédio da Administração, Phone: 55 11 26 61 75 85, e-mail: RC: conception, organization, and execution of Research Project, execution and data analysis of Clinical Assessments, writing of the first draft and review and critique of Letter. MT, RG, VS, RI, and EB: organization of Research Project, execution of Clinical Assessments, review and critique of Letter. CF, DA, EF, and EB: organization and execution of Research Project, execution of Clinical Assessments, review and critique of Letter. DC: conception, execution, and supervision of Research Project, data analysis of Clinical Assessments, review and critique of Letter.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


To investigate the physiopathology of pain in chronic inflammatory rheumatic diseases (CIRDs), we assessed the prevalence of migraine and neuropathic pain in 499 patients with CIRDs. We studied 238 patients with rheumatoid arthritis, 188 with spondyloarthritis (SpA), 72 with psoriatic arthritis (PsA), and 1 unclassified. Migraine was diagnosed according to IHS migraine diagnostic criteria. Neuropathic pain was diagnosed when patients scored at least 3 on the DN4 questionnaire. Participants completed a validated self-assessment questionnaire. Migraine prevalence was 34% (165/484), and it was highest in PsA. Risk factors for migraine were a high level of anxiety, female sex, young age, and TNF-alpha inhibitor treatment (OR = 1.90 (1.13–3.25)). Besides, high disease activity was a risk factor in SpA. Blood CRP level was not significantly associated with migraine. Of 493 patients with CIRDs, 21.5% had chronic pain with neuropathic characteristics. Compared to the French general population, these patients had significantly higher prevalences of migraine (two-fold) and neuropathic pain (three-fold). This study showed that migraine and neuropathic pain frequently occurred in patients with rheumatic diseases. Therefore, upon reporting residual pain, these patients should be checked for the presence of migraine or neuropathic pain, despite adequate clinical control of rheumatic disease. Chronic inflammatory rheumatoid diseases (CIRDs) are a class of rheumatic diseases that includes rheumatoid arthritis (RA), spondyloarthritis (SpA), and psoriatic arthritis (PsA). The common feature of these diseases is that they cause inflammatory pain, which leads to functional disability. The current therapeutic objective is to achieve clinical remission, that is, the absence of pain, joint swelling, spinal stiffness, and biological inflammatory syndrome ,2. HowevThis study aimed to assess the prevalence of migraine and neuropathic pain in patients with CIRDs that were routinely followed in a Rheumatology department. We then compared these prevalences with those found in the general French population.Comité de Protection des Personnes Sud-Ouest et Outre-Mer II) (n°ID-RCB: 2017-A01655-48). All included patients provided written consent to participate in the study, in accordance with the Declaration of Helsinki.This study was approved by the local Ethics Committee  criteria for non-radiographic spondyloarthropathy or the peripheral ASAS criteria for peripheral spondyloarthropathy.We collected clinical and demographic data, including age, gender, tobacco use, type of rheumatic disease, and year of diagnosis. Disease activity was assessed with the Disease Activity Score in 28 joints, based on the erythrocyte sedimentation rate (DAS28 ESR), for RA or PsA, and with the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) for SpA and PsA. Functional disability was evaluated with the health assessment questionnaire (HAQ). Anxiety and depression were evaluated with the hospital anxiety and depression (HAD) questionnaire . All parTo ensure a maximal response rate, the questionnaire was deliberately simple; it was designed to be completed in less than 15 min for most of the patients. Validated questionnaires were used to limit the risk of bias. All participants first responded to the question: “Are you experiencing or have you experienced pain or headache during the last 3 months?”. Participants who responded “No” skipped the remainder of the pain questionnaire, and they completed the sections on anxiety, depression, and disease activity. Participants who responded “yes” completed specific surveys that covered headaches and other types of pain. After completion, the questionnaires were checked for accuracy by one of the investigators.Headaches. The first part of the questionnaire served to identify migraine; it included the diagnostic criteria for a strict migraine established in the third edition of the International Classification of Headache Disorders . This qup < 0.001). The self-administered DN4 questionnaire had a sensitivity of 81.6% and a specificity of 85.7% for an optimal cut-off score of 3 out of 7, being similar to those observed in the initial study using a clinician-administered version of the questionnaire [Other pain types. A grading system is recommended for neuropathic pain’s diagnosis . Althougionnaire . With thionnaire . Particiionnaire , which mThe primary objective of this study was to assess the prevalence of migraine and neuropathic pain in a sample of patients with inflammatory rheumatic diseases. Continuous data are presented as the mean ± standard deviation (SD) or the median and interquartile range (IQR), based on the statistical distribution. The assumption of normality was checked with normal probability plots and the Shapiro–Wilk test. Prevalence and categorical data are presented as the percentage and 95% confidence interval (95% CI).t-test. Alternatively, when the assumptions of parametric tests were not met, we used the Kruskal–Wallis test or Mann–Whitney test. The homoscedasticity hypothesis was verified with the Bartlett test. Categorical data were compared between groups with the chi-squared test or Fisher’s exact test. Binary variables of particular interest, like the presence/absence of migraine or pain, were evaluated with generalized linear models , which included these variables as response variables and estimated the odds ratios (OR) and corresponding 95% CI. Furthermore, we performed multivariable analyses to make simultaneous adjustments for variables that showed univariate significance or clinical relevance.Continuous parameters were compared between independent groups  with the ANOVA or student We compared the prevalences of migraine and neuropathic pain in our sample to those of the general population, based on Lanteri and Bouhassira studies. Differences were expressed as ORs, based on the Mantel–Haenszel method ,13.p-values and confidence intervals, without doing any mathematical correction for distinct tests comparing two modalities .All statistical analyses were performed with R and STATA software. All tests were two-sided, and the type I error was set at 5%. Following Rothman, we chose to report all the individual We included 499 patients with CIRDs . Patient characteristics are summarized in Nearly two-thirds of patients 313/488 (64.1%) reported that they experienced pain. Active disease was particularly prevalent in the PsA group (47%). In contrast, in the RA group, the mean DAS28 ESR (2.34 ± 1.23) corresponded to disease remission. The entire population showed low systemic inflammation  and low rates of fibromyalgia (6%) and depression (8%). Nearly half of the patients were treated with methotrexate or Tumor Necrosis Factor (TNF)-alpha inhibitors, particularly for RA and SpA, respectively.The prevalence of migraine was 34% (165/484) and the prevalence of strict migraine was 13.2% (64/484). These prevalences were higher in the PsA group. Parameters associated with a higher prevalence of migraine are shown in Female sex and a higher level of anxiety were always associated with migraine, regardless of the type of rheumatic disease. Younger patients had a higher risk of migraine in the entire population and in the RA group. High disease activity  was associated with the prevalence of migraine only in the SpA group. Systemic inflammation was never significantly associated with migraine. TNF-alpha blockade treatment was associated with a significantly higher risk of migraine . Other treatments were not associated with the occurrence of migraine. Among the 165 patients with migraine, 124 (75.2%) had HIT-6 scores above 55, which indicated that headache had an important impact on these patients. In addition, the prevalence of chronic migraine was very high (12%). We found no difference in the headache burden among the three CIRDs groups .p = 0.02). Active disease , and salazopyrine treatment (OR = 1.90. 95% CI: 1.05–12.7) were associated with a higher risk of neuropathic pain (p < 0.001) (neuropathic pain x migraine (strict and probable) interaction (p = 0.02). This interaction was highlighted by the higher DAS28 ESR scores observed in patients with neuropathic pain and migraine (2.98 ± 1.36) compared to patients without migraine or neuropathic pain (2.18 ± 0.93), patients with neuropathic pain but no migraine (2.26 ± 0.91), and patients with migraine but no neuropathic pain (2.21 ± 0.92). However, the neuropathic pain x migraine interaction was not a significant factor in the HAQ (p = 0.33), HAD anxiety (p = 0.74), PCS (p = 0.99), or HAD depression (p = 0.65) tests.Among 493 patients with inflammatory rheumatic diseases, 21.5% had chronic neuropathic pain characteristics. The intensity of pain was moderate (5.0 ± 1.5). Prevalence was significantly higher in the SpA group (26.7%) than in the PsA (19.4%) and RA (17.6%) groups (hic pain . Moreove< 0.001) . For actp = 0.96). The effects of age  on the prevalence of migraines were also similar between our patients  and the general population . The higher frequency of neuropathic pain in our sample compared to the general population was more dramatic among younger patients , but was not different between the sexes .Compared to the general population, our cohort showed significantly higher rates of migraine  and neuropathic pain , based on the Mantel–Haenszel method. Similarly, we observed significant differences in strict and probable migraine rates between the general population and our cohort, when we performed separate analyses, according to gender  and age . However, we found no significant difference in the effect of gender  on the prevalence of migraines between our patients  and the general population  and a three-fold increase in neuropathic pain prevalence (21.5%) compared to the general population. The prevalence of migraines was highest in patients with PsA and the prevalence of neuropathic pain was highest in patients with SpA. The migraine prevalence was also higher in patients treated with TNF-alpha inhibitors and in patients with RA accompanied by high inflammation.Previous studies have suggested that migraines were linked to CIRDs ,23. We hWe found that, among patients with RA, the use of TNF-alpha inhibitors was associated with an elevated risk of migraine. This result was quite surprising, because TNF-alpha has been shown to participate in the physiopathology of migraine, and thus, blocking it should, theoretically, reduce the frequency of migraines. There are two potential explanations for our findings. First, patients who used TNF-alpha inhibitors had highly active disease, and our results tended to show that high disease activity was associated with migraine occurrence. Alternatively, this effect might be a paradoxical effect; for example, TNF-alpha inhibitors aggravated psoriasis, when they should have improved it. Moreover, Soubrier et al. previously described neurological symptoms in patients treated with TNF-alpha inhibitors, particularly etanercept . More reWe found that, in our cohort, sulfasalazine treatment was clearly associated with a two-fold higher risk of neuropathic pain compared to the general population. Some cases have been described previously, where patients treated with sulfasalazine experienced burning in the extremities, particularly the soles of the feet, related to neurotoxicity, peripheral neuropathy, or axonal neuropathy ,29,30. TIt is important to note that neuropathic pain has been shown to be associated with a more severe disease course in RA. Indeed, a recent study showed that the probability of remission was very low in patients presenting neuropathic pain . The samThe main limitation of this study was that the patient sample was not highly representative of the population of patients with rheumatic disease. In most participants, the disease was well controlled, with a low disease activity and a low CRP level. This potential bias might be explained by the time required to complete the entire survey, on average between 15 and 30 min, including the physician-administered and self-administered questionnaires. This consultation time for completing the survey might only have been carried out with patients that were essentially well. In patients with high disease activity, the consultation time was mainly used to achieve remission by changing treatments, administering articular corticosteroid injections, and taking blood samples, rather than examining patients for the presence of migraine, neuropathic pain, or other comorbidities. However, currently, remission is the rule in rheumatic disease management; thus, the majority of patients had well-controlled rheumatic disease. Another limit was the absence of a contemporary control group. Although we had the opportunity to compare the prevalence of migraine and neuropathic pain to the results from studies conducted in large and representative samples of the French general population, these studies were conducted more than 10 years earlier.In conclusion, this study found a high prevalence of migraine and neuropathic pain in a sample of patients with rheumatic disease. This finding should raise the awareness of the value of examining patients with CIRDs accompanied by residual pain for the presence of migraine or neuropathic pain, despite adequate clinical control of the rheumatic disease.


It is unclear whether regional anesthesia with infraclavicular nerve block or general anesthesia provides better postoperative analgesia after distal radial fracture fixation, especially when combined with regular postoperative analgesic medications. The aim of this study was to compare the postoperative analgesic effects of regional versus general anesthesia.n = 26) or regional anesthesia . Numerical rating scale pain scores, analgesic consumption, patient satisfaction, adverse effects, upper limb functional scores , health related quality of life (SF12v2), and psychological status were evaluated after surgery.In this prospective, observer blinded, randomized controlled trial, 52 patients undergoing distal radial fracture fixation received either general anesthesia (p ≤ 0.001 at rest and with movement). Morphine consumption in the post-anesthetic care unit was significantly lower in the regional anesthesia group (p<0.001). There were no differences in oral analgesic consumption. Regional anesthesia was associated with lower incidences of nausea (p = 0.004), and vomiting (p = 0.050). Patient satisfaction was higher in the regional anesthesia group (p = 0.003). There were no long-term differences in pain scores and other patient outcomes.Regional anesthesia was associated with significantly lower pain scores both at rest and with movement on arrival to the post-anesthetic care unit; and at 1, 2, 24 and 48 h after surgery  on 9th February 2017.Before subject enrollment, the study was registered at ClinicalTrials.gov ( Distal radial fracture fixation is a commonly performed orthopedic surgery. It is usually associated with moderate pain, but can sometimes also result in severe postoperative pain. Poor postoperative pain control would interfere with rehabilitation, delay recovery, and adversely affect outcomes , 2. DistRegional anesthetic nerve blocks have been shown to reduce acute postoperative pain, opioid consumption, improve patient satisfaction, and shorten postoperative stay –6. HowevWe performed a randomized controlled trial to compare the acute postoperative analgesic effect of RA with ultrasound guided infraclavicular nerve block versus GA plus local anesthetic would infiltration for distal radial fracture fixation. This was conducted with the use of regular postoperative analgesic medication. We also looked at longer-term secondary outcomes including chronic pain, upper limb functional scores, health related quality of life, and psychological well-being at 3 and 6 months after surgery. We hypothesized that RA together with regular postoperative analgesic medication would improve acute postoperative pain control after distal radial fracture fixation.clinicaltrial.gov prior to patient recruitment on 9th February 2017 (NCT03048214). Written consent was obtained from all patients participating in the trial.This study was conducted in a tertiary university hospital in Hong Kong, China. It was approved by the local university’s Institutional Review Board (UW 16–005), and registered at This was a prospective, observer blinded, randomized controlled trial. Patients aged between 18 and 80 years old with an American Society of Anesthesiologist (ASA) physical status of I-III scheduled for distal radial fracture fixation  were eligible. Exclusion criteria included surgery involving more than fixation of one affected arm; allergy to analgesic drugs including opioids, non-steroidal anti-inflammatory drugs (NSAIDs), local anesthetic drugs, and paracetamol; presence of chronic pain condition; chronic opioid user; alcohol or substance abuse; impaired renal function  ≥1.7, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) over 100 U/L; pre-existing neurological or muscular disorders; psychiatric illness; impaired mental state; non-ambulatory; pregnancy; local infection; coagulopathy or on anticoagulants (not including aspirin); or patient refusal.Eligible patients were randomly assigned to receive either GA plus local anesthetic wound infiltration (GA group) or RA with infraclavicular nerve block (RA group). Patients were randomized using a computer-generated random sequence. A statistician unaware of the nature of the clinical study prepared the sequence. Allocation was concealed in opaque envelopes and opened at the time of intervention by the attending anesthetist. Patients were aware of the type of anesthesia they were receiving. An investigator who was blinded from patient allocation collected the data from the patients. Patients were informed upon enrollment into the study not to tell the investigator collecting data which group they belonged to. The anesthetist who performed the anesthetic was aware of patient allocation, but was not involved in data collection.Sedative premedication was not prescribed. On arrival to the operating theatre, a 20- or 22-gauge intravenous cannula was inserted. Standard monitoring with pulse oximeter, non-invasive blood pressure, and three lead electrocardiogram (ECG) were applied before induction. Non-invasive blood pressure was measured at least every 5 min throughout the operation. Distal radial fracture fixation was performed in the hospital trauma list, which operated from 8.30 am to 16:30 pm on every weekday.2) of between 35 and 50%). Sevoflurane was titrated to 0.7–1.5 minimum alveolar concentration (MAC), and nitrous oxide was not used.Patients in the GA group were induced with intravenous propofol 1.5-3 mg/kg, fentanyl 0.25-2mcg/kg and atracurium 0.5 mg/kg. Patients were either intubated with an endotracheal tube or given a laryngeal mask airway as determined by the attending anesthetist. Additional doses of muscle relaxants were given as needed. GA was maintained with sevoflurane, air and oxygen  was given. Ondansetron 4 mg was given intravenously 30 min before the end of surgery. Sevoflurane was switched off after the inner layers of wound were closed. Local wound infiltration with 2 mg/kg of 0.5% levobupivacaine was given by the surgeon during wound closure. Reversal of muscle relaxation was achieved with neostigmine 50mcg/kg and atropine 20mcg/kg given intravenously. Subsequently, the patient was transferred to the post-anesthetic care unit (PACU) for 30 min to 1 h.Infraclavicular nerve blocks were performed under ultrasound guidance using a 22-gauge 50 mm or 100 mm Pajunk® needle for patients in the RA group. The decision whether to use a nerve stimulator was left to the attending anesthetist. Local anesthetic solution was made up of 10 ml of 2% lignocaine with 1:200,000 adrenaline plus 10 ml of 0.75% ropivacaine, made up to a total of 20 ml of local anesthetic solution. Fifteen to twenty milliliters of local anesthetic solution were deposited around the lateral, posterior, and medial cord of the brachial plexus under ultrasound guidance. All regional blocks were performed by a skilled specialist anesthetist or resident fellow under the direct supervision of a specialist anesthetist competent in performing ultrasound guided infraclavicular nerve blocks. Any immediate complications including paresthesia and vascular puncture were noted.Patients were sedated with propofol infusion during surgery by using the Marsh effect site model to keep the effect site concentration between 0.5–1.5mcg/ml. Propofol level was titrated to put the patients under light sleep where they could be easily aroused with verbal stimulation. Other sedative drugs or opioids were not used in this group. Intravenous paracetamol 1000 mg (15 mg/kg for patients under 50 kg) was given 30 min before the end of surgery. Anesthesia was considered inadequate if there was pain on pinching the surgical site using an artery forcep just prior to surgical incision. Patients with inadequate anesthesia were switched to GA according to protocol.Two milli-grams of intravenous morphine sulphate was given every 5 min until the numerical rating scale (NRS) pain score was less than 4/10 in the PACU. In the general ward, oral analgesics were given once oral fluid was allowed. Regular oral paracetamol 500 mg was given every 6 h for 3 days or until discharge. Oral dihydrocodeine 30 mg as needed every 6 h was prescribed for 3 days or until discharge. Patients were told that they could request dihydrocodeine if their NRS pain score was over 3/10.Oral fluid diet was allowed on postoperative day (POD) 0. The surgical team assessed for occurrences of postoperative surgical complications every morning and decided on patient suitability for discharge. Patients were assessed for possible complications related to the infraclavicular nerve block on POD 1, and they were reviewed again on POD 2 if complications could not be ruled out on the first assessment. Symptoms assessed included persistent paresthesia, tingling, abnormal sensation, and weakness. These assessments were made in the morning.NRS pain scores (0–10), where 0 represented no pain, and 10 represented the worse possible pain, was assessed at rest and on movement of the operated upper limb (attempted wrist flexion). These were performed on arrival to the PACU, and at 1, 2, 24, and 48 h after surgery. Frequency and dose of rescue morphine used in the PACU and oral dihydrocodeine used in the ward were recorded daily in the morning. Occurrences of adverse effects including nausea, vomiting, pruritus and dizziness were also recorded every day. The Aonos four-point scale (AFPS) for postoperative emergence agitation was recorded 30 min after arrival at PACU. Patient satisfaction with anesthesia (0–10), where 0 was the least satisfaction, and 10 was the most satisfaction possible, was assessed on POD 1.An investigator blinded to patient allocation conducted interviews at 3 and 6 months after surgery to collect the following information: NRS pain scores at rest and with movement (wrist flexion); patient satisfaction; health related quality of life measured using the Chinese version of SF12-v2 health survey , 14.The primary outcome was postoperative NRS pain score (0–10) with movement at 24 h after surgery. No suitable references for postoperative NRS pain scores at 24 h that could be used for sample size calculation was found. Based on a previous study on RA versus GA for hand surgery, the standard deviation estimate of the postoperative pain score from brachial plexus block was 2.86 . To deteP = 0.05. Intention to treat analysis was done. The statistical software used was IBM SPSS Statistics for Windows, Version 25.0 (IBM Corp. USA).Secondary outcomes included postoperative NRS pain scores at other time points (apart from 24 h postop), postoperative analgesic consumption, patient satisfaction, adverse effects, upper limb functional scores , health related quality of life (SF12v2), and psychological status (HADS score). Patient demographic and operative data were analyzed using Student’s t-test and Chi-square test. Postoperative NRS pain scores between the two groups were expressed as median (interquartile range) and compared using the Mann-Whitney U test, as the distribution of the pain scores was non-normal. To adjust for multiple statistical comparisons, post-hoc Bonferroni correction was also applied for comparison of median postoperative NRS pain scores between the two groups for all observed time points. Pain scores between 0 and 48 h and between 3 and 6 months after surgery were also expressed as area under curve (AUC) weighted by the corresponding time interval. The weighted AUC is equivalent to a time weighted average of the pain scores for the specified time interval and is of the same scale as the NRS (0–10). The difference in weighted AUC between the GA and RA groups was compared by the Mann-Whitney U test. Analgesic consumption, functional outcomes (PRWE and QuickDASH), patient satisfaction, health related quality of life and psychological status were analyzed using the Student’s t-test. Incidence of adverse effects was compared using the Chi-square test or Fisher’s exact test as appropriate. The critical value for statistical significance was Fifty-two patients in total (26 in each group) completed the study, which was conducted from May 2017 to January 2019. Fifty-five patients were assessed for eligibility, and 3 were excluded. Two patients declined to participate and 1 patient did not meet the inclusion criteria. All recruited patients completed the study for primary outcome measure and the results were used for analysis .Conversion to GA was required due to inadequate regional anesthetic block in 1 patient in the RA group. Intention to treat analysis was done. One patient from each group was lost to follow up at 6 months and were not included in the analysis for that time point. There were no significant differences between the two groups in patient demographics, duration of anesthesia, duration of surgery, and length of hospital stay (Table p<0.001 for pain at rest and with movement), 1 h (p<0.001 at rest and with movement), 2 h (p<0.001 at rest and with movement), 24 h (p = 0.001 at rest and with movement) and 48 h (p<0.001 at rest and with movement) after surgery (Table p < 0.05 after post-hoc application of Bonferroni multiple comparison correction. There were no significant differences between the two groups in NRS pain scores at rest and with movement (wrist flexion) at 3 and 6 months after surgery (Table p < 0.001 at rest and with movement). There were no differences in weighted AUC pain scores between the two groups from 3 to 6 months after surgery (Table Postoperative median NRS pain scores at different time points are shown in Table p < 0.001) (Table Consumption of rescue morphine in the PACU was significantly higher in the GA group (1) Table . Oral pa1) Table .Table 3p = 0.004) and vomiting (p = 0.050) after surgery (Table p = 0.035) (Table p = 0.003) and at 3 months  after surgery, but there were no differences at 6 months. There were no differences in the proportion of patients willing to repeat the same anesthetic technique (data not shown).There were no significant differences in the mean Aono’s score for emergence agitation in the PACU between the two groups Table . Patientry Table . There wry Table . No immery Table . SignifiThere were no differences in functional scores as measured by PRWE and QuickDash (Disability/symptom score) at 3 and 6 months after surgery Table . There wRA with infraclavicular nerve block was associated with reduced NRS pain scores at rest and with movement compared to GA plus local anesthetic wound infiltration on arrival to the PACU, at 1, 2, 24 and 48 h after surgery. Patients in the RA group used significantly less morphine in the PACU, but oral dihydrocodeine consumption was similar between the two groups. There were no differences in pain scores, upper limb functional scores (PRWE and QuickDASH), psychological status (HADS) or health related quality of life (SF12v2) at 3 and 6 months after surgery.Our results showed that RA was associated with better acute postoperative pain control compared to GA up to 48 h after distal radial fracture fixation. This is in contrast to the results from two previous randomized controlled trials conducted by Galos et al. and Rundgren et al. that compared RA versus GA for distal radial fracture fixation. In those 2 clinical trials, RA was not associated with overall analgesic benefit , 8. PatiThere are also other differences between our study and that of Galos et al. and Rundgren et al. that may have accounted for differences in our results. We examined both dynamic pain scores on movement of the upper limb and pain at rest, because we expected them to be distinctly different. In the clinical trials by Galos et al. and Rundgren et al., it is not clear whether pain scores assessed were at rest or with movement. The anesthetic technique was not standardized in the study by Galos et al. Differences in general anesthetic technique such as the choice of inhalational versus propofol total intravenous anesthesia can affect postoperative pain scores and opioid consumption –24. FinaIn this study, single shot infraclavicular nerve block was associated with improved postoperative analgesia for 48 h, which is beyond the pharmacological duration of the local anesthetic. This suggests that infraclavicular nerve block had preventive analgesic effects. Preventive analgesia is defined as a reduction in postoperative pain and/or analgesic consumption that persists longer than the clinical duration of the target drug  . We hypoWe evaluated the opioid sparing effects of RA versus GA. Morphine consumption in the PACU was significantly lower in the RA group compared to the GA group, which is similar to other studies comparing RA versus GA for upper limb surgery , 15, 18.We found no differences in longer-term outcomes between the 2 groups. This is in agreement with Galos et al. and Rundgren et al., which found no differences in pain, DASH, short musculoskeletal function assessment, PRWE, and EuroQol-5 Dimensions-3 Levels , 8. On tThere were some limitations in this study. The patients were not blinded, and this can introduce bias. However, it was not possible to blind the patients in this study. The investigators performing patient assessment and data collection were blinded, and bias does not appear to be a significant issue when the observer is blinded . AnotherOur study suggests that RA improves acute postoperative pain control compared to GA for distal radial fracture fixation. RA was also associated with higher patient satisfaction, and less nausea and vomiting. Preventive regular analgesic medication in combination with RA is probably important to improve postoperative pain control and prevent rebound pain.


Background: In patients with neuromuscular disorder, only little data of myalgia frequency and characterization exists. To date, only a weak correlation between pain intensity and pressure pain threshold has been found, and it remains enigmatic whether high pain intensity levels are equivalent to high pain sensitivity levels in neuromuscular disorders. Methods: 30 sequential patients with suspected neuromuscular disorder and myalgia were analyzed with regard to myalgia characteristics and clinical findings, including symptoms of depression and anxiety and pain- threshold. Results: A neuromuscular disorder was diagnosed in 14/30 patients. Muscular pain fasciculation syndrome (MPFS) without evidence for myopathy or myositis was diagnosed in 10/30 patients and 6/30 patients were diagnosed with pure myalgia without evidence for a neuromuscular disorder . Highest median pain scores were found in patients with pure myalgia and polymyalgia rheumatica. Pressure pain threshold measurement showed a significant difference between patients and controls in the biceps brachii muscle. Conclusion: Only a weak correlation between pain intensity and pressure pain threshold has been suggested, which is concordant with our results. The hypothesis that high pain intensity levels are equivalent to high pain sensitivity levels was not demonstrated. The International Organization for the Study of Pain (IASP) defines pain as “an unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of an injury. In 2013, the European Neuromuscular Centre (ENMC) care workshop noted that pain and fatigue are common symptoms in neuromuscular disorders (NMD) with a prevalence of 30–90%, present in all types of NMD, both in adults and children , myositiThirty patients  with suspected neuromuscular disease and myalgia were included in the study . All patIn addition to demographic information (age and gender), information on myalgia localization and pain character, adjusted according to the McGill questionnaire   were colPressure pain detection threshold (PPDT) (10 kg × 100 g) was determined by algesiometry in patients and controls. Measurements were performed using a Wagner Pain Test™ Model FPK Algometer  over the muscle belly of the biceps brachii muscle and the quadriceps muscle (rectus femoris muscle), both on the right and left side. The measurement was repeated three times over each muscle, and means were calculated for each muscle and patient. Histopathological analysis of muscle biopsies from either the biceps brachii muscle or the vastus lateral muscle were performed according to standard protocols . Geneticp = 0.05. The statistical tests chosen were predetermined by the size of the study group and the numerical range of values.Statistical analysis, calculation and visualization were performed using Prism 7 . The analysis of a possible relationship between two variables was carried out using linear regression. Analysis of correlation was carried out using multiple, unpaired t-tests. The p-value selection was based on the FDR . Significance was set to Data acquisition and analysis was performed in compliance with protocols approved by the Ethical Committee of the Martin Luther University Halle-Wittenberg . Written informed consent was obtained from all participants prior to study inclusion.Thirty patients with suspected neuromuscular disorder and myalgia were analyzed. The majority of patients  were diagnosed with a neuromuscular disorder: (I) four patients with clarified diagnosis: limb girdle muscular dystrophy type 1 B (LGMD1B) (n = 1), myoadenylate deaminase deficiency (MADD) (n = 1), anoctamin5- myopathy (n = 1) and mitochondrial myopathy without a genetic cause (n = 1); (II) six patients with myopthy ; (III) two patients with polymyositis and (IV) two patients with polymyalgia rheumatica (PMR). In this group of patients with neuromuscular disorders (n = 14), EMG showed myopathic changes in 5/14 patients, elevated CK was observed in 4/14 patients and myopathic changes in muscle biopsy was found in 12/14 patients. Ten patients were diagnosed with muscular pain fasciculation syndrome (MPFS) . Neither the EMG nor the muscle biopsy showed (performed in 7/10 patients) myopathic changes. CK elevation was shown in two patients. The third group consists of patients  with pure myalgia without any evidence for neuromuscular disorders. EMG, CK and muscle biopsy (performed in 4/6 patients) showed normal results.The majority of patients (30.43%) analyzed in this study described myalgia in two locations . The highest prevalence was shown in the lower and upper extremities. Unilateral pain was not reported. Interestingly, all patients described myalgia in the lower extremities. Furthermore, only one patient mentioned to have myalgia located in the facial area.Cramping pain was described by the majority of patients (40%), followed by burning (33%), stinging and dull (27%), drawing (16%), muscle ache-like (10%) and tension-like (10%) pain. One patient reported oppressive pain. 93% of patients described pain during physical activity; however, 73% of patients described muscle pain during resting without prior activity. Only 17% of patients reported that myalgia could not be triggered.The highest median VAS-score (8/10) was reported in the myalgia-group (n = 6), followed by VAS 7/10 in patients with muscular pain fasciculation syndrome (n = 10). The lowest median VAS-score (6/10) was found in patients with neuromuscular disorders (n = 14). There was no significant difference between the groups (p = 0.57).PPDT measurement showed a significant difference between patients and controls (p = 0.0130) in the biceps brachii muscle. However, the PPDT for the quadriceps muscle revealed no significant differences in patients and controls . The PPDThe majority of patients showed normal results in HADS evaluation  ; howeverIn the group of patients with a neuromuscular disorder, the median scores were 4 for anxiety and 6 for depression, in patients with muscular pain fasciculation syndrome 4.5 and 3.5 and in the myalgia group 8.5 and 5. There was no significant difference between the patients with higher scores for anxiety and depression in the different groups and between the pain scores.Based on several studies, it is already known that myalgia is a common feature in neuromuscular diseases ; howeverAll patients described myalgia in the lower extremities, 43% in two localizations. However, the highest prevalence was shown in the lower and upper extremities. Patients reported myalgia as cramping, burning and stinging/ dull . In 93%, myalgia was provoked by physical activity; however, in 73% during rest. However, the highest pain scores were reported in patients with pure myalgia and polymyalgia rheumatica and notes for depression and anxiety. In contrast, there were significant differences in pain threshold only in the biceps brachii muscle. p < 0 .001), and 15% in healthy controls (p < 0.001). Consistent with the results of our study, the mean pressure pain thresholds were lower in DM2 patients than in healthy controls; however, no differences were found in electric pain thresholds between DM2 and healthy controls [Thirty-four patients with genetically confirmed myotonic dystrophy type 2 (DM2), 28 patients with fibromyalgia (FMS), and 33 healthy controls were included into an explorative study, assessing qualitative and quantitative aspects of pain in DM2 . Pain prcontrols . Accordicontrols  revealedcontrols  showed tcontrols . The resIn a recent study, only a weak correlation between pain intensity and pressure pain threshold was found . This isIn 1/3 of the investigated patients, we found no pathological findings in neurological examination, histopathological investigation and additional diagnostics. According to their clinical manifestation of symptoms, muscular pain-fasciculation syndrome was diagnosed, suggesting that this disease should be considered as differential diagnosis more often. Recent studies have suggested only a weak correlation between pain intensity and pressure pain threshold, which is concordant with our results. The hypothesis that high pain intensity levels are equivalent to high pain sensitivity levels was not demonstrated. Furthermore, we did not find pathological evidence in neurological examination, histopathological investigation or additional diagnostics in 1/3 of the investigated patients. According to their clinical manifestation of symptoms, muscular pain-fasciculation syndrome was diagnosed, suggesting that this disease should be considered more often as a differential diagnosis. We are aware that this manuscript has its limitations, especially due to the small sample size. However, in times of increased genetic testing, e.g., next-generation sequencing (NGS), it is still difficult to find patients with myopathies, as they are still regarded as “rare diseases”. Furthermore, the study group was limited due to the fact that we performed electrophysiological studies such as muscle biopsy in nearly all patients (23/30). Upcoming studies need to investigate a larger patient cohort. This might provide more information about myalgia in patients with defined neuromuscular disorders.


Patients with shoulder pain were recruited in an outpatient rehabilitation clinic at the Third Affiliated Hospital of Sun Yat-Sen University from January 1, 2017, to June 30, 2018. These shoulder pain patients with or without limitation in joint movement can be included in the study. All of them received musculoskeletal ultrasound scanning. Demographic and imaging data including age, gender, duration of shoulder pain, pain side, and pathologies found by musculoskeletal ultrasound imaging were collected and analyzed. Patients were divided into three groups: <45 years (young group), between 45 and 60 years (middle-aged group), and >60 years (elderly group). The rates of various shoulder pathologies were evaluated and compared between the groups. P < 0.05). The rate of acromioclavicular joint degeneration was the highest in the elderly group followed by the middle-aged and young groups (P < 0.0167). The rate of supraspinatus tendinopathy and adhesive capsulitis in the middle-aged and elderly groups was significantly higher than that in the young group (P < 0.0167).  This study recruited a total of 346 patients with shoulder pain. There were more female (62.1%) than male patients (37.9%), with the largest number of patients in the 45-60 years of age group (40.5%). Forty-eight percent of patients had shoulder pain within a period of 3 months. A total of 380 shoulders were assessed using musculoskeletal ultrasound imaging. The occurrence rate of subacromial disorder (83.8%) was the highest. The rate of supraspinatus tendinopathy, acromioclavicular joint degeneration, and adhesive shoulder capsulitis varied significantly between age groups ( Musculoskeletal ultrasound can be a useful imaging tool in making an accurate diagnosis of shoulder pain. The occurrence rates of different shoulder pain pathologies in all age groups were thoroughly calculated in this study. More female and more subcoracoid disorder patients than western countries are attributed to repetitive lifting in daily life and work in this study. Correlations between these pathologies and their associated images can be a solid foundation for the development of artificial intelligence in diagnosing the cause of shoulder pain. Shoulder pain is a common complaint in rehabilitation and orthopedic outpatient clinics, with a prevalence rate between 2.4% and 26% . In geneIn the past, the diagnosis of shoulder pain is usually made according to medical history, clinical symptoms, and physical examination. However, uncertainty and wrong diagnosis may result . As a reThe major aim of this study was to observe the epidemiological pattern on the causes of shoulder pain in China. The occurrence rates of the different diagnoses of shoulder pain based on ultrasound images were calculated in all age groups. We hypothesize that the crucial information can be used as robust evidences in the future development of ultrasound diagnostic artificial intelligence that can be used in imaging interpretation of shoulder pain pathologies.st of 2017 to June 30th of 2018. A total of 346 patients with shoulder pain was recruited. Informed consent was assigned before participating in this study. The two main inclusion criteria were (i) shoulder pain with or without a joint range of motion limitation and (ii) patients were able to cooperate with the shoulder ultrasound examination apparatus. Patients with shoulder pain caused by spinal disease, shoulder joint fracture, trauma, tumor, systemic diseases, or post shoulder surgery were excluded from this study. Patients were divided into three age groups: the young group (<45 years), the middle-aged group (45-60 years), and the elderly group (>60 years). In addition, 12 healthy volunteers, 4 in each age group, were also recruited as controls and assessed by musculoskeletal ultrasound imaging.This study was conducted from January 1Patients were examined using the S-Nerve ultrasound system . The 6–13 MHz linear transducer was applied. Two physiatrists with at least 3 years of experience in ultrasound diagnosis and image interpretation performed all the examinations. They also received one week of ultrasound operating training together to reduce experimental bias. During the examination, when both physiatrists were confronted with controversial images, they discussed meticulously together to make the correct diagnosis. Musculoskeletal ultrasound technical guidelines were applied to examine the following physiological soft tissue structures : tendon Each patient was asked to sit on the revolving chair facing the physiatrist. When examining the LHB tendon, each patient was asked to place the arm in slightly internal rotation with the elbow flexed 90° and with palm up. The tendon of LHB between the greater and lesser tuberosities and its intra-articular course were examined, using the short- and long-axis planes. During the examination of the Sub tendon, each patient rotated the arm externally fixing the elbow joint on the iliac crest with the elbow flexed 90° and also with palm up. The short- and long-axis planes of the Sub tendon and its insertion on the lesser tuberosity were examined.When checking the A-C joint, the transducer probe was placed in the coronal plane over the joint that is formed by the acromion and clavicle. During the examination of the SupraS tendon, each patient's arm was placed in the modified Crass position . The SupAccording to the literature , the sigLHB tendinitis: thickened tendons and effusions in tendon sheaths, obvious pain when pressure was applied locally. Tendon of LHB dislocation: absence of biceps tendon in the bicipital groove. Bursitis, including SC bursitis and SA bursitis: focal or diffuse bursal thickening of more than 2 mm transverse thickness with associated hypoechogenicity with or without bursal fluid. Rotator cuff tendinopathy: may be accompanied with thickened tendons and with heteroechoic findings. Rotator cuff calcific tendinitis was diagnosed in the presence of hyperechoic calcific deposition within the tendon. Partial-thickness tear of SupraS: partial tear of the tendon fibers occurs either at the bursal or at the articular surface that appeared as a focal hypoechoic or anechoic defect not traversing the entire tendon. Full-thickness tear: discontinuity of the tendon fibers resulting in communication between the articular and bursal surfaces appearing as a hypoechoic or anechoic defect. Subacromial impingement: pooling of the SA bursal content just lateral to the acromion during dynamic shoulder abduction evaluation.A-C joint degeneration: ultrasound image showing evidence of A-C joint hyperosteogeny, rough cortex of the joint surface, and with or without joint effusion or capsular thickening. Adhesive capsulitis: decreased range of motion of G-H joint, and the possibility of glenohumeral effusion, and LHB tendon sheath effusion. In the present study, rotator cuff tendinopathy, rotator cuff calcific tendinitis, rotator cuff partial- or full-thickness tear, and subacromial bursitis were all regarded as subacromial disorders as suggested in the literature .P < 0.05.Clinical data of shoulder pain patients were collected, which included age, gender, duration of shoulder pain, painful side, and musculoskeletal ultrasound imaging of the affected shoulders. Data analyses were performed using the SPSS 17.0 software package. Data were described as mean and standard deviation. The rate of occurrence comparisons among the three groups  was performed using the chi-square test. The statistical significance was set as A total of 346 patients with shoulder pain were recruited in this study. The age ranged from 18 to 90 years. There were more female patients than male patients. The shortest duration of shoulder pain was only 6 days, and the longest duration was more than 10 years. The ratio of patients with a joint range of motion limitation was higher (80.2%) than without motion limitation (19.8%). Epidemiologic characteristics of patients with shoulder pain are summarized in A total of 380 shoulders were assessed using musculoskeletal ultrasound imaging. The most common pathology was due to subacromial disorders (83.8%), including rotator cuff tendinopathy 48.5%), calcific tendinitis 16.3%), partial- or full-thickness tear (15.5%), and subacromial bursitis (59.5%) . Ultraso6.3%, par8.5%, caln = 89), in the middle-aged group was 41.6% (n = 158), and in the elderly group was 35% (n = 133). The rate of occurrence in terms of percentages on common shoulder pathologies between the 3 groups was compared , calcified tendinitis, partial- or full-thickness tear, and subacromial bursitis. Ottenheijm et al. considered that subacromial disorders were the most common disorders affecting the shoulder . The ratStudies have reported that the prevalence of calcific tendinitis in the rotator cuff is between 6.8% and 54% in patients with shoulder pain . Eighty Musculoskeletal ultrasound is an accurate imaging tool in the diagnosis of subacromial bursitis . In the In the past, the diagnosis of adhesive shoulder capsulitis was based on clinical symptoms and physical examinations. Presently, literature has suggested that ultrasound imaging is the preferred imaging modality for the diagnosis of adhesive shoulder capsulitis . The occThere are some limitations in this study. This study was conducted in one tertiary medical center only. In future related studies, shoulder pain patients from multicenters will be recruited as well. In China, patients with shoulder pain can visit any department freely. For instance, patients with severe shoulder pain may visit orthopedic outpatient clinic first and receive surgical treatments subsequently. These patients may not have the opportunity to receive ultrasound imaging evaluation first.As a result, further collaboration with the orthopedic department is needed in order for the shoulder pain epidemiological data to be more comprehensive. Additionally, we did not do a reliability test before enrollment of the participants in this study.This study thoroughly explored the epidemiology and the ultrasonographic features of shoulder pain among all age groups in south China. Accurate shoulder pain diagnoses were made from musculoskeletal ultrasound images. This study has discovered some significant findings such as that the occurrence rate of subcoracoid bursitis was much higher as compared with other studies. The occurrence rates of subacromial bursitis and adhesive capsulitis were actually lower as compared with other literature. Since hundreds of patients were recruited, correlations between the diagnoses of shoulder pain and thousands of musculoskeletal ultrasound images can be made. These correlations can be used as solid evidences in the development of artificial intelligence in ultrasound imaging interpretation of shoulder pain pathologies. In all, ultrasound is a reliable tool that can be used in achieving an accurate diagnosis of shoulder pain and should be widely used in outpatient clinical settings.


Pain control after total knee arthroplasty has shown many advances; however, the optimal method remains controversial. The purpose of this present study is to assess the efficacy and safety of the addition of local infiltration analgesia to adductor canal block for pain control after primary total knee arthroplasty.2. Exclusion criteria were regional and/or neuroaxial anesthesia contraindications, the history of drug allergy involved in the research, neuropathic pain, as well as the chronic pain requiring opioid therapy. Seventy-two patients were divided into 2 groups randomly. Study group (n = 36) received both adductor canal block and local infiltration analgesia. Control group (n = 36) received adductor canal block alone. Primary outcome included postoperative pain score . The measures of secondary outcome included the knee range of motion, opioid consumption, the hospital stay length as well as the postoperative complications . All the analyses were conducted through utilizing the SPSS for Windows Version 20.0.This prospective randomized controlled research was conducted from January 2018 to June 2019. All the patients and their family members signed the informed consent forms, and this work was authorized via the ethics committee of Jinxiang Hospital Affiliated to Jining Medical College (JXHP0024578). Inclusion criteria were 55 years old or older, who possess the physical status I–III of American Society of Anesthesiologists, and the body mass index in the range of 18 to 30 kg/mThe results will be shown in Table 1The study will provide more evidence on the combination use of adductor canal block and local infiltration analgesia in the treatment of pain after the total knee arthroplasty.This study protocol was registered in Research Registry (researchregistry5832). However, postoperative pain remains a major complication, and pain control is an essential component of optimal care in surgical patients. Failure to provide adequate analgesia may affect physical rehabilitation, which is important to improve joint range of motion and promote satisfactory results. An extended period of postoperative inactivity may potentially increase medical costs, as well as aggravating the risk of thromboembolism, such as deep venous thrombosis and pulmonary embolism.,6Total knee arthroplasty (TKA) is commonly conducted to address the pain and functional disorder, which attends end-stage osteoarthritis and rheumatoid arthritis.–10 In comparison with the femoral nerve block, ultrasound-guided adductor canal block (ACB) can improve the strength of quadriceps femoris and is extensively utilized in the pain control after TKA. However, isolated ACB fails to provide adequate analgesia to the posterior knee. The duration of local infiltration analgesia (LIA) is short, which limits its clinical application. Barastegui et al reported that periarticular infiltration analgesia was effective and safe to decrease the perioperative pain 36 hours after TKA. Its effects will disappear with the passage of time, but it will not change the postoperative course of treatment, and will not affect the satisfaction of patients with short-term follow-up. Recent published studies have indicated that ACB in combination with LIA may achieve satisfactory effects, as well as an improved functional outcome.,14Several techniques have been introduced for the management of postoperative pain, including the epidural analgesia, patient-controlled intravenous analgesia, femoral nerve block, and multimodal cocktail periarticular injection.Currently, whether ACB combined with LIA is superior to isolated ACB remains controversial, due to the small number of the published articles examining the efficacy of each modality. The purpose of this present study is to assess the efficacy and safety of the addition of LIA to ACB for pain control after primary TKA. We hypothesize that ACB combined with LIA will provide better pain relief and in the immediate postoperative period compared with ACB alone.22.12. Exclusion criteria were regional and/or neuroaxial anesthesia contraindications, the history of drug allergy involved in the research, neuropathic pain, as well as the chronic pain requiring opioid therapy.This prospective randomized controlled research was conducted from January 2018 to June 2019 and was carried out on the basis of SPIRIT Checklist for randomized studies. It was authorized via the Institutional Review Committee in Jinxiang Hospital Affiliated to Jining Medical College (JXHP0024578) and then was registered in research registry (researchregistry5832). Each patient received the written informed consent. Patients scheduled for a primary TKA were identified at the preoperative evaluation clinic, and in a private office, they were invited to meet with a research assistant who would confirm the eligibility, and interpret the research, and acquire the informed written consent. Inclusion criteria were 55 years or older, who possess the physical status I–III of American Society of Anesthesiologists, and the body mass index in the range of 18 to 30 kg/m2.2Seventy-two patients were divided into 2 groups randomly through utilizing the computer-generated forms and the drawing-coded sealed opaque envelopes. The anesthesiologist who conducted the block knew the treatment, but both the research assistant and the patient did not know about the grouping assignment. Study group (n = 36) received both ACB and LIA. Control group (n = 36) received ACB alone.2.3All patients were given the general anesthesia. The surgical procedures were performed by the senior surgeon. In the process of operation, pneumatic tourniquet was utilized. An incision was made in the center of the knee and then extended to the medial side of patella. All the ACB operations were conducted via an experienced anesthesiologist under the guidance of ultrasound. The patients were kept in the supine site, with the knee joint slightly bent and the leg rotated externally, and then 0.5% of the chlorhexidine spray skin was prepared. The ultrasound probe was utilized for the identification of the femoral artery and sartorius muscle. By passing through the sartorius into the adductor muscle duct and placing the needle appropriately until the needle tip could be seen by ultrasound. The needle aspiration was carried out to ensure that the femoral artery was not penetrated, and the experimental dose of 1 mL local anesthetic was injected. Ultrasound was used to observe whether the local anesthetic was diffused in internal adductor tube, so as to confirm the correct placement of the needle. Five to 10 milliliters 0.2% to 0.75% ropivacaine or 0.25% to 0.5% bupivacaine were then injected into adductor tube. The LIA was implemented utilizing 150 mg of ropivacaine, 30 mg of ketorolac, and adrenaline 200 μg as well as 10 mg of morphine, with 75 mL total volume, administered intraoperatively via surgeon.2.4Preoperative and postoperative clinical data were evaluated by an independent senior surgeon blinded to the patient's randomization. Primary outcome included postoperative pain score . Pain assessment was performed 12 hours after surgery, and pain was recorded at rest on the first and second days after surgery. The measures of secondary outcome included the knee range of motion, opioid consumption, the hospital stay length as well as the postoperative complications .2.5U test or the independent samples t test were used to analyze the inter group comparison. Chi-square detection was utilized to compare the categorical variables among the groups. Repeated data were analyzed by repeated measured analysis of variance. The P < .05 was regarded the significant in statistics.The calculations of sample size was conducted on the basis of our preliminary study. The results showed that ACB combined with LIA and ACB only reduced 24-hour postoperative opioid consumption from 14.9 ± 3.7 to 12.1 ± 4.8 mg. The number of 32 participants per group will provide 80% power to detect the equal difference in 24-hour opioid consumption at 2-sided alpha of 0.05. The definite 4 number of participants per group was 36 after compensation of data loss. All the analyses were implemented through utilizing SPSS for Windows Version 20.0. All the data are represented with proper characteristics as median, mean, percentage as well as standard deviation. Mann–Whitney 3The results are summarized in Table 4 The adductor canal consists of the medial femoral cutaneous nerve, medial femoral nerve, the posterior articular branches of obturator nerve, and sometimes the anterior branch from obturator nerve. Previous studies have reported that ACB showed similar pain relief and superior strength of musculi quadriceps femoris in comparison with femoral nerve block, and could thereby decrease the risk of falls during the postoperative rehabilitation process.,18 However, isolated ACB cannot provide complete analgesia to the posterior knee and LIA has a short-term action leading to less than satisfactory pain relief. Our research compares the efficacy of ACB combined with LIA and ACB alone in the treatment of postoperative pain after TKA. The sample size of our study is relatively small, and results may be underpowered to evaluate the efficacy of ACB along with LIA. High quality of randomized controlled trials with large sample size is required to convince our results.As the population ages, knee osteoarthritis has become more and more common. TKA has been widely performed for patients aged 60 years or older and it has become a serious public health issue. Meanwhile, approximately half of the patients undergoing TKA suffer from moderate to severe postoperative pain and effective pain control is regarded as a key to obtaining early ambulation and rehabilitative. Currently, there is still no reliable evidence or extensively accepted guideline for the best postoperative analgesia. Expert consensus has recommended the application of multimodal analgesia for reducing pain and opioid consumption after lower extremity surgery.5The study will provide more evidence on the combination use of ACB and LIA in the treatment of pain after the TKA.Limei Fan planned the study design and reviewed the study protocol. Qingchun Zhang has written the protocol and will recruit participants and collect data. All of them have read, commented on, and contributed to the submitted manuscript.Writing – original draft: Qingchun Zhang.