Most cases of low back pain (LBP) are regarded as non-specific and current studies indicate that for many this is a chronic recurrent condition, in which people experience episodes of pain with symptom-free periods in between. It is likely that acute exposure to some factors triggers the reappearance of new episodes in recurrent LBP regardless of the causality of the underlying condition (i.e. risk factors). Additionally, it has been shown that LBP patients present with different trajectories and different trajectories possibly have different triggers. Hence, dividing patients into some clinically meaningful subgroups may offer new insights into triggers, effective preventive strategies and, therefore, prognosis. This study aims to identify self-reported triggers and trajectories of episodes of recurrent LBP and to examine the prognostic association between different triggers and LBP trajectories.This is a longitudinal, multicentre, Australia-wide observational study of patients with recurrent non-specific LBP. Two hundred adults with at least a one-year history of LBP will be recruited from primary care clinics or private practices and followed for a year. Each will receive an SMS every fortnight  enquiring the occurrence of a new episode of pain in the past 2 weeks and its intensity. Upon report of a new episode, a telephone interview will be performed to appraise exposure to self-nominated triggers in a period of 24 h preceding the pain. Trajectories will be identified by latent class analysis at the end of the follow-up based on the pain intensity, frequency, and length of episodes. Triggers will be categorised into physical and psychosocial groups. Generalised linear mixed models with logit links will be used to explore pain triggers associated with pain trajectories.The completion of this study will provide insight into the patients’ self-reported triggers of LBP and also their possible prognostic association with different trajectories. Some newly-identified and pre-identified triggers are likely to be found and reported. Low-back pain (LBP) is among the most common causes of disability globally with a point prevalence of about 10–30% of the world population, with pain ranging from mild to severe –6. In thThe economic burden of chronic LBP such as inpatient or outpatient physical therapy, pharmacy, and work absenteeism is considerable and increasing, and seems to be comparable to the cost of other chronic conditions like heart disease or diabetes . There aIt is shown that the natural history of non-specific LBP does not follow precisely an acute, subacute or chronic pattern as described by Nachemson and Bigos back in 1984 . Today, LBP, in fact, could be compared to other chronic recurrent diseases such as asthma or migraine where it is believed that the ‘disease’ needs to be established first (i.e. the onset of the very first symptoms where one was disease-free/symptom-free previously), followed by episodes of exacerbations later during the course of the disease. Likewise, some people have the ‘disease’ of LBP with many ensuing back pain episodes (exacerbations) throughout their lives . Thus, iIn 2002, de Vet et al. highlighted the necessity for a clear definition of an episode and non-episode in order to bring unanimity into LBP research and make the interpretation of research findings more tangible . Since tAlmost all LBP studies confirmed a recurrent episodic or persistent pattern Various subgroups have been identified although based on different methods of classification –34.It was shown that there is a stable pattern across the course of LBP in individuals, and it is very unlikely for someone with severe or long-lasting LBP to become completely pain-free over time and vice versa , 35.With the Acknowledgement of LBP as an episodic, recurrent disorder, studying its course by just measuring, observing, and reporting on a few episodes or a few points in time at long intervals will not likely reflect the actual long-term course of LBP since data are missed between those measurements. In other words, those discontinuous measurements will not adequately describe the pain profile over time. In this respect, some studies have investigated LBP trajectories and the following points were identified as their major findings:However, unless the pain trajectories are properly recorded, it would not be possible to investigate if different trajectories have different prognoses, especially following treatment. Additionally, possible associated triggers can be studied and identified when investigating the trajectories of LBP. This potentially allows the specification of those triggers that exacerbate new episodes of pain and possibly cause different types of trajectories. Also, the knowledge of triggers of episodes of LBP could contribute to the effective prevention and self-management opportunity rather than attempting to ‘cure’ the condition.Steffens et al., in 2014, sought clinicians’ view on short- and long-term triggering factors of a new episode of LBP and found biomechanical factors as the main contributing causes for both. They, however, have only taken the physiotherapists’ point of view into consideration, not those of the patients’ themselves .In 2015, Steffens et al. conducted a case-crossover study, which looked at exposure to some pre-determined factors that they thought might act as triggers of acute episodes of LBP. They reviewed 999 patients who sought care in a primary care setting. Factors that were considered to contribute to the reoccurrence of a new episode were physical factors such as lifting heavy loads, awkward posture, physical activity, and psychosocial factors like alcohol intake and distraction during activity and fatigue. Exposure was measured 2 h, 24–26 h, and 48–50 h prior to the onset of back pain. All physical triggers were significantly associated with an elevated risk of an acute episode of LBP. Fatigue and distraction among psychosocial triggers were also associated with an increased risk of pain. Nevertheless, in this study, the authors only investigated one acute episode of LBP . A seconAnother study in 2016 compared patients’ and physiotherapists’ views on triggers for LBP. In this study, even though the category of biomechanical factors was identified as the main trigger by both patients and clinicians, there were some dissimilarities in its subcategory. No new factor was identified. Nonetheless, it seems that patients’ views were their general understanding and not episode-specific .Persuasively, it is likely that the outcome will be more plausible and trustworthy in a study where chronic recurrent LBP sufferers are followed for a more extended period, and triggers are identified for every single episode, since the prognostic association between triggers and trajectories may be recognised. Our literature search failed to reveal any study in which the aforementioned methodological strategies were implemented.This approach may enable clinical scientists to better understand the course of LBP and its relation to triggers. Also, frequent measurements allow researchers to take the number of episodes and their duration into account to accurately define episodes and non-episodes; something that is still lacking in the literature. Another advantage of repeated measurements is to potentially classify patients into appropriate clinical subgroups based on intensity, frequency, and duration of episodes that may suggest a new approach towards triggering factors, prevention, and prognosis.The primary aim of the study is to report the triggers of recurring episodes of LBP. The secondary aim is to examine the prognostic association between different triggers and LBP trajectories.To identify participants’ beliefs on the trigger(s) of their episodes of recurring LBPTo identify self-reported trajectories of recurring LBPTo identify clinicians’ views on triggers of LBPTo explore the agreement between patients’ and clinicians’ views on triggers of LBPThe objectives of this study are:This is a longitudinal, multicentre, Australia-wide observational study of patients with recurrent non-specific LBP. The study has been approved by the Human Research Ethics Committee at the Murdoch University, Perth, Western Australia (project number 2019/034).Eligible LBP sufferers who seek care from our participating clinicians are identified for inclusion and will be provided with an information letter and a consent form. Upon signing the consent form, the baseline questionnaire will be given to study participants to complete and be collected by clinicians. Consequently, participants will be enrolled in the SMS tracking system/software via their mobile phone numbers. Figure Data in this study will be gathered via a baseline questionnaire, frequent SMS-based questionnairs, telephone interview questionnaires, and clinicians' questionnaires.After enrolment in the study and registration into the automated SMS system/software, each patient will receive one SMS every 2 weeks to investigate the occurrence of any new episodes of LBP. If the patient reports a new recurrent episode of pain via SMS, they will be contacted via phone by a trained member of the research team, and a telephone interview will be scheduled and performed. If a patient forgets to answer the SMS, which may happen at the beginning, in particular, a member of the research team will contact them by phone and a new explanation of the study procedure/aims will be given. This approach is necessary to ensure high compliance.Patients with low back pain attending primary care clinics will be encouraged to participate in this study. We intend to recruit patients aged 18 years and older. There is no predilection about the per cent of males and females participating in this study. However, it is anticipated that the proportion will be approximately equal. The sample size is 200 (see below for details) and the study is planned to be conducted Australia wide.Patients aged 18 years and over who sought care for pain in the area between the 12th rib and buttock creaseHistory of non-specific recurrent low back pain in the past year without leg pain  in addition to a pain-free period in between)Mobile (smart) phone possession and ability to use its SMS functionAbility to understand, read and speak EnglishConsent, ability, and willingness to participate for the full duration of the study (52 weeks)The following criteria are considered for inclusion in the study:Persistent ongoing LBP, specific LBP such as radiculopathy, disc problems, spinal canal stenosis, fractures, and metastases.Secondary and tertiary care seekersHistory of spinal surgery or severe co-morbidities such as osteoarthritis, osteoporosis, uncontrolled diabetes (to be confirmed by our participating clinicians).LBP in special populations (e.g. Parkinson’s disease or pregnant women)The following criteria will exclude a patient from participating:Murdoch chiropractic alumni Murdoch University Chiropractic Clinic (MUCC)Australian Osteopathic AssociationChiropractic AustraliaAustralian Chiropractors AssociationThe Australian Chiropractic Research Network (ACORN)Supervisors at MUCCGeneral practitioners within a 10 km radius of Murdoch UniversityPhysiotherapy clinic at Curtin University of TechnologyDifferent clinicians and practices  will be approached to help recruit the study sample. Below is the list of potential organisations, practices, and clinicians, who will be contacted and asked for support:In this study, data are being collected via different questionnaires:Sociodemographic data will be collected when the patient consents to participate in the study. This consists of age, sex, height, weight, level of education, level of daily activity, an estimated number of episodes in the preceding year before the baseline, the  trajectory of their pain pattern in the past year , and depOnce enrolled, each participant receives one SMS fortnightly. Two short, simple questions will be asked in each SMS. Those questions enquire about the number of days with low back pain that had an effect on their daily activities (“troublesome”) in the past two weeks (0–14), and the severity of the pain at its worst (1–10) based on the NRS –48. PatiDuring the telephone interview, details regarding the recent episode of low back pain will be confirmed. These include the location and duration of the recent low back pain experience. An open-ended question will be asked relating to exposure to anything during the 24 h preceding the onset of this episode that the study participants believe could have triggered the current episode. Finally, prior exposure to some well-known and previously documented triggers will be investigated through a structured interview. These are fatigue, manual tasks, moderate and vigorous physical activity, distraction during a task. The open-ended question is asked first so as not to lead the participant.This short questionnaire contains some basic questions regarding clinician’s name, age, sex, contact details, types of practice/registration, and years in practice (this information is collected for description purposes and determination of diversity of the participating clinicians and study population). In addition, their views on triggers of non-specific low back pain will be solicited.n = 200 [n = 200–300 has been based on the optimal minimum sample size required for LCA, allowing for 20% contingency.As Latent Class Analysis (LCA) is not based around hypothesis testing, and there is no formal approach to calculate sample sizes. Critical factors that will affect sample size include prevalence, the sensitivity of items , and size of classes being fitted in the model. A broadly accurate guide indicated by other researchers uses a minimum of n = 200 –53. Thren = 200 has 80% power to detect an odds ratio of 1.35 in adjusted logistic models comparing pain triggers against pain trajectory outcomes  between four groups (obtained via LCA) over 26-time points, with alpha = 0.05 and beta = 0.2. (G*Power 3.1.7).A sample size of All descriptive summaries of patient characteristics, pain outcomes and pain triggers will include means and standard deviations or medians, interquartile ranges and ranges for continuous data and frequency distributions for categorical data. Data will be grouped according to demographic and other relevant patient factors including gender, age category, BMI category, and amount of physical activity  as well as pain pattern trajectories and triggers. All group comparisons will be performed using Chi-square tests for categorical data, and parametric one-way ANOVA or non-parametric Wilcoxon signed rank tests, depending on normality. Normality will be checked using graphical methods and Shapiro-Wilk tests. Data for patients lost to follow-up will be included up until the time of their abandonment.Latent Class Analysis (LCA) will be performed in order to identify pain pattern trajectories fortnightly over 12 months based on pain intensity, frequency, and length of episodes. Summaries of patient characteristics for each pain pattern trajectory will be described and compared between trajectories.Multinomial logistic regression or binary logistic regression using dummy variables will be used to examine patient characteristics as predictors of trajectory membership. Results will be summarised using odds ratios (ORs) and their 95% confidence intervals (CIs).Pain triggers will be identified from data obtained from open- and close-ended questions in the telephone interview questionnaires. All nominated triggers will be categorised into physical and psychosocial groups.Summaries of patient characteristics for trigger subgroups will be described and compared between trigger category subgroups such as age category, gender and physical activity categories.p < 0.15 in adjusted models will be entered into multivariable models and compared between trajectory groups in the final model. Results will be summarised using odds ratios (ORs) and their 95% confidence intervals (CIs).Generalised linear mixed models with logit links will be used to explore the associations of individual longitudinal pain triggers with pain pattern trajectories. Significant prognostic associations between individual pain triggers and pain pattern trajectories will be identified in adjusted models that will include relevant patients’ and clinicians’ characteristics as covariates. Individual triggers that are significant at p-values < 0.05 will be considered statistically significant. Sensitivity analysis will be performed, comparing patients with full follow-up data against patients with partial follow-up data.Missing values will be accounted for in the mixed model analyses which uses maximum likelihood estimation methods. However, we require a minimum number of 12 Consecutive followups (six months) for the LCA. Stata I/C version 16.0  will be used to perform data analyses. All analyses will be 2-tailed, and Upon completion of this project, trajectories of LBP in participants with recurrent LBP will be identified and reported. A series of newly identified and pre-identified triggers are likely to be found. Any prognostic association between triggers for the different trajectories will be described as will the association between the trajectories and a series of potential moderators on the assumption that they will differ between trajectory subgroups.Since no treatment has been found to be significantly superior or even better than placebo in the management of non-specific LBP thus far, it may be useful to consider LBP as a chronic condition with concomitant triggers. Therefore, an effective prevention plan and management opportunity might be achieved by dealing with the LBP triggers and trajectories as this may create the possibility of moving the responsibility of care to the patients using education and secondary prevention. It is predicated on the ability of patients being able to recognise the triggers  and thesIt is anticipated that outcome yielded from a study in which chronic recurrent LBP sufferers are followed for a longer period, and triggers are identified for every single episode, would offer more reliable preventive measures, management strategies and understanding of prognosis since the association between trajectories and triggers will be recognised.Patients’ preconceived ideas of triggersPatients’ opinions affected by their treating clinicians’ opinionsPredominantly chiropractic patients may be different from the broader population of back pain sufferersPotential sources of bias and error in this study are:Additionally, in this study, we will be comparing different individuals on the basis of their characteristics and also their physical and psychological triggers for their pain outcomes. This leaves some unmeasured factors that could potentially lead to bias.


Little is known about the chronicity of orofacial symptoms and how this influences the oral health-related quality of life in juvenile idiopathic arthritis (JIA). Therefore, our objectives were to study the long-term changes in self-reported orofacial symptoms, and to define the impact of orofacial symptoms on oral health-related quality of life in JIA.At baseline (T0), 157 consecutive JIA patients ≤20 years completed a patient pain questionnaire that incorporates domains related to the orofacial area. At the 2 year follow-up (T1), 113 patients completed the same questionnaire (response rate 72%) in addition to the Child Perception’s Questionnaire; a validated 31-item questionnaire addressing oral health-related quality of life.At T0, 53% (60/113) of patients reported the presence of orofacial pain, and 36% (41/113) of patients reported compromised orofacial function. At T1, 77% (46/60) of patients with pain at T0 reported persistent pain, and 66% (27/41) of patients with functional disability at T0 reported persistent disability. Patients with orofacial symptoms reported a significantly greater prevalence of negative impact of orofacial conditions on general quality of life and within the domains of emotional and social well-being compared to asymptomatic patients.Self-reported orofacial pain and functional disability were common findings in a cohort of JIA patients followed over 2 years. These symptoms seem to persist over time in most patients, and have a significant negative impact on oral health-related quality of life.The online version of this article (10.1186/s12969-018-0259-4) contains supplementary material, which is available to authorized users. Involvement of the temporomandibular joint (TMJ) is a common finding in patients with juvenile idiopathic arthritis (JIA) , 2. LongGenerally, there is a lack of knowledge of the long-term chronicity of orofacial symptoms in JIA. Although follow-up studies exist, the current knowledge of JIA-induced orofacial symptoms mainly originates from cross-sectional studies . Long-teThe purpose of this prospective observational cohort-study was: 1) To study the long-term changes in self-reported orofacial symptoms, 2) To study the impact of orofacial symptoms on oral health-related quality of life (OHRQOL). We hypothesized that the presence of orofacial symptoms would have a significant impact on the OHRQOL.This prospective observational study was conducted at the Section of Orthodontics, Department of Dentistry and Oral Health, Aarhus University, Denmark in the period between 2014 and 2017. Patients with JIA are referred to the Aarhus University orthodontic clinic from all pediatric rheumatology hospital centers in Western Denmark and are followed longitudinally regardless of presence or absence of TMJ arthritis. Therefore, the entire cohort seen at the Section of Orthodontics is a representation of the JIA population of Denmark. In 2014 and 2015, consecutive patients were invited to participate in the study. Participants completed a self-report questionnaire that assesses orofacial symptoms in JIA. In 2017, all patients from the baseline study were invited to participate in a two-year follow-up survey. Inclusion criteria were: 1) JIA-diagnosis according to the criteria of the International League of Associations for Rheumatology (ILAR) [At baseline (T0), consecutive patients were asked to complete a standardized patient questionnaire concerning symptoms within the last 2 weeks. The questionnaire was created in accordance with international consensus-based recommendations for orofacial assessment in JIA , and incAt follow-up T1), the patients were asked to complete the same questionnaire that they had completed at T0. In addition, they were asked to complete a validated 31-item questionnaire addressing OHRQOL (Child Perception’s Questionnaire) . The que, the patGraphical display revealed that numerical variables  were skewed and not normal distributed. All numerical and categorical variables were analyzed using Wilcoxon’s rank-sum tests for paired data variables and Mann-Whitney tests for unpaired data. Chi-square tests were used to assess changes in the prevalence of the specific characteristics of orofacial symptoms between T0 and T1. Agreement between the pain index composite variable (pain frequency x pain intensity) and patient global pain score was calculated using the Bland-Altman analysis . CorrelaAt T0, 157 eligible consecutive patients completed the questionnaire. All 157 patients were invited to participate in the two-year follow-up questionnaire survey. At T1 , 113 patients accepted the invitation and repeated the questionnaire (response rate 72%). Only patients who completed the questionnaires at both time points were included in the present study. The characteristics of the 113 study patients are presented in Table At T0, 55% of patients (62/113) reported the presence of orofacial symptoms and 45% of patients (51/113) were asymptomatic Fig. . The majAt T1, 77% (48/62) of patients reported “persistent symptoms” indicated by a report of symptoms at both time points (T0 and T1). Between T0 and T1, 27% (14/51) of patients developed new symptoms; 7% (1/14) reported functional disability only; 50% (7/14) reported pain only; and 43% (6/14) reported both pain and functional disability. Twenty-three percent (14/62) of patients with symptoms at T0 experienced a resolution of symptoms at T1 Fig. .n = 46) reported significantly higher pain frequencies than patients with newly developed pain between T0 and T1 (n = 13)  Fig. .Fig. 2a n = 60)  Fig. . A non-sn = 46) was reported by patients with persistent pain when compared to the median pain intensity of 16 mm  reported by patients with pain at T1 only  and patient global pain score was n = 60) was 43.5   when compared to a median 16 (IQR = 12–45) pain index reported by patients with pain at T1 only (n = 13). No significant changes in pain index values were observed between T0 and T1 in patients with persistent pain reports  Fig. . At T1, rts Fig. .Figure n = 41)  when compared to a median of 46 mm  in patients reporting functional disability at T1 only  Fig. . Ninety-41) Fig. . At T1, nly Fig. . The nonThe characteristics of orofacial symptoms reported at T0 and T1 are displayed in Fig. r = 0.32 was found between the pain index variable and global rating of self-reported perception of own oral health in patients with symptoms at T1, indicating a limited association between the severity of orofacial pain and the self-reported rating of own orofacial health.The global rating of self-reported perception of own oral health was significantly reduced in symptomatic as compared to asymptomatic patients at T1 Fig. . A subgrr = 0.54 was found between pain index values and the self-reported impact of orofacial condition on general quality of life in patients with symptoms at T1.The impact of orofacial conditions on general quality of life was significantly higher in patients reporting symptoms as compared to asymptomatic patients at T1 Fig. . A subgrThe impact of items related to emotional and social well-being among patients with and without TMJ-arthritis symptoms are presented in the online Additional file To our knowledge, this is the most comprehensive longitudinal study examining orofacial symptoms in JIA. The objective of this study was to study the long-term changes in self-reported orofacial symptoms and to study the impact of orofacial symptoms on OHRQOL. The findings of this study demonstrate: Orofacial symptoms are common findings in patients with JIA, and they tend to persist with time. Furthermore, the intensity, frequency and the characteristics of orofacial symptoms do not change significantly over time. The TMJ and masseter regions are the most frequent orofacial areas affected, however, multiregional orofacial pain was seen in a substantial number of patients with persistent symptoms. Orofacial pain is associated with functional disability in the majority of patients, and it is rare to see functional disability in the absence of orofacial pain. We found that the pain index composite variable (pain frequency x pain intensity) is an acceptable measure of patient global pain perception. Patients with orofacial symptoms reported a significantly higher negative impact of orofacial conditions on general quality of life compared to asymptomatic patients. Finally, patients with orofacial symptoms reported a significant negative impact on emotional and social well-being.This study found a high prevalence (55%) of JIA patients with orofacial pain and dysfunction. This is in contrast to a previous 5-year follow-up study by Twilt et al., who reported a smaller prevalence of orofacial pain 13%) and limited mandibular function (10%) % and lim. In agrer = 0.78 reveals that this may be a useful variable to address the fluctuation of orofacial pain in JIA. Interestingly, the reported T0 and T1 median pain index scores were surprisingly small considering the range 0–400 of the pain index outcome measure.The nature of the questionnaire used in this study allowed for a comprehensive analysis of changes in orofacial pain characteristics in JIA over time. In the group experiencing pain at both T0 and T1, we did not observe a specific pattern for changes in pain frequency or pain intensity over time. The current literature lacks information about orofacial pain frequency in JIA . This stIn the present study, patients reporting persistent T1 pain reported more widespread pain distribution as well as higher prevalence of multiregional pain compared to those reporting pain at T0 only. Notably, the locations of the affected pain regions and the characteristics of orofacial symptoms did not significantly change over time in patients with persistent orofacial symptoms.r = 0.54) between the pain index variable and the impact of an orofacial condition on general quality of life demonstrates that a high level of orofacial pain may not negatively impact general quality of life and vice versa.In this study, the presence of orofacial pain and/or functional disability significantly impacted general health related quality of life. This is in agreement with a previous study by Leksell et al. and Frid et al. , 15 but Patients with persistent orofacial symptoms experienced a greater impact on their general quality of life compared to patients with symptoms at T1 only. Although we do not have any information about pain related symptoms between those two observation points, this suggests that long-term symptoms impact general quality of life to a greater degree than short-term orofacial symptoms. Moreover, we also observed that patients who only had symptoms at T0 reported a significantly greater impact of orofacial conditions on general quality of life at T1 when compared to asymptomatic patients. This is an interesting finding, and may indicate that previous orofacial symptoms can impact general quality of life even after symptoms have resolved. However, the present study does not allow us to make firm conclusions in this regard. Future work with a larger patient cohort studied at more frequent time intervals could help to clarify some of these findings.In the present study, we used a validated questionnaire to assess domains related to emotional and social well-being . This isOur cohort consisted of consecutively enrolled JIA patients, from the entire JIA population in Denmark, thus decreasing the risk for selection bias at T0. Although the background cohort reflects the JIA population in Denmark, it should be noted that there were no patients with enthesitis-related arthritis and undifferentiated arthritis completing the questionnaires at both time-points in the present study. Furthermore, standardized questionnaires were used assessing orofacial symptoms and OHRQOL, thus minimizing the risk of information bias. There were however some limitations to this study. The current data does not contain information about presence/absence of TMJ inflammation at the time the questionnaires were completed; this would have been important information to collect. However, this is likely of minor significance since previous studies have revealed that the presence of orofacial pain is a weak predictor of TMJ arthritis . When inIn addition, the degree of fluctuation of orofacial symptoms during the 25-month observation period is unknown, since we only examined two time-points (T0 and T1). Therefore, the term “persistent symptoms” in patients with reports of orofacial symptoms at both time points is somewhat vague and does not accurately characterize the degree of fluctuation or persistence of symptoms between these time points.Self-reported orofacial pain and functional disability were common findings in a cohort of JIA patients followed over 2 years. These symptoms seem to persist over time in most patients, and significantly reduce OHRQOL. Based on the findings of this study, we strongly recommend incorporating a standardized orofacial examination into the assessment of children diagnosed with JIA. A sudden reduction in TMJ function and/or orofacial pain should prompt increase attention and appropriate referral of the patient for further examination, and if necessary, initiation of treatment.Additional file 1:Prevalence of items impacting the OHRQOL among patients with and without TMJ-arthritis symptoms. (DOCX 26 kb)


At baseline and four weeks, they were evaluated for the manual muscle test (MMT), the range of motion (ROM), pain visual analogue scale (VAS) scores, Shoulder Pain and Disability Index (SPADI) scores and Neck Disability Index (NDI) scores during the abduction, adduction, flexion, extension, external rotation and internal rotation of the shoulder joint. Differences in changes in pain VAS scores, NDI scores and SPADI scores at four weeks from baseline between the two groups reached statistical significance . US-guided MTrP injection is a more useful modality as compared with a blind injection in patients with MPS.We compared the feasibility of ultrasound (US)-guided myofascial trigger point (MTrP) injection with that of a blind injection technique following the use of shear wave elastography (SWE) for the measurement of stiffness at the MTrPs in patients with trapezius myofascial pain syndrome (MPS). A total of 41 patients ( Myofascial pain syndrome (MPS) is referred to as regional pain that arises from hyperirritable spots located within taut bands of the skeletal muscle, termed as myofascial trigger points (MTrPs). Its common etiologic factors include direct or indirect trauma, spine pathology, exposure to cumulative and repetitive strain, postural dysfunction and physical de-conditioning. Current treatment strategies for MPS are the elimination of underlying etiologic factors. Unless appropriately treated, such etiologic factors would reactivate MTrPs and then cause a persistent presence of MPS ,2,3,4.According to Simons, MTrPs are a commonly overlooked source of muskuloskeletal disorders although they commonly cause pain in patients with MPS. They are identified at an estimated prevalence of 30–93% in patients complaining of musculoskeletal pain. Indeed, there is great variability in the overall prevalence of active MTrPs, estimated at 46.1 ± 27.4% ,6,7. PreMTrPs are often present in the upper trapezius muscle, which accounts for approximately 85% of patients with MPS presenting with pain . They caWith technological advancements in imaging modalities, such as ultrasound (US), magnetic resonance imaging (MRI) or positron emission tomography (PET), it has become possible to make an accurate identification of biomarkers with a predictive value ,14. ThusOver the past decade, new in vivo imaging modalities, such as magnetic resonance elastography and US elastography, have emerged as a quantitative method for measuring shear mechanical properties of the soft tissue , including the skeletal muscle, through external induction of the shear wave or with the use of radiation force of US. Since then, its usefulness has been extended for a variety of tissues, such as liver, breast, biceps, trapezius, and rectus femoris muscle ,17. ConsGiven the above background, we conducted this preliminary pilot study to compare the feasibility of US-guided MTrP injection with that of a blind injection technique following the use of shear wave elastography (SWE) for the assessment of stiffness at the MTrPs in patients with MPS.n = 41) were diagnosed with MPS at the department of rehabilitation of our medical institution and then evaluated in the current study.Between 1 April and 31 May 2019, a total of 41 patients ((1)The patients aged between 40 and 49 years(2)The patients with active MTrPs presenting with spontaneous pain and tender nodules(3)The patients with a more than 1-month history of a palpable tender nodule in the upper trapezius .Inclusion criteria for the current study are as follows:(1)The patients presenting with symptoms that are similar to the MPS  .(2)The patients with serious underlying diseases that may cause tissue degeneration (3)The patients with cerebrovascular disorders that may cause spasticity in the morbid muscle (4)The patients with central nervous system injuries (5)The patients who were currently taking muscle relaxants or physical therapy(6)The patients who received a dry needling(7)The patients who are deemed to be ineligible for study participation according to our judgment .Exclusion criteria for the current study are as follows:n = 41) in the current study, it was approved by the Institutional Review Board (IRB) of our medical institution . The patients submitted a written informed consent. All procedures performed in this study were in accordance with the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards.We, therefore, enrolled a total of 41 patients  based on the Medical Research Council (MRC) grading system, the range of motion (ROM), pain VAS scores, the Shoulder Pain and Disability Index (SPADI) scores and the Neck Disability Index (NDI) scores during the abduction, adduction, flexion, extension, external rotation and internal rotation of the shoulder joint, the daily use of analgesics and the number of palpable tender nodules. Then, they were also evaluated for the measurement of stiffness at the MTrPs on SWE using the Aplio 400  .n = 21, US-guided injection combined with SWE) and the control group . In both groups, an SWE was performed in transverse imaging planes prior to injections, the tender point was located at the site where there was an increase in the stiffness at the MTrPs on SWE and tenderness was palpated on physical examination by a physical medicine and rehabilitation physician. Thus, the degree of stiffness at the MTrP was confirmed as the increased shear wave speed (SWS) within the region of interest (ROI) in patients with MPS. The size of the ROI on SWE was set at 1.4 cm × 1.4 cm. In addition, the degree of stiffness at the MTrPs on SWE was measured within a range of 0-200 kPA  MMT: An indicator of the muscle strength, the MRC grading system uses a 5-point scale: 0 = “Paralysis”, 1 = “Sole presence of a trace or flicker of the muscle contraction”, 2 = “The possibility of muscle movement with elimination of the gravity”, 3 = “The possibility of muscle movement against the gravity”, 4 = “Decreased muscle strength with the possibility of muscle movement against resistance”, and 5 = “Normal strength” .(2) ROM: The ROM is defined as the amount of motion that is available at a joint. It was measured, as previously described by Norkin and White, for which the anatomical position served as the starting position except for rotations in the transverse plane .(3) VAS: The VAS is composed of a straight line with the endpoints indicating extreme limits . For the assessment of pain, the patients were asked to mark their pain level on the line between the two endpoints. Accordingly, their pain level was defined as the distance extending from the point indicating ‘no pain at all’ and the mark .(4) SPADI: The patients responded to a self-administered questionnaire study based on the SPADI. The SPADI was developed to measure the shoulder pain and disability in an outpatient setting. It includes 13 items, 5 and 8 of which evaluate pain and disability, respectively. It was tested and then validated in a mixed group of male patients with shoulder pain presenting to ambulatory care. Then, it has been used in a primary care setting and a surgical setting where patients with rotator cuff disease, osteoarthritis rheumatoid arthritis, adhesive capsulitis, joint replacement surgery or shoulder symptoms are included . In the (5) NDI: A 10-item questionnaire measuring patients’ self-reported neck pain-related disability, the NDI has been shown to have a high “test-retest” reliability. As compared with other types of pain and disability measures, it has been found to be more valid. It comprises questions about activities of daily living, such as personal care, lifting, reading, work, driving, sleeping, recreational activities, pain intensity, concentration, and headache, each of which is measured based on a 5-point scale (0 = “No disability” and 5 = “Disability”). We used the Korean version of the NDI .t-test. A p-value of <0.05 was considered statistically significant.All data were expressed as mean ± SD (SD: standard deviation). Statistical analysis was done using the SPSS ver. 24.0 for windows . For efficacy assessment, efficacy outcome measures were analyzed using the Student’s n = 41) with MPS were enrolled in the current study. They consist of 18 men and 23 women, whose mean age was 44.27 ± 2.22 years old. As shown in n = 21) or the control group (n = 20). Their baseline characteristics are represented in A total of 41 patients . These results indicate that the degree of efficacy was significantly higher in the trial group as compared with the control group (p < 0.05).As shown in Although unclear, pathophysiologic mechanisms underlying the formation of MTrPs in patients with MPS are explained by a cascade of inflammatory events. In more detail, levels of inflammatory mediators are elevated and this causes capillary compression resulting in tissue ischemia. With the increased metabolic demands, the muscle and its adjacent soft tissue undergo structural alterations and damages. The resulting persistent presence of sarcomere contracture is liable to a long-standing presence of myofascial tenderness and local pain at the MTrPs ,28. It hInjections are frequently performed based on anatomical landmarks on palpation, thus termed as a blind technique . It remaThe accuracy of US-guided injections of treatment agents is of significance, as previously described in a cadaver study, diagnostic or therapeutic US-guided injections are an extremely effective modality at diverse locations. US-guided injections should, therefore, be considered to maximize injection accuracy and minimize potential complications . This isp = 0.003, 0.012 and 0.018, respectively). These results indicate that the degree of efficacy was significantly higher in the trial group as compared with the control group (p < 0.05). However, limitations of the current study are as follows: First, we failed to serve treatment arms, such as the US-guided injection with or without SWE, for which valid outcome measures should be considered. Second, we evaluated only a small series of patients at the secondary medical institution located in a rural area. We could not therefore completely rule out the possibility of selection bias.To summarize, our results showed that differences in changes in pain VAS scores, NDI scores and SPADI scores at four weeks from baseline between the two groups reached statistical significance (In conclusion, our results indicate that US-guided MTrP injection is a more useful modality as compared with a blind injection in patients with MPS.


Total knee arthroplasty (TKA) is one of the most common surgeries performed to relieve joint pain in patients with end‐stage osteoarthritis or rheumatic arthritis of the knee. However, TKA is followed by moderate to severe postoperative pain that affects postoperative rehabilitation, patient satisfaction, and overall outcomes. Historically, opioids have been widely used for perioperative pain management of TKA. However, opioids are associated with undesirable adverse effects, such as nausea, respiratory depression, and retention of urine, which limit their application in daily clinical practice. The aim of this review was to discuss the current postoperative pain management regimens for TKA. Our review of the literature demonstrated that multimodal analgesia is considered the optimal regimen for perioperative pain management of TKA and improves clinical outcomes and patient satisfaction, through a combination of several types of medications and delivery routes, including preemptive analgesia, neuraxial anesthesia, peripheral nerve blockade, patient‐controlled analgesia and local infiltration analgesia, and oral opioid/nonopioid medications. Multimodal analgesia provides superior pain relief, promotes recovery of the knee, and reduces opioid consumption and related adverse effects in patients undergoing TKA. Total knee arthroplasty (TKA) is commonly performed in patients with end‐stage osteoarthritis or rheumatic arthritis of the knee to relieve joint pain, increase mobility, and improve quality of life. However, TKA is followed by moderate to severe postoperative painIn 1996, the American Pain Society declared that pain was “the fifth vital sign”A review of the available literature was performed on 8 January 2019 through searching PubMed, Cochrane Library and EMBASE databases. The keyword terms “pain management,” “pain control,” and “total knee arthroplasty” were used for searching the literature. The titles, abstracts, and full texts of published studies were screened. As a result, 67 studies were included in this review. This entire process is depicted in Fig. With exploration of the mechanisms underlying postoperative pain in TKA, it has been verified that both peripheral and central mechanisms are involved. Therefore, monotherapy alone is not enough to provide satisfactory postoperative pain relief after TKA. At present, multimodal analgesia is considered as the optimal method for perioperative pain management of TKA through targeting numerous pain pathways. Multimodal analgesia was first introduced by Wall in 1988, referring to a combination of several types of medications and delivery routes, including preemptive analgesia, neuraxial anesthesia, peripheral nerve blockade (PNB), patient‐controlled analgesia (PCA), local infiltration analgesia (LIA), and oral opioid and nonopioid medicationMultimodal analgesia includes preoperative, intraoperative, and postoperative analgesic regimens, aiming to maximize the analgesic efficacy through the combination of several analgesic regimens, while minimizing undesired adverse effects. Adequate preemptive analgesia could prevent pain nociceptors from entering a state of hyperalgesia, and make acute postoperative pain easier to control, ultimately reducing opioid consumption. Intraoperatively, LIA is performed by a surgeon near the conclusion of a procedure that directly prevents the generation and conduction of pain signals from incision. Several medicines are available for LIA during the surgery, which will be discussed in detail later. Postoperatively, multimodal analgesia includes pharmacologic agents, neuraxial anesthesia, PNB, and PCA, each of which will be described below. Compared with a monotherapy, multimodal analgesia provides superior postoperative pain relief to promote recovery of the knee, and reduce opioid consumption and related side effectsPreemptive analgesia is defined as an antinociceptive intervention that starts before a surgical procedure. It is more effective than the same intervention when started after surgeryet al. (2018)et al.Cyclooxygenase‐2 (COX‐2) inhibitors, such as parecoxib sodium and celecoxib, administered 30–60 min before surgery significantly decrease postoperative pain and morphine consumption without increasing the incidence of other postoperative complicationsOpioids have long been used for the treatment of knee arthritis and perioperative pain management of patients undergoing primary TKA and revision knee arthroplasty. As analgesics, opioids inhibit the conduction of pain signals through activation of opioid receptors through several delivery methods, such as oral, intravenous, intramuscular, subcutaneous, and transdermal. Although opioids are effective in pain management after TKA, there are some adverse effects associated with them, such as itchiness, nausea, somnolence, respiratory depression, retention of urine, and constipation. In addition, long‐term use of opioid medications may lead to tolerance and dependence that require increasing doses to achieve the same effects. Therefore, it is practical to apply other analgesic regimens to reduce the amount of opioid consumption.et al. (2017) suggested that approximately one‐third of TKA patients used opioids within 3 months prior to surgeryet al.Bedard et al. 20 suggesteTraditional nonsteroidal anti‐inflammatory drugs (NSAID) and COX‐2 inhibitors provide perioperative analgesia through inhibition of COX‐2 and prostaglandins. NSAID also inhibit the activity of COX‐1 that is associated with gastrointestinal effects. In addition, NSAID increase the risk of perioperative blood loss. Fortunately, COX‐2 inhibitors have a favorable adverse effect profile with reduced gastrointestinal effects and risk of blood losset al.et al.A meta‐analysis conducted by Lin Local infiltration analgesia (LIA) has received increasing interest in recent years because of the associated low risk, simple performance, low complication rates, and reduced local anesthetic systemic toxicity. LIA is performed by a surgeon intraoperatively without specialist equipment, commonly near the conclusion of a procedure. Local anesthetic combined with opioids, antibiotics, NSAID or epinephrine (cocktail) are injected into periarticular regions, including the posterior capsule, collateral ligaments, capsular incision, the quadriceps tendon, and subcutaneous tissues, which directly prevents the generation and conduction of pain signals from incision. Recently, LIA has become an alternative analgesic regimen to femoral nerve block (FNB) without resulting in impairment of quadriceps muscle strength. Nevertheless, there is still no consensus on the optimal composition and infiltration technique of LIA. Common LIA cocktails are listed in Table et al.et al.et al.et al.Among the patients undergoing TKA, those patients who received intraoperative LIA achieved improvement in pain scores and comparable satisfaction levels, with reduced total narcotic consumption in the early postoperative period compared to those with placebo infiltrationet al. (2018)vs 84.9 mg, P = 0.0048), and time to first opioid rescue without side effectsvs 3.87, P = 0.02) and higher range of motion  in the first 24 h, the patients receiving LIA with LB were significantly more likely to perform a straight leg raise 12 h postoperatively  and scored better in the physical function component of the Short Form‐12  3 months postoperativelyLiposomal bupivacaine (LB) is used as a component of the LIA cocktail to prolong the effect of LIA, for LB can last up to 72 hours. Several studies have assessed the efficacy of LIA with LB in patients undergoing TKA, but the results are controversialDifferent results of efficacy of LIA compared with other analgesia protocols are obtained from different studies, which reach no consensus in optimal composition and infiltration techniques of LIA. A previous study suggested that it was intraoperative periarticular instead of intraarticular infiltration that was effective in pain control in the early postoperative period after TKAvs 0.92%, P = 0.0003), blood transfusions , length of surgery , and length of hospital stay et al.P < 0.001), postoperative room time , and postoperative hospital stay , and had more surgical site infections  and blood transfusions  compared to those with spinal anesthesia. However, there were no differences in operative duration and other adverse events. In addition, Mahan et al.vs 33.6 ± 14.4 h, P = 0.002), fewer episodes of straight catheterization  compared to bupivacaine, and exhibited no differences in postoperative pain or morphine consumption.Anesthesia choice is an issue for better perioperative outcomes after TKA. In addition, pain management after TKA is affected by the type of anesthesia used for the surgery. Both general and spinal anesthesia are appropriate for TKA. Because general anesthesia is associated with reduced perioperative tissue oxygen tension as well as postoperative nausea, vomiting, and delirium, it is initially considered the gold standard for hip and knee arthroplastyet al. (2018) of seven RCT, with 251 patients undergoing TKA, concluded that LIA was as effective as epidural anesthesia for pain controlFormerly, epidural analgesia was used as a regular postoperative analgesic regimen for patients after TKA, consisting of a local anesthetic agent and an opioid. Compared with parenteral opioids, epidural analgesia provides better postoperative analgesia with less nausea, vomiting, and pruritusPeripheral nerve blockade is usually used to relieve postoperative pain of TKA. PNB could significantly reduce consumption of opioid and opioid‐related adverse effects. It also promotes early mobilization and reduces the length of hospital stay. The knee joint is innervated by several nerves, including the femoral nerve, the sciatic nerve, the obturator nerve, the saphenous nerve, and the lateral femoral cutaneous nerve. Among these, the femoral nerve is an important one with respect to analgesic effects after TKA. Consequently, FNB is one of the most commonly used PNB, and has been widely accepted as the gold standard for pain relief after TKA. FNB not only provides excellent pain management after TKA but also reduces opioid consumption, hospital stay, and incidence of nausea and vomitingThe adductor canal is located in the middle one‐third of the thigh and runs from the apex of the femoral triangle proximally to the adductor hiatus distallyPatient‐controlled analgesia is widely used for pain management in patients after TKA to provide simple, fast, and adequate pain relief without a specialized anesthesiologist postoperatively. The device is programmed according to the analgesic used, the physical characteristics, and the baseline pain of the patients. A small amount of analgesic could be delivered by the patients pressing the button when they most need it. Usually, opioids are used in PCA, such as oxycodone, morphine, fentanyl, and hydromorphoneWith the aging of the population, there will be an increasing number of elderly patients receiving TKA. Perioperative pain management in patients undergoing TKA is very important to improve rehabilitation, patient satisfaction, and overall outcomes. Furthermore, when surgeons make a plan for perioperative pain management after TKA, they must consider each patient individually. At present, multimodal analgesia is the optimal analgesic regimen for TKA. Multimodal analgesia could improve perioperative pain control and patient satisfaction through the combination of several analgesic regimens, while reducing opioid consumption and opioid‐related adverse effects. However, the optimal protocol of multimodal analgesia needs to be further investigated in the future.


Introduction: Referred to as the “fifth vital sign”, pain is unique in that it cannot be obtained accurately by objective measurements. Instead, providers rely on patient-reported scales, such as the numerical rating scale (NRS), to determine a patient’s pain level. Research has shown that patients report different pain scores to nurses and physicians in the clinic setting. It is unknown if this also occurs in the acute postoperative period. We hypothesized that patients report similar pain scores to the nursing staff and physician postoperatively. The primary aim of this study was to examine the degree of agreement between these patient-reported pain scores.Methods: A prospective study was conducted on 90 postoperative patients. During rounds, the surgeon collected a patient-reported pain score using the 11-point verbal NRS. Following rounds, the nursing staff obtained a pain score using the same scale. The patient was blinded to the study.Results: The median score reported to both the surgeon and nurses was 3 (range: 0-10), with a median difference of 0 (range: -2.5 to 7). Fifty-four percent of patients reported the same score to both the surgeon and the nurse and 88% of patients reported scores within a 1-point difference. This corresponded to an interclass correlation coefficient of 0.90, indicating very good agreement. The degree of agreement in pain scores reported to surgeons and nurses was consistent according to sex and age.Conclusion: The results of the study demonstrate a high degree of agreement between the pain scores reported by the patients to both the nursing staff and the surgeon postoperatively, with 88% of the scores at most being 1-point different. Effective pain control has long been a priority in patient care. Often referred to as the “fifth vital sign”, pain is unique from the more traditional vital signs in that it cannot be easily obtained accurately by objective measurements. Instead, medical providers rely on several patient-reported subjective pain scales, such as the visual analog scale (VAS) or numerical rating scale (NRS) to determine a patient’s pain level -4. HowevThere is additional concern with relying solely on these subjective measurements for pain as patient care is often directed from these self-reported scores. Previous research has demonstrated that patients report different pain scores to the nursing staff and physician during the same clinic visit -8. It isThe primary aim of this study, therefore, was to evaluate the degree of agreement between the patient-reported pain score provided to the surgeon as compared to the score provided to the nursing staff in a blinded fashion. Additionally, the secondary aim was to assess the association between the reported pain score and whether the patient felt that their pain was adequately controlled. We hypothesized that patients would report similar pain scores to the nursing staff and physicians postoperatively.Following the Institutional Review Board (IRB) approval, we conducted a prospective single-blinded study to compare patient-reported pain scores provided to the physician as compared to the nursing staff. The data was collected on 90 postoperative patients during inpatient surgical rounds at the Mayo Clinic in Florida from June to September 2018. The baseline characteristics that were collected included age, gender, and pre-operative NRS pain score. The pre-operative pain score was collected in the preoperative holding bay by the perioperative nursing staff on the day of surgery. Postoperative measurements recorded included pain scores reported to the surgeon, pain scores reported to the nurse, the time between physician-assessed and nurse-assessed pain scores, and whether the patients’ pain was adequately controlled (as reported by the patient to the surgeon). The primary outcome measure was the difference between pain scores reported to the surgeon and nurse . Pain scores were collected on average on postoperative day 1 (range: 1-5 days). During rounds, the physician collected the data by asking the patient to state their current pain level on an 11-point verbal NRS, with 0 equaling “no pain” and 10 equaling “the worst pain”. After the patient had given a rating for their pain level, the physician then asked if the patient considered the pain to be currently controlled (yes or no). The time that the patient responded to the physician was recorded. The nursing staff was not present during the physician collected data.Once the surgical team finished daily inpatient rounds, a researcher returned to the surgical floor and asked the nursing staff to enter the room and obtain a patient-reported pain score using the same 11-point verbal NRS scale. No member of the surgical team, including the researcher, were in the room or in sight of the patient during the nurse’s collection of data to eliminate bias. The nurse-collected scores were obtained within 60 minutes following the physician-collected data, and were prior to any pain-inciting events, such as physical therapy or movement from the bed to chair.The patients were blinded to the study until after the data was collected, after which they were informed of the study by the research team and consented to include their data in the analysis. No patients refused to consent. All patients included in the cohort were able to consent themselves and were free of a diagnosis of delirium or dementia. For patients undergoing multiple staged procedures, only the first operative orthopedic procedure and first recorded NRS pain scores for each patient were included in the analysis in order to satisfy the statistical assumption of independent measurements.The median patient age in the cohort was 66 years (range: 19 - 101 years) and 40 patients (44%) were male. The median pre-operative NRS pain score was 0 (range: 0 - 10), and 51 patients (57.3%) had a value equal to zero. The majority of patients underwent an elective operation such as a hip or knee replacement procedure . Additional procedures included a hemiarthroplasty or cannulated screws for a femoral neck fracture , soft tissue mass excisions , pelvic debridement procedures , and irrigation and debridement for infection .Statistical analysis continuous variables were summarized with the sample median and range, while categorical variables were summarized with number and percentage. Agreement in NRS pain scores as reported to the surgeon and nurses was assessed for the overall series as well as separately according to sex and age (<65 or ≥65 years). To estimate this degree of agreement in pain scores, we first estimated the proportion of patients for whom pain scores reported to the surgeon and nurses were equal or within one point of each other. Subsequently, the agreement between surgeon and nurse NRS pain scores was estimated using the intraclass correlation coefficient (ICC) along with a 95% confidence interval (CI); an ICC equal to 0 indicates no agreement and an ICC equal to 1 indicates perfect agreement.To evaluate the secondary aim of the study, NRS pain scores reported to the surgeon were compared according to whether the patients’ pain was controlled or not using a Wilcoxon rank-sum test. All statistical tests were two sided. P-values less than 0.05 were considered as statistically significant. Statistical analysis was performed using R Statistical Software .Postoperative pain scores reported to surgeons and nurses are summarized in Table Of the 90 patients, 75 84.3%) reported that their pain was adequately controlled (this information was not available for one patient). For the secondary aim of the study, we compared the NRS pain score for patients who reported that their pain was or was not adequately controlled. For the patients who reported to the surgeon that their pain was adequately controlled, NRS pain scores reported to the surgeon were significantly lower compared to the pain scores for patients who reported that their pain was not adequately controlled (P< 0.001), with a difference in median NRS pain scores of 5.5 points. It is worth noting, however, that there was some overlap in NRS pain scores for these two patient groups in the 5-7 range  for patients to become distracted with other activities while not allowing enough time for pain-inciting events, such as physical therapy, to influence the results.In conclusion, the results of this study indicate that there is very good agreement between physician and nursing-obtained verbal numerical rating pain scores, with 88% of the scores at most being 1-point different, demonstrating no clinically significant difference. Additionally, as expected, NRS pain scores were dramatically lower in patients who reported that their pain was adequately controlled in comparison to patients whose pain was uncontrolled. Interestingly, there was some overlap in the reported pain scores between the two groups in the 5-7 range of the NRS scale, suggesting that medical providers should further inquire about the patient’s perceived pain control in this range to avoid over or under-treatment of pain.


Background: There is limited evidence concerning the effect of intramuscular electrical stimulation (EIMS) on the neural mechanisms of pain and disability associated with chronic Myofascial Pain Syndrome (MPS).Objectives: To provide new insights into the EIMS long-term effect on pain and disability related to chronic MPS (primary outcomes). To assess if the neuroplasticity state at baseline could predict the long-term impact of EIMS on disability due to MPS we examined the relationship between the serum brain-derived-neurotrophic-factor (BDNF) and by motor evoked potential (MEP). Also, we evaluated if the EIMS could improve the descending pain modulatory system (DPMS) and the cortical excitability measured by transcranial magnetic stimulation (TMS) parameters.Methods: We included 24 right-handed female with chronic MPS, 19–65 years old. They were randomically allocated to receive ten sessions of EIMS, 2 Hz at the cervical paraspinal region or a sham intervention (n = 12).Results: A mixed model analysis of variance revealed that EIMS decreased daily pain scores by -73.02% [95% confidence interval (CI) = -95.28 to -52.30] and disability due to pain -43.19  at 3 months of follow up. The relative risk for using analgesics was 2.95  in the sham group. In the EIMS and sham, the change on the Numerical Pain Scale (NPS0-10) throughout CPM-task was -2.04 (0.79) vs. -0.94 (1.18), respectively, (P = 0.01). EIMS reduced the MEP -28.79 (-53.44 to -4.15), while improved DPMS and intracortical inhibition. The MEP amplitude before treatment  and a more significant change from pre- to post-treatment on serum BDNF)  were predictors to EIMS effect on pain and disability due to pain.Conclusion: These findings suggest that a bottom–up effect induced by the EIMS reduced the analgesic use, improved pain, and disability due to chronic MPS. This effect might be mediated by an enhancing of corticospinal inhibition as seen by an increase in IC and a decrease in MEP amplitude. Likewise, the MEP amplitude before treatment and the changes induced by the EIMS in the serum BDNF predicted it’s long-term clinical impact on pain and disability due MPS.ClinicalTrials.govThe trial is recorded in : NCT02381171. Myofascial pain syndrome (MPS) encompasses muscle and musculotendinous pain secondary to the development of myofascial trigger points (MTrPS). It is the principal source of pain in about 30% of individuals with musculoskeletal dysfunction, and its primary components are MTrPS, tender points, and taut bands. The trigger point induced central sensitization explains the referred pain and hyperalgesia phenomenon . CentralThe transcranial magnetic stimulation (TMS) measures have proven to be useful to assess cortical physiological processes . Previously, we found that hyperexcitability in the cortical-spinal pathway as measured by motor evoked potential (MEP) amplitude was positively correlated with the disengagement of the descending pain modulatory system (DPMS) . Also, iN-methyl-D-aspartate (NMDA) (These changes in excitatory and inhibitory transmitter systems are confluent with a reduction in the descending inhibitory pathways . As afore (NMDA) . Additioe (NMDA) . Notablye (NMDA) . HoweverThe EIMS is a technique of electroacupuncture used to modulate pain processing in a bottom–up fashion. Although the neuroplasticity processes involved in its effect is not yet well comprehended , it has We investigated the effect of 10 sessions of EIMS to test the primary hypothesis: To provide new insights into the EIMS long-term effect on pain and disability related to chronic MPS (primary outcomes). Also, we tested another secondary hypothesis: (i) if the neuroplasticity state at baseline could predict the long-term impact of EIMS on disability due to MPS we examined the relationship between the serum brain-derived-neurotrophic-factor (BDNF) and by MEP. (ii) If the EIMS could improve the DPMS assessed by the change in the score on Numerical Pain Scale (NPS0-10) at the Conditioned Pain Modulation test (CPM-task) induced by cold water (0–1°C). (iii) And if it changes the cortical excitability parameters indexed by TMS parameters . We hypothesize that the EIMS analgesia is related to changes at the pain pathways at cortical and infra-cortical levels and that TMS parameters and serum BDNF are reliable markers of neuroplasticity state.Figure 1.The methods and results are presented according to the CONSORT guidelines . The floThe Research Ethics Committee approved the protocol of this study at the Hospital de Clínicas de Porto Alegre (HCPA)  following the Declaration of Helsinki. Before participating in this randomized, double-blind, two-group parallel, clinical trial, all patients provided their oral and written informed consent.Twenty-four right-handed female patients, aged 19–65 years with a diagnosis of MPS in the upper body part were recruited. They should have clinical criteria to MPS . They should report some restrictions for the routine activities due to pain for at least 3 months as assessed using a questionnaire with six specific questions (yes/no). These questions were intended to evaluate interference with personal relationships, work, personal goals, pleasure with activities, and clear thinking . To be enrolled, subjects had to give an affirmative answer to one or more of the six questions mentioned above. Moreover, a second independent investigator with more than 10 years of experience to care for patients with chronic MPS confirmed the diagnosis after a standard clinical examination. They should describe the pain as dull, hollow or deep and aggravated during stress. The Neuropathic Pain Diagnostic Questionnaire (DN4) was employed to distinguish neuropathic pain from continuing nociception. To standardize the diagnosis of MPS concerning the severity, only patients with a neuropathic pain component were included  on DN4 .The exclusion criteria comprised the presence any other pain diagnosis, such as radiculopathy, rheumatoid arthritis, fibromyalgia; previous surgery on the affected areas; constant usage of anti-inflammatory steroids (because they could interfere in TMS measures). Also, patients with oncologic or neurologic disease history, hepatic or kidney insufficiency, and ischemic heart disease or those with criteria to contra-indicated TMS use according to the international guideline were excluded. If they had a history of alcohol or substance abuse during the previous 6 months were also excluded.SD = 1.2), for a error type I equal to 1% and an error type II equal to 20%, respectively. We included 24 patients (12 per groups) to account for possible dropouts.The sample size was estimated based on previous clinical trial . A samplWe used software to generate the sequence of randomization with a fixed block size of 6. Twenty-four patients were randomly allocated to receive treatment (EIMS or sham). Before the recruitment phase, opaque brown envelopes containing the protocol were prepared. The envelope contained a numerical code corresponding to the allocated treatment. Each envelope was opened in sequence according to the number that existed externally after the participant agrees to engage in the study. Only the physician responsible for administering the interventions was not blinded to treatment.To guarantee the blinding, during the whole timeline protocol, two investigators who not involved in the patient’s evaluations were responsible for handling the randomization code. Also, to reduce the potential to bias the EIMS was administered by the same physician (with more than 10 years of practice in acupuncture). Furthermore, the participants were requested to debate treatment details only with the physician who administered the EIMS sessions. Pain assessments, psychological tests and measures of cortical excitability by TMS was done by two trained examiners who were blinded to the interventions group.Figure 2) and semispinalis capitis (C2 and C3). The needles were inserted at the paraspinal region at 1.5 cm from the spinous process line . The accessory nerves were stimulated to record a motor response from the trapezius muscle  connected to an electroacupuncture device . The current was delivered to EIMS in the paraspinal region related to the nerve roots involved in the splenius capitis (C3 and C4) . While the stimulator was left in front of the participant for 20 min, to ensure that the flashing diode corresponding to the electrical stimulus was both audible and visible. All patients received ten sessions with 20-min of duration.The same electroacupuncture device , described above was used for the sham control condition. However, the output jack plug was broken to avoid no electrical current could move to the patient. We fixed the electrodes at the same spots where active stimulation would be applied. That is, at the paraspinal region at 1.5 cm from the spinous process line, at the border of the sternocleidomastoid muscle and to stimulate the accessory nerves we fixed the electrodes at the anterior border of the trapezius muscle (The primary outcomes comprise disability due to pain in the Brazilian Profile of Chronic Pain: Screen (B-PCP:S) and the pain reported on the VAS registered in a diary. Secondary outcomes were the analgesics doses used weekly during the treatment period, the change on Numerical Pain Scale (NPS0-10) during the conditioned pain modulation (CPM-task) and heat pain threshold (HPT). Also, we assessed the cortical excitability measures , and daily sleep quality. Below, we described the outcomes assessment in details.(a) Pain intensity was evaluated using a 10-cm VAS. The scores in VAS ranged from zero (no pain) to 10 (worst possible pain). We request to patients to report the pain score in the most part of the time in the last 24 h? So, to increase the compliance, an examiner checked the patients’ pain diary during the 12 weeks of follow-up.(b) To assess the multidimensional pain experience we used the Brazilian Profile of Chronic Pain: Screen (B-PCP:S) . The B-P®, tramadol or codeine) for pain relief, if necessary. They were authorized used 750 mg of acetaminophen up to four times per day (QID) and 200 mg of ibuprofen up to QID as rescue analgesics. If these drugs were not sufficient, patients could use Dorflex® . If they persisted with pain, It was allowed to use 60 mg of codeine up to QID or tramadol three times per day (TID). Patients recorded the rescue of analgesic used in a pain diary, which was checked during every intervention session and each visit of the follow-up. For analysis, we considered the total analgesic dose used throughout treatment.(c) Supplementary analgesia use: Patients could use additional analgesic drugs  The Quantitative Sensory Testing (QST) assessed the HPT. We used a thermode (30 × 30 mm) in a computer Peltier-based device using the method of limits. A temperature of 32°C was set with an increased at a 1°C/s rate, to a maximum of 52°C. The thermode was fixed to the skin on the ventral surface of the mid-forearm. The HPT was defined as the mean of three following measures of painful temperature. The thermode remained on the left ventral forearm; its position was slightly altered between trials to prevent either response suppression of the cutaneous heat nociceptors or sensitization .(e) To assess descending pain modulatory by a heterotopic noxious stimulus (CPM), we set the temperature to the point that each patient rating 6/10 pain on the NPS(0-10). The CPM test was performed 30 s following 1-min immersion of the non-dominant hand in cold water (zero to one degree Celsius). The CPM-task was the score in the NPS 0-10 induced by the QST during the cold-water immersion (QST + CPM) at the temperature produced by the QST that they were rating 6/10. CPM-task test was performed after we measured the parameters of cortical excitability. To control for individual variability, the proportion of difference from baseline was used was used for the analysis .(f) Daily sleep quality was measured by a 10-cm visual analog sleep quality scale (VASQS) which scores ranged from zero  to 10 . The following question was asked to patients to answer in their sleep diaries: “How well did you sleep last night compared with your habitual sleep?”(g) The assessment of the cortical excitability parameters, recordings via surface electromyography placed at the contralateral right first dorsal interosseous muscles using Ag/AgCl electrodes were used. Firstly, the Resting Motor Threshold (RMT) was established by obtaining five MEPs with the peak-to-peak amplitude of at least 50 μV out of ten successive trials. Afterward, we documented ten MEPs with an intensity of 130% of the individual RMT. Additionally, we determined the CSPs during muscle activity measured by a dynamometer at 20% of the maximal force. Ten CSPs were assessed using an intensity of 130% of the RMT. An inter-stimulus interval of 2 ms was used to evaluate the SICI. We set the conditioning (first) stimulus at 80% of the RMT, and we set the test stimulus at 100% of the individual MEP magnitude. We determined the ICF with an inter-stimulus interval of 12 ms. We measured the paired-pulse of TMS in a randomized arrangement for a total of 30 trials . Off-line analyzes included the collection of the amplitudes of all of the MEPs, SICI and ICF as well as the extension of the CSPs. The equivalent units for these parameters included MEP in μV, ICF and SICI in their ratio to the MEP, and ms for the CSP .g in plastic tubes for 10 min at 4°C and were stored at -80°C for hormone assay. An Enzyme-Linked Immunosorbent Assay (ELISA) using a ChemiKine BDNF Sandwich ELISA Kit, CYT306  was used to determine the serum BDNF. The lower detection limit of the kit is 7.8 pg/mL for BDNF.All psychological instruments used in this study had been validated for the Brazilian Portuguese . Two indT-Tests for independent samples and Chi-squared or Fisher’s exact tests were used to compare continuous and categorical variables between intervention groups, respectively. The analysis of the effect of the interventions on the outcomes  during CPM-task) was determined using a mixed ANOVA model. The independent variables were time, experimental group (EIMS or sham), the interaction between time and experimental group, and the subject identification as a within-subject factor. .Table 3). To assess if the neurophysiological state of the corticospinal pathway and the neuroplastic changes associated with the treatment, we analyze the effect of group in a mixed regression model (Table 4). The dependent variable was the cumulative mean B-PCP:S score from baseline to end follow up.To evaluate the mean difference in the cortical excitability measures  we calculate the percentage change at baseline to end treatment, which were compared using the Wilcoxon–Mann Whitney. The cortical excitability measures at the end of treatment we lost in one patient of EIMS group. Thus, to carry forward analysis using the intention-to-treat approach, we considered the effect observed in the worst case of the respective treatment group .Table 1. Twelve patients were assigned to the sham group, and 12 were allocated to the EIMS group. Twenty-three patients completed the study; one patient in the EIMS group withdrew due to needle phobia. The baseline characteristics were similar across the EIMS and sham groups  (Table 1). We did not observe any severe or moderate side effects from the interventions.Patients demographic and clinical features are shown in P < 0.001) than the sham group (Table 2), and there was no interaction between time and intervention group (P = 0.92) . Compared to the sham group, the EIMS group displayed a relative mean pain reduction of -73.02% (effect size of 0.55) at 12 weeks after the conclusion of the interventions (Table 2). Compared to baseline, the superior effect of EIMS was also evident: in the second week of treatment the EIMS group had a pain reduction of 55.31% compared to baseline.After treatment, the EIMS group had significantly lower pain scores in the VAS  (Table 2). There was effect of time and interaction between time and intervention group . The changes on B-PCP:S in follow-up was presented in Figure 4. This effect persisted until the 8th week following the end of the intervention, with an effect size of 0.8.The EIMS group had significantly higher improvement in the mean B-PCP:S score (P < 0.01).Analgesic use was reported in 69.4% during the treatment period in the sham group and 30.6% in the EIMS group. The relative risk for using analgesic during the 14 weeks (two treatment weeks and 12 weeks of follow-up) was 2.95 ; that is, the sham group used almost threefold additional analgesics. There was a significant decrease in the analgesic doses for patients receiving EIMS compared to those receiving sham (Table 2) and induced a 61.27% reduction in the pain scores on the NRS during the evoked pain by QST vs. QST + CPM . These findings suggest that the EIMS-intervention also induced an effect on the bottom up inhibitory mechanisms.The EIMS increased the HPT (P > 0.05), respectively. After ten sessions of treatment, the change on the NPS(0-10) during CPM-task in EIMS and sham was -2.04 (0.79) vs. -0.94 (1.18), respectively. The difference mean was – 1.25 (-2.07 to -0.18), (P = 0.01).The scores on numerical pain rating scale before treatment (QST vs. QST + CPM) in EIMS and sham group was -1.49 (1.99) vs. -1.77 (3.09) (Table 3) (P = 0.02) and increased the SICI by 37.41% (P = 0.005). However, the EIMS did not induce significant changes in ICF and CSP (Table 2).Compared to the group allocated to sham, the EIMS decreased the MEP by 28.79% (P = 0.004). However, the EIMS improved the VAS-QS by 12.75% in the previous night sleep quality compared with habitual sleep.There was no interaction between time and intervention group for the previous night sleep quality compared with the habitual sleep quality based on the VAS-QS scores (Table 4).One crucial issue is to identify markers associated with the long-term effect on pain and disability assessed by B-PCP:S. To address this critical matter, we run a mixed regression model in which we controlled the change on the B-PCP:S score from the end of treatment for both parameters, MEP at baseline and the change on serum BDNF from baseline to end treatment (P < 0.01) compared to EIMS when we compared the mean of percentage change from the baseline. Afterward, we ran a multivariate mixed regression model, which showed an interaction between treatment groups (EIMS or sham) and BDNF (P < 0.05) (Table 4). This result suggests that the increase in the BDNF is intervention dependent. Also, it indicates that the change in BDNF induced by EIMS may be a marker that predicts the long-term effect of treatment, as assessed by the B-PCP:S and the VAS 12 weeks after end treatment. Our findings showed that more substantial increase in serum BDNF induced by the EIMS and that higher excitability in the corticospinal pathway as measured by the MEP at baseline, both were correlated negatively with pain and disability at the end of follow-up. Also, it indicates that EIMS effect induced the more significant increase of serum BDNF.At the baseline, the serum BDNF in sham and EIMS groups was 27.11 (10.97) vs. 26.21 (6.83), respectively. While at end treatment the serum BDNF in the sham and EIMS groups was 25.05 (10.45) vs. 31.93 (10.74), respectively. Thus, to adjust to individual characteristics, we calculated the percentage of change from baseline to treatment end. The mean (SD) of the percentage of change in the sham and EIMS groups was -6.06 (19.53) vs. 28.74 (25.57), respectively. The Mann–Whitney Test showed that sham group had a significantly lower serum BDNF  and reduced analgesic use at follow-up end. Assessed by different ways, these findings also highlight the long-term clinical impact of the bottom-up effects of EIMS, which is associated with changes in serum BDNF, as well as neurophysiological and psychophysical measures. Overall, this indicates that neuroplastic changes in the pain pathways mediated the clinical result. The impact of EIMS on pain scores is consistent with those of previous randomized clinical trials in which the EIMS using a frequency of 2 Hz induced better effects than sham in a short time in MPS . Both indicate a reduction in the excitability of the motor cortex, as well as lower facilitation of the transmission at corticospinal neurons. These results showed that electrical stimulation of peripheral nerves could modulate cells of cortical networks . This inverse correlation suggests that MEP at baseline indicates higher excitability in a cortico-spinal way, that is part of central sensitization concurs to a higher impairment due to pain. This hypothesis is plausible because, in central sensitization (CS), the secretion of BDNF by astrocytes changes Gamma-aminobutyric acid (GABA-ergic) function, where it can induce excitability rather than inhibition. Indeed, the CS is a dysfunction which involves different mechanisms, such as a selective loss of GABAergic interneurons   . TherebyThis result is clinically relevant and suggests that the increase in serum BDNF levels underlie the therapeutic effect of EIMS. This relationship between the increase in BDNF and pain is consistent with evidence provided by a study in patients with chronic tensional headache treated with electroacupuncture . AnotherFigure 5). Accordingly, it is plausible that it activates the PAG, which is the primary control center for descending pain modulation (The EIMS effect increased the HPT and improved the DPMS as evidenced by the changes in the NPS(0–10) during CPM-task. These findings suggest that the EIMS-intervention induces an effect on the bottom–up inhibitory mechanisms. Its impact in the HPT is in agreement with an earlier study, in which EIMS stimulation of myofascial trigger points (MTP) produced an increase in pain threshold and greater activation on the dorsal midbrain encompassing periaqueductal gray (PAG) . In our dulation . Furtherdulation .Table 2) as in agreement with a previous study the EIMS improved sleep quality in a short-term  Our sample comprises only female because exist extensive literature that they are more prone to activation upon negative emotional responses  as well to physiological factors  . If for In conclusion, these results revealed that ten sessions of EIMS reduced pain score and improved disability due to chronic MPS, as well reduced the analgesic use. They also suggested that the EIMS effects on chronic MPS are mediated by bottom–up regulation mechanisms, enhancing corticospinal inhibition and that this effect involves an increase in BDNF secretion. Additionally, they suggest that the MEP amplitude before treatment and the changes induced by the EIMS in the serum BDNF predicted it’s the long-term impact on the chronic MPS symptoms.IT, FF, and LB were responsible for maintaining the study records. LB and IT participated in the sequence alignment and drafted the manuscript. LB administered the interventions. LA, AD, and AB realized the outcome measures. MZ participated in the sequence alignment. FF participated in the design of the study and performed the statistical analysis. IT and WC conceived the study, participated in its design and coordination, and helped in drafting the manuscript.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.