This study describes how patients with knee or hip osteoarthritis (OA), scheduled for arthroplasty, characterize their pain qualitatively and quantitatively and investigates whether differences exist in pain expression between younger and older patients, and between men and women.One hundred eight patients scheduled for a joint arthroplasty completed the Knee Injury and Osteoarthritis Outcome Score (KOOS) or Hip Disability and Osteoarthritis Outcome Score (HOOS) and a health-related quality of life question. Pain was assessed using the visual analogue scale (VAS), KOOS/HOOS and the Pain-o-Meter (POM) consisting of 12 sensory and 11 affective words (POM-Words). Frequency of analgesics use was assessed and preoperative radiographs were graded. ANOVA was used to test differences in pain expression with age (< 65 vs. ≥65 years), sex, and affected joint as independent factors.Patients < 65 years of age used more affective words (POM) and words with higher affective intensity (median scores 8 (3–39), 5.5 (2–27) respectively), than older patients, despite having less radiographically advanced OA. They also reported more symptoms (KOOS/HOOS) than older patients. However, pain ratings, as measured by VAS and KOOS/HOOS pain, did not differ between younger and older adults. Women reported more frequent analgesics use (45.7 and 26.5% respectively) and rated their pain higher than men (mean POM-VAS = 42 (SD 24) and 31 (SD 19); respectively). No differences existed between sexes for sensory or affective POM-Words, or radiographic grade of OA. With age and sex as independent factors, a significant difference between knee and hip OA remained for sensory POM-words intensity scores.Younger adults scheduled for arthroplasty expressed pain using more affective words and words with higher intensity and had less radiographically advanced OA than older adults. However, VAS and KOOS/HOOS pain subscales could not distinguish the difference in pain expression. Thus, the POM may be a valuable tool for assessment of pain. Total joint arthroplasties (TJA) due to osteoarthritis (OA) are continuously increasing and the greatest rise is found among younger patients –3; a fivSex differences refer to biological differences whereas gender differences arise from sociocultural processes. Data indicate inequality exists by sex  and by gender  in health care –12. ThesThis study aimed to investigate how patients with knee or hip OA, who were scheduled for joint arthroplasty, expressed their pain and whether differences existed in pain expression between younger and older adults (< 65 vs. ≥65 years of age), and by sex. We hypothesized that younger mature adults with knee or hip OA would express pain differently than older adults. Secondarily, we hypothesize that women would express pain differently than men.n = 58) or hip (n = 50) arthroplasty and met the American Society of Anaesthesiologists (ASA) classification for general health status [This cross-sectional study included a convenience sample of 108 patients with knee or hip OA who were scheduled for primary knee . The surgery coordinator asked patients who met inclusion and exclusion criteria to participate. Patients who declined were not registered. Two experienced orthopaedic surgeons  independently assessed all preoperative radiographs using the modified Kellgren & Lawrence classification of OA. The modified Kellgren & Lawrence classification of OA expands the Kellgren & Lawrence radiographic classification , by incoThe POM is a validated instrument used to describe pain in patients with different chronic diseases , 25, 26.The KOOS and the HOOS are reliable and validated disease-specific questionnaires used to measure baseline function, pain and change over time in patients with knee and hip OA , 23 and The EQ-5D is a widely used and validated generic questionnaire provided by the EuroQoL group to measure HRQoL . In thisCategorical data were described using frequencies and percentages. Continuous data were described using means with standard deviations, when normally distributed and median with range, if skewed. Patients were stratified using a cut point of 65 years, as this is the usual retirement age in Sweden (e.g. < 65 years were referred to as younger adults and those ≥65 years as older). T-tests and Mann-Whitney U tests were used, depending on data normality, to calculate differences in POM, KOOS/HOOS and EQ-5D VAS between age and sex groups. To test differences in ordinal outcomes  and joint involved, sex or age group, a Fisher’s exact test or Chi squared test was used. A three-way ANOVA was used to test differences in KOOS/HOOS, POM-VAS and POM-Words, with age group, sex and affected joint as the independent factors. Skewed variables were log-transformed to meet the assumptions of ANOVA. All statistical tests were two-sided, with a significance level of 0.05. IBM SPSS version 22 and 23 were used for all calculations.. All patients had moderate to severe radiographic OA as noted by Kellgren & Lawrence score 3a/b or 4a/b. The mean EQ-5D VAS score was 63 (SD 21). Except for the Sports/Recreation dimension of KOOS/HOOS there were no major differences between those individuals with knee OA compared to those with hip OA in KOOS or HOOS  and aching (G), and the most common affective words were irritating (M), troublesome (O) and tiring (T)s 63 SD 2. Except (3 (1-9) and 2 (1–7) respectively) to describe their pain, and presented with significantly greater intensity sensory scores (8 (2–20) and 6 (0–24)), and intensity affective scores (8 (3–39) and 5.5 (2–27) respectively). Younger patients scored worse for the KOOS/HOOS Symptoms subscale compared to the older (mean 38 (SD 16) and 46 (SD 19) respectively). There were no differences between age groups for the other subscales of KOOS/HOOS, EQ-5D VAS or in pain levels measured with POM-VAS. According to the modified Kellgren & Lawrence OA classification, younger patients had significantly less advanced structural OA than older patients (27 and 52% respectively with grade 4b) (Table Patients under 65 years of age used the words troublesome (O) and excruciating (V) more often to describe their pain than older patients. Younger patients also used significantly more affective words With respect to pain intensity using the POM-VAS, women rated their pain higher (mean 42 (SD 24) versus 31 (SD 19) for men). Women reported they used analgesics more frequently when needed than men . No differences were seen between men and women for KOOS/HOOS scores or EQ-5D VAS. There were no significant differences between men and women in how they described their pain using sensory or affective POM-words: no difference in the number of sensory or affective words used, or the sensory or affective intensity scores. Neither were any differences found in radiographic severity of OA between men and women (Table p = 0.015) and had worse KOOS/HOOS ADL subscale scores (p = 0.037) with sex and age group as independent factors. The difference between men and women in pain intensity measured with VAS remained, with joint and age as independent factors (p = 0.017).With sex and joint involved as independent factors, no differences remained between younger and older patients with respect to KOOS/HOOS symptoms subscale, number of affective words, intensity scores for POM sensory or affective words. Patients with knee OA reported significantly higher intensity scores for sensory words used than those with hip OA  with knee or hip OA scored their pain higher [In this study, younger patients scheduled for a joint arthroplasty had less radiographic severity of OA than the older patients scheduled for a joint arthroplasty. Similarly, Haynes et al. 2016) found that younger patients with knee OA awaiting surgery, had less severe radiographic OA according to the Kellgren & Lawrence score compared to older patients [ found thn higher . We founThere was a difference in pain measured with POM-VAS between sexes and in intensity scores for affective POM-words between ages. In a validation study by Gaston-Johansson et al. , there wConsistent with previous research , women idisease OA representing the structural changes, and the illness OA representing the patient-reported symptoms, and both should be acknowledged when deciding on different treatment methods [illness by discriminating between different types of pain and provide treatment accordingly and further to identify those patients expressing more emotional distress. Hypothetically, incorporating the POM into clinical visits adds another pain dimension and may yield better communication between the patient and the healthcare provider, ultimately improving management of pain [Recently, arthroplasty registries began to focus on postoperative outcomes of TJA in terms of PROs but, as far as we know, they do not have any instrument to measure the emotional experience , 2. The  methods . By usin of pain  and the No a priori power analysis was performed as this was a new area of research and these non-significant results might be explained by the small sample size that could lead to a type II error. Low power could also explain why no differences remained between younger and older patients, with joint and sex as independent factors in a multivariable model as ANOVA. There is the potential for selection bias as we did not examine data from excluded patients, or patients who declined participation. Since we included patients with an ASA classification 1–2 suggesting overall good health, our results may not be generalizable to a larger population but may provide information on how the patients in this cohort express pain. Strengths of this study include: the use of commonly used pain outcome measures in adults with OA in the Swedish Hip and Knee Arthroplasty Registers undergoing TJA (EQ-5D VAS and KOOS/HOOS) [Using the POM outcome measure among patients with knee and hip OA enables the evaluation of pain in a more comprehensive manner (e.g. sensory and affective components) to identify those with emotional distress. Younger patients had significantly less radiographic OA severity but had more joint symptoms than the older patients, and reported greater affective pain expression, suggesting their symptoms had greater emotional impact. Future research should focus on the emotional aspect of pain and its relation to depression/anxiety, joint-related function and postoperative results.


Objective. This study aimed at finding out whether the 3 mm thickness of stabilization splints has positive or negative effects on all temporomandibular disorder (TMD) symptoms. Materials and Methods. The statistical calculation included 25  TMD patients who received 3 mm thickness stabilization splint therapy. They were evaluated according to follow-up treatment period, TMD pain, muscle pain, mouth opening, diet score, and splint usage time per day. Results. There was important treatment success that 22 (88%) of patients were totally healed. There was not any remarkable effect or advancement of splints on total healings of TMDs in first 3 months' period . The mouth opening mean reached 38, 67 mm at 6 months and 41 mm at 12 months with remarkable success. Except one (4%) patient, other 24 (96%) patients had a normal diet score of 3 at the end of splint therapy. There was no correlation between splint usage duration a day and total healing of TMDs. Conclusion. We conclude that 3 mm splint therapy should maintain at least 6 months to achieve remarkable results. Splint should be used at least 12 h a day consistent with our results. Finally, diet score should be incorporated with TMD pain and amount of mouth opening; hence, we advise to use in one term as “total healing.” Temporomandibular disorders (TMDs) encompass internal derangements of the temporomandibular joint (TMJ), abnormalities of masticatory muscles and the neighboring structure of the TMJ, and TMJ-related headache conditions , 2. In aDespite the use of various types of occlusal splints made from a range of soft and hard materials, the most common splint used to treat TMDs, the stabilization splint, remains a valid option highly agreed upon among practitioners . AccordiStabilization splints usually decrease TMD symptoms of pain from internal derangements or of myofascial origin to improve jaw movement and general health. In addition, they increase diet scores and improve disc displacement without reduction through splint therapy  –7.This study aims to determine whether the 3 mm thickness of stabilization splints has positive or negative effects on disc displacement with or without reduction and TMDs symptoms  according to a range of follow-up periods , splint usage time per day (hours), and demographic features of patients.Diagnostic Criteria for Temporomandibular Disorders (DC/TMD) axis I , and radiological findings of organic disease including TMJ detectedTwenty-five TMD patients  received stabilization splint therapy with 3 mm thick splints and were evaluated during the treatment follow-up at 0, 3, 6, and 12 months for the following variables: disc displacement with or without reduction, TMD pain, muscle pain, jaw movement, diet score, splint usage time per day, treatment outcomes, and demographic data. The exclusion criteria for the study included the following:TMD pain: pain was evaluated using the Verbal Analogue Scale (VAS) with 0 indicating no pain, 1 for mild pain, 2 for severe pain, and 3 for the highest level of pain.Muscle pain: masticatory muscles including temporalis, masseter, pterygoid medial, and lateral were evaluated. If pain was present during a 5 second, 1 kilogram palpation of at least one muscle (according to DC/TMD) , 1 indicDisc displacement with or without reduction evaluation: before treatment, MRI and clinical examinations were done; during the follow-up period, only the clinical examinations were done. In addition, disc displacement parameters were evaluated with opening amount by the end of the treatment period.Mouth opening amount: the degree of jaw movement was measured using an interincisal caliper (mm).Diet score: this was evaluated using the VAS with 0 indicating a liquid-only diet, 1 for a soft diet, 2 for soft solids diet, and 3 for a standard diet with no limitations .Splint usage time per day : this was determined by the number of hours the splints had been used during the night or plus night during the day (24 h).Treatment outcome: improvements of TMD pain, mouth opening, and diet score data were considered to determine whether or not an outcome of “total healing” was achieved. A score of 1 indicated total healing; 0 indicated a lack of total healing. In the event that a “0” score was determined, the patient was recommended for advanced treatment of TMDs.t-test was used. When more than two independent groups were analyzed, the analysis of variance (ANOVA) test was used. In addition, for cross tabulation, the Fisher's exact test and chi-squared test both were used for checking with each other outcome. We considered the level of significance to be 5% (p ≤ 0.05).IBM SPSS Statistics for Windows, version 20.0  was used for statistical analysis of the collected data. To compare the two independent groups, independent two-sample TMDs pain: patients' pain scores for the TMJ region were acquired before treatment and also the data in period of treatment were collected as well. By the end of 12 months, 84% of patients were pain-free. A remaining 16% of patients experienced only light pain after 12 months. Muscle pain: before splint therapy, 13 patients (52%) experienced muscle pain. By the end of 12 months of splint therapy, all except 4 patients (31%) had been treated successfully to eliminate muscle pain. Additional results are presented in Disc displacement with or without reduction evaluation: before treatment, 12 patients had disc displacement without reduction, and 13 patients had disc displacement with reduction. By the end of treatment period, remarkable outcome was achieved and is presented in Mouth opening amount: at the beginning of therapy, 12 patients (48%) had limited mouth opening ability . By the end of treatment period, the mouth opening mean reached 41 mm. This shows that 3 mm splint therapy may be the best choice for correcting mouth opening limitations in patients with disc displacement without reduction .Diet score: at the beginning of splint therapy, 3 patients (12%) were able to eat normal diets. After twelve months of splint therapy, all, except 1 patient (4%) who remained on a soft solid diet, were able to eat a normal diet, accounting for 24 patients (96%) .Splint usage time per day: there is no correlation or statistical significance concerning the duration of daily splint usage in relation to total healing .Treatment outcomes: twelve patients completed splint therapy with total healing at 6 months. The remaining 13 patients continued splint therapy through 12 months, and 10 of which attained an outcome of total healing. The remaining 3 patients (12%) had been advised to pursue advanced surgical treatment .Follow-up treatment period: 12 patients were followed up after 3 and 6 months and treated at the same time; 13 patients followed up after 3, 6, and 12 months exhibited full healing except 3 patients who had not completely healed during this period were advised to pursue advanced treatment modalities  no longp=0.450 > 0.05 at 3 months, p=0.154 > 0.05 at 6 months, and p=0.309 > 0.05 at 12 months) process of 3 mm splint treatment of TMD patients. We only suggested that patients use splints for at least 12 hours per day without providing any other counseling, leading patients to use splints for 8 to 20 hours per day. Prior research suggests that stabilization splints should be used at night to meet the necessary daily usage time [The most important result of our study is that the duration of daily splint usage has no correlation with or statistical significance to the total healing . Furthermore, Irving et al. [The parameter of total healing, as defined above by our study, included diet score, TMD pain, and amount of mouth opening. We researched diet score with splint therapy in our study, differentiating our research from other literature on TMDs. Our results concerning diet scores at the end of 12-month splint therapy included 1 patient (4%) on a soft solid diet and the rest of the 24 patients 96%) able to follow a normal diet. In our literature review, we found that Idle et al. % able to examinedg et al.  also clag et al. , we thinOur study showed muscle pain present in 13 patients in the beginning of splint therapy. At early (3 months) and midterm (6 months) stages of splint therapy, the muscle pain was only eliminated in a total of 7 patients (54%), and an additional 4 patients  were pain-free by the end of splint therapy. This means that 31% of myofascial disorder patients with splint therapy have not experienced total pain relief. These results are similar to the findings of Kurita et al.  on the eThere are some limitations of our study like other studies took part in the literature. One limitation of this study is that the work was done retrospectively, analyzing patients' records and files. We evaluated 3 mm splint therapy and its effects on signs and symptoms of TMDs from a distance without control over splint types used  or the use of other conservative treatment options, such as lasers, transcutaneous electrical nerve stimulation (TENS), and self-care counseling. Therefore, our results may provide only unpretending knowledge to the research community due to lacking follow-up data on clinical patients.There were no remarkable effects of splints on total TMD healing in the first 3-month period with a success rate of only 44% (11 patients). There was also no significant difference between 3 months and 6 months .There was no correlation between daily splint usage duration and total healing of TMD signs and symptoms.Researching diet score parameters differentiates our study from other studies on TMDs. In addition, high diet scores were achieved using 3 mm splint therapy.Despite achieving low success rates in early (3 months) and midterm (6 months) treatment periods, by the end of splint therapy (12 months), a success rate of 88% was achieved for 3 mm splint therapy on all symptoms of TMDs, which we consider a successful outcome for a conservative and reversible treatment option.Conclusions drawn from our retrospective research on the effects of 3 mm thick stabilization splints on TMD signs and symptoms are as follows:Finally, TMD signs and symptoms should include TMD pain, amount of mouth opening, and diet score, which encompass our definition of “total healing” of TMDs in our study.


Chronic spinal pain affects many in the United States and is associated with rising healthcare costs - but not improved outcomes. Education and self-care promotion are hallmarks of the recommended approach for this condition. Pain Neuroscience Education (PNE) is a method of educating patients about the neurophysiology of pain that aims to reconceptualize pain from an indicator of damage to an interpretation of input signals by the brain and nervous system. PNE has shown efficacy in controlled situations when delivered by experts, but its effectiveness has not been investigated among trained clinicians in a pragmatic setting.A cluster randomized trial will randomly assign 16 clinic regions to either receive PNE training or continue with usual care. Patients with chronic neck or back pain will be enrolled to provide outcome data. Measures will be collected at baseline, 2 weeks, and 12 weeks. The primary outcome will be the Patient-Reported Outcomes Measurement Information System (PROMIS) Physical Function computer-adapted test (PF-CAT). Pre-specified statistical analyses will compare outcomes between clinic regions assigned to PNE treatment or usual care while using random effects to account for region-level clustering.Pain Neuroscience Education has been shown efficacious for a variety of patient-centered outcomes for those with chronic pain, but it has not yet been investigated outside of controlled settings. This trial has the potential to promote PNE as a low-cost intervention for chronic spinal pain and affect physical therapy education.NCT03168165, registered May 30, 2017.ClinicalTrials.gov identifier  Chronic spinal pain is a very common and costly condition. It affects an estimated 46% of the total population, with low back pain (LBP) being the most prevalent condition . LifetimWith growing healthcare costs and mounting disability, there is increased demand for physical therapists to promote more effective self-management strategies for patients with chronic spinal pain. Education and motivation to engage in treatment are critical components of self-management. Effective self-management requires physical therapists to understand strategies to engage patients in their treatment and facilitate necessary behavior changes. Strategies to promote patient engagement and self-management behaviors and their theoretical underpinnings are not familiar to many physical therapists and may require additional training.Several theories have been proposed to explain human motivation for behavior change , 6. SelfIn SDT, autonomous motivation is fostered by an individual’s sense of autonomy (feeling in control of one’s own behaviors), competence (gaining mastery of tasks), and relatedness (feeling a sense of belonging and attachment) , 8. HealCompetence, or self-efficacy, relates to the degree an individual feels they have control over their situation . Pain seRelatedness refers to the desire to feel connected to others . In healThe strategy being tested in this study to improve patients’ autonomous motivation through enhanced pain self-efficacy and therapeutic alliance is pain neuroscience education (PNE). PNE is an education method used by physical therapists to help patients understand the biology, physiology, and psychosocial factors influencing their pain experience , 18, andOur overall goal is to determine the effectiveness of providing physical therapists with PNE training on patient-centered outcomes  for patients with chronic neck or back pain undergoing care by a physical therapist.This is a two-arm, single-blind, cluster randomized control trial to take place in 16 clinic regions within a large private rehabilitation practice in Atlanta, Georgia and Birmingham, Alabama. Clinic regions are the unit of randomization. We will randomly assign clinic regions to either receive PNE training for physical therapists employed in clinics within the region or usual care (UC) - with no additional training for physical therapists working in the region clinics. The clinic region was chosen over a single clinic for the randomization unit to reduce the potential contamination that may occur when physical therapists work in more than one clinic within a region. Randomization of clinic regions will be stratified by clinic region size and a measure of the region’s clinical outcome for LBP. Clinic region size was based on the average number of new evaluations per week during the period February 2016 – February 2017 over the participating clinics within the designated clinic region. The region’s clinical outcome for LBP is based on the average rank of the region’s clinics among other clinics in the company based on the Oswestry Disability Index , a commoPhysical therapists working in clinics in participating regions will receive either PNE training or no additional training based on the random assignment of their clinic region. Outcomes will be assessed on consenting patients with chronic neck or LBP treated within these clinics. We will recruit patients meeting our eligibility criteria who are scheduled for physical therapy evaluation at a clinic within a participating region. Because the intervention is given to physical therapists, potentially eligible patients are asked to consent to provide outcome measures for the study, consistent with a cluster-randomized design. Physical therapists will provide informed consent to participate in the project and participate in training procedures. Other than the training to provide PNE (or not), there will be no attempts to direct physical therapist treatment or duration of care in any way as a result of participation in this study.Patient participants in this project must be age 18–75 at time of their first session with a physical therapist, their primary reason for seeking physical therapist care must be low back and/or neck pain, and they must meet the NIH definition of chronic spinal pain  , recent surgery, pregnancy, or concerns about a red flag condition. We will track recruitment of patients into the project and reasons for ineligibility. Patients who do not meet the eligibility criteria or choose not to enroll will not have their physical therapist care impacted in any way. These patients are compensated $15 for each of the assessment time points completed (up to $45). This is dispensed in the form of an electronic gift card. Due to the low risk nature of this trial, a cover letter consent will be utilized instead of requiring a signed consent document.Physical therapist participants will be recruited from clinics in the 16 participating regions. Participating physical therapists must not have previously received formal training in pain neuroscience education totaling more than 8 h of instruction. They must not plan to leave the company during the recruitment period or hold a position that requires that they see patients in both control and intervention clinic regions.These criteria are designed to recruit a group of physical therapists without prior exposure to PNE who treat patients within a single recruitment region of the study. Physical therapists who do not meet these criteria or who choose not to participate will not have their employment impacted, and they may choose to participate in training along with their primary clinic affiliation. We anticipate that new physical therapists will join participating clinics during the course of this project. We will provide an interim training session during the recruitment period as an opportunity to train newly-hired physical therapists working in clinics randomized to receive PNE education and provide therapists and additional opportunity to join the study and receive training. We will not recruit patients from any physical therapist until he or she has consented to participate and has received the appropriate training. If a physical therapist moves within the company between clinic regions, we will discontinue recruiting patients seen by the therapist unless he or she moves to a region randomly assigned to the same group as his or her previous region. The physical therapists receive 16 continuing education units for completing the education course as an incentive for participating. The physical therapists in the control clinic will also be trained at the end of the project. Physical therapists will also be consented via a cover letter consent form due to the low risk nature of their participation.Patient participants for this study will be identified by front office staff when requesting to be scheduled for an initial physical therapist evaluation. We will supply the front office staff with a scripted message notifying the patient that they may be eligible to participate in a research project and ask permission for a researcher to contact them. A secondary method to offer participation in the study will use the clinics’ electronic medical scheduling system , which allows custom reports to identify those scheduled for initial examinations with a diagnosis of neck or back pain. Lists of patients who meet this initial eligibility will be emailed by the research team to inform them of their potential eligibility and provide an opportunity to opt-out of being contacted. The research team will call the patient after 1 day to explain the study if they do not opt-out. Informed consent will be obtained by email with a consent cover letter. A patient is considered enrolled in the study when he or she begins completing the online baseline measures.All project data will be collected using REDCap, an electronic data management system. This allows all data to be directly entered electronically by all subjects, patient and physical therapists, at all time points. REDCap automated process sends an email with a patient-specific link to all questionnaires. This minimizes the risk of bias based on group allocation from the investigators and reduces burden on any clinic or study personnel.At baseline, the patient will provide demographic information including age, sex, race/ethnicity, employment status, and general medical and current history of symptoms.The primary outcome will be physical function (PF), assessed using computer-adaptive test methods (CAT) developed by the Patient-Reported Outcomes Measurement Information System (PROMIS). PROMIS is an NIH-sponsored project using advanced psychometrics to develop patient-reported outcome measures with improved reliability, validity, and responsiveness , 36. PhySecondary outcome measures to be collected will include the PROMIS Pain Interference CAT, which assesses the consequences of pain on daily life. The Pain Interference CAT is highly reliable and validity based on correlation with other validated tools . The PaiOther measures to be collected in the study will include potential covariates. The Numeric Pain Rating Scale (NPRS) ranges from 0 (no pain) to 10 (worst imaginable pain) as a measure of pain intensity. The Pain Catastrophizing Scale (PCS) is used to quantify catastrophic thoughts regarding pain. Scores range from 0 to 52, with higher scores indicating higher levels of pain catastrophizing . The Gloreview the most important concepts from online training; 2) demonstrate incorrect vs effective PNE approaches using actual case examples, 3) practice proper assessment and PNE implementation using role-playing, and 4) Discuss how to implement a PNE approach in conjunction with the therapists’ current therapeutic approaches of manual therapy and exercise.Physical therapists working in clinic regions randomized to receive PNE education will be trained using both in-person and online content. Latimer and colleagues  used a 1The total education content will be approximately 16 h. Physical therapists will be required to complete the online modules, attend the 6-h in-person practice session, score > 90% on the Neurophysiology of Pain Questionnaire, and score > 90% on a written course examination. A portion of the in-person session will be used to provide instructions in administrative aspects of the study.In order to monitor fidelity of the PNE provided by physical therapists in the training group, we will ask patients consenting to participate if their physical therapist provided education that equated pain with a threat and not an indicator of injury or damage at the 2-week assessment. This question will help to assess if PNE was provided in a manner that the patient recalled. We recognize the potential bias of patients not recalling that PNE was actually provided; however, we chose this strategy because if a patient is unable to remember the primary message of PNE after only 2 weeks, it is unlikely that it was provided in a manner likely to impact outcomes. In addition, the Neurophysiology of Pain Questionnaire will also be given to patients at baseline and at the 2-week time point to test patients’ knowledge of pain mechanisms. This will allow further exploration of our PNE training strategy’s ability to improve patient understanding of pain. Bi-weekly emails will be sent to the PNE-trained physical therapists highlighting an aspect from their training to encourage fidelity and maintenance of implementation of the PNE approach.Pre-treatment baseline patient and clinic characteristics will be compared between randomized groups to assess chance imbalances. If differences are found, these variables may be included as covariates in sensitivity analyses. In accordance with the intentionto-treat principle, all patients will be analyzed in the group to which their physical therapist was randomized regardless of compliance or fidelity. A “per-protocol” secondary analysis will be considered if fidelity to providing PNE is a concern.For the primary outcome (PF-CAT), we will apply a linear mixed model to compare the primary PROMIS PF-CAT score at 12 months between the randomized groups while including the baseline PROMIS PF-CAT as a fixed effect covariate, with nested random effects for provider and clinic region to account for clustering by provider and the clinic regions. If substantial imbalances are detected in patient factors at baseline, these factors will be added as additional covariates in sensitivity analyses.Statistical significance will be evaluating using a 2-sided α = 0.05 for both primary and secondary outcomes without adjustment for multiple comparisons. Intent-to-treat principles will be used for the analysis with all participants analyzed based on the treatment group of the clinic in which they received care - regardless of the therapist’s compliance with providing the PNE intervention. Sensitivity analyses based on fidelity in providing PNE or based on spinal region (neck or low back) may be considered. In addition, we will explore between-group differences from baseline to 2 weeks to examine immediate effects of treatment by a physical therapist trained to provide PNE.We determined our sample size in order to detect a clinically relevant important effect on the PROMIS PF-CAT after 12 weeks with 80% power while accounting for clustering due to clinic regions. The literature on minimum clinically important differences for PROMIS scores is limited for spinal pain patient populations. In one study of 170 patients with LBP receiving spinal injections, Schalet  reportedChronic spinal pain is a challenging condition to treat for physical therapists. Pain Neuroscience has shown efficacy in trials with high internal validity , 23–27. While PNE has been shown efficacy in more controlled studies with greater internal validity , 23–28, One limitation of this study, which is common to pragmatic studies, is balancing internal validity with the need for greater generalizability. We will monitor fidelity to the intervention by querying patients about the key message of PNE, but a more robust fidelity assessment  would diminish generalizability of our results. Consistent with a pragmatic approach, we chose a cluster-randomized design to minimize the potential bias due to contamination from physical therapists with different study-related training working in the same clinic. We chose to randomize clinic regions instead of individual clinics because it is not uncommon for a physical therapist to work in more than one clinic within a region. While this design minimizes concerns for contamination, it reduces the number of units available for randomization and therefore required a greater number of patient participants in the study to obtain adequate statistical power. The researchers only interact with study participants in our study through email and phone correspondence. This could have an effect on study retention, but is consistent with a pragmatic approach.


Spasticity is a muscle tone disorder associated with different neurological conditions. Spasticity could be associated with pain, high disability, poor functional recovery, and reduced quality of life. Botulinum neurotoxin type A (BoNT-A) is considered a first-line treatment for spasticity and, more recently, it also represents a therapeutic option for various chronic pain conditions. In this open label study, we aim to evaluate the effect of the BoNT-A on the spinal nociception in patients affected by spasticity of the lower limbs with associated pain with predominantly neuropathic features. Ten patients with stroke, 10 with multiple sclerosis and 5 with spinal cord injury were enrolled in the study. They were tested with clinical scales , numerical rating scale (NRS), modified Ashworth scale (MAS) and with the nociceptive withdrawal reflex at lower limbs to explore the spinal temporal summation threshold at baseline and 30 day after BoNT-A injection. OnabotulinumtoxinA (50 to 200 units per site) was injected in the lower limb muscles according to the distribution of spasticity. No significant differences were found at baseline for neurophysiological features across groups. After the BoNT-A injection, we recorded a significant reduction in MAS and NRS scores. Regarding the neurophysiological parameters, we described a significant increase in the temporal summation threshold after the BoNT-A injection. Our data supports the hypothesis that peripherally injected OnabotulinumtoxinA modulates the excitability of spinal cord nociceptive pathways. This activity may take place irrespective of the effect of the drug on spasticity. Spasticity is a motor disorder characterized by a velocity dependent increase in muscle tone, with exaggerated tendon jerks, resulting from hyper-excitability of the stretch reflex, and is one component of the upper motor neuron syndrome . There aUp to 65% of patients who develop spasticity also present painful symptomatology . Pain maBotulinum neurotoxin type A (BoNT-A) is considered a safe and effective treatment for spasticity  and moreIn a recent study, we demonstrated that, in subjects with upper limb spasticity, the BoNT-A injection reduced in parallel the degree of spasticity and the size of the nociceptive withdrawal reflex (NWR) response of the upper limb, irrespective of the site of injection . The NWRThe aim of the study was to evaluate the effect of BoNT-A on the spinal nociception in patients affected by spasticity of the lower limbs who reported pain with predominantly neuropathic features . To thisTen patients with stroke , 10 with MS  and 5 with SCI  were studied. All clinical data are reported in When the clinical and psychophysical outcomes were considered, a significant reduction in modified Ashworth scale (MAS)  and numerical rating scale (NRS)  mean values was found in the patients overall considered for T1 vs. T0 comparison . We alsoFor neurophysiological outcomes, no significant differences were found at T0 between patient groups except for area . A signiNo significant correlation was found between neurophysiological and clinical variables, either in the overall population or in single patient groups.The results of the present study can be summarized as follows: OnabotulinumtoxinA injection (1) significantly increased the NWR TST in patients with spasticity and pain with predominantly neuropathic features; (2) significantly reduced the overall pain perception and; (3) significantly improved the MAS scores in the lower limb at T1. In parallel, we observed a nearly significant reduction in neuropathic severity pain score after OnabotulinumtoxinA injection.As expected, our data confirmed the efficacy of OnabotulinumtoxinA in reducing spasticity and related overall pain sensation in a wide range of pathological conditions, including stroke, SM and SCI . The newThe observed increase in TST of NWR supports the hypothesis that peripherally injected OnabotulinumtoxinA decreases central nervous signaling, thus reducing the WDR neuron activity  and the Indeed, the reduction of the NPSI scores, even if it did not reach the statistical significance, might represent the clinical subjective counterpart of the reduction of the sensitization of the spinal nociceptive neurons. We speculate that the lack of statistical significance in NPSI scores could be related mostly to the sample size and the clinical heterogeneity of patients.Regarding the relationship between OnabotulinumtoxinA injection, pain and spasticity, we are aware that the reduction of the spasticity can influence the anti-nociceptive effect of the OnabotulinumtoxinA on the NWR. However, recent evidences suggest that central post-stroke pain relief and spasticity improvement after OnabotulinumtoxinA injection were independent from each other, and with a different and typical temporal profile ,36.Only a few studies have investigated the effect of the botulinum toxin administration on the nociceptive reflex responses in animals, as well as in humans.In animals, Favre-Guilmard et al.  demonstrSimilarly, we recently demonstrated  that in However, as the presence of muscle relaxation can overestimate the anti-nociceptive effect of the OnabotulinumtoxinA on the NWR. In the present study, to better understand the antinociceptive effect of the OnabotulinumtoxinA and to minimize the effect of the muscle relaxation in NWR responses, we studied the effect of the OnabotulinumtoxinA on the TST of the NWR, as it represents an objective evaluation of the functional activity of nociceptive spinal neurons. In addition, we avoided injecting the muscles directly involved in the reflex response such as the biceps femoris or adjacent thigh flexor muscles and we injected more distal muscles of the leg.Our results showed that NWR area was not significantly reduced between T0 and T1 as well as the NWR Th was not significantly increased, demonstrating that the spasticity improvement per se was not able to significantly influence the nociceptive response. In parallel, the significant increase of the TST of the NWR after the OnabotulinumtoxinA injection indicated a significant inhibitory effect on sensory/nociceptive spinal neurons.Our data show that OnabotulinumtoxinA injection improved clinical and neurophysiological outcomes in patients affected by neurological disorders causing spasticity and pain with neuropathic characteristics. We found no correlation between the degree of spasticity and the neurophysiological parameters at T1, which suggests that OnabotulinumtoxinA may have a direct effect on the excitability of spinal cord nociceptive pathways, irrespective of the effect on spasticity.Limitations of the present study included the small sample size, the open label design of the study and the heterogeneity of the patients that suggest caution in the interpretation of the present findings.The enrollment of patients who were not taking drugs for spasticity and pain has probably contributed to select subjects with a relatively low NPSI and NRS scores, which limits the generalizability of our findings.Our results encourage further studies to better characterize the modulation of the central nociceptive pathways induced by OnabotulinumtoxinA injection, to further support its role as a pharmacological treatment of pain with neuropathic component ,39. MoreThe study was approved by the IRCCS Mondino Foundation Ethics Committee  and was carried out following the guidelines for proper human research conduct in accordance with the Helsinki Declaration of the World Medical Association and its revisions. All the participants gave their written consent and were informed that they could withdraw from the experiments at any time.Patients with previous stroke, either ischemic or hemorrhagic, MS and SCI with evidence of spasticity and pain with neuropathic features  were recruited at Neurorehabilitation Unit of C. Mondino National Neurological Institute, Pavia, Italy.The inclusion criteria were: (a) Male or female patients aged between 20 and 75 years; (b) onset of spasticity at least 6 months before; (c) spasticity in one or both lower limbs with a modified Ashworth scale (MAS) score of at least 2 in at least one lower limb; (d) residual motor function in the lower limb muscles ; (e) last BoNT-A injection at least 6 months before.The exclusion criteria were: (a) Severe osteoarticular degenerative or inflammatory disease in the lower limbs, myopathy or polyneuropathy that could hinder NWR acquisition; (b) contraindications to the use of BoNT-A ; (c) psychiatric disorders; (d) Beck depression inventory (BDI) score > 19/63 (e) moderate to severe cognitive impairment ; (f) inability to communicate with investigators or to answer the questionnaire.No change in the treatment schedule was allowed from T0 to T1. No drugs or other interventions for neuropathic pain and spasticity ,9,40 werAt enrollment the patients underwent a complete clinical evaluation including recording of personal and clinical data, medical history and neurological examination. Demographic and clinical data are summarized in Neurophysiological evaluation, including sensory threshold (ST), NWR threshold (Th) and TST of the NWR, was performed on the lower limb that was affected by spasticity, or the more severely affected one in case of bilateral spasticity by using a validated method . PatientThe transcutaneous electrical stimulation consisted of a train of five individual 1-ms constant current pulses delivered at 200 Hz  and perceived as a unique stimulus. Each train was released in a random fashion every 25–40 s . Electromyographic reflex responses were recorded from the capitis brevis of the biceps femoris via surface electrodes (Ag/AgCl) using a bandpass filter between 3 Hz and 3 kHz . The analysis time was 300 ms with the sensitivity set at 100 mV. Each reflex response was rectified and integrated in the 80–130 ms post-stimulus interval .The ST was determined on the basis of a sequence of stimuli of increasing intensity in 1 mA steps randomly delivered every 10–20 s. Subjects were asked to indicate verbally the stimulation level at which they became aware of sensory sensations. The staircase method was used to evaluate NWR threshold (Th), defined as the intensity of stimulation able to generate a stable reflex response by an amplitude exceeding 20 µV for more than 10 ms in the 80–130 ms time window post stimulus. The area under the curve (area) of the NWR responses at Th were automatically measured and expressed as ms × mV. The area was preferred to the reflex amplitude because it represented a more reliable parameter of the spinal motoneuron reflex activation . SubjectTo obtain the TST of the NWR, the sural nerve was stimulated using the previously described pulse train of 5 stimuli of 1 msec delivered at 200 Hz and repeated 5 times at a frequency of 2 Hz . The curOnabotulinumtoxinA in doses ranging from 50 units to 200 units per site were injected with electromyographic guide according to patient’s weight and the degree of spasticity in the following muscles: sSoleus, gastrocnemius medialis, tibialis posterior, flexor digitorum brevis and adductor longus.This was an open label study. After the enrollment, a first clinical and neurophysiological evaluation was performed before the OnabotulinumtoxinA treatment (T0). The same clinical and neurophysiological evaluation was carried out 30 days after OnabotulinumtoxinA injection (T1). Study procedures were performed by different physicians: Enrolment (CT), clinical and neurophysiological acquisitions (EB), OnabotulinumtoxinA injection (EA). The separation of roles was put in place to limit the impact of individual beliefs upon the neurophysiological parameters. In this way, the clinical neurophysiologist was not informed of the type and timing of the treatment the patients had undergone.The size of the sample was calculated considering the modification of the TST (T1 vs. T0) in the overall population as the primary outcome. The following parameters were used: Confidence interval (two sided) 95%; power 80%; difference between groups of 2.0 mA; standard deviation of 3.0 mA. The minimum suggested sample size was 20; we decided to enroll 25 patients in order to control for drop-outs.The Statistical Package for the Social Sciences (SPSS) for Windows, version 19.0, was used for all analyses .Mean values of demographic, clinical, neurophysiological  and psychophysical variables (NRS) clustered for group of patients  were entered in the statistical analysis.One-way analysis of variance (ANOVA) was used to compare the mean values of the clinical and demographic characteristics, neurophysiological and psychophysical baseline variables between the different groups . Paired t-tests were performed to compare the mean values of clinical, neurophysiological and psychophysical variables between T0 and T1.All values were reported as means ± S.D. Pearson’s correlation was used to test correlations among electrophysiological and clinical variables.p < 0.05 (two-tails) for all the tests.The level of significance was set at


Fibromyalgia (FM) is a generalized chronic pain condition associated with a variety of symptoms, including altered cognitive and emotional processing. It has been proposed that FM patients show a preferential allocation of attention to information related to the symptoms of the disease, particularly to pain cues. However, the existing literature does not provide conclusive evidence on the presence of this attentional bias, and its effect on cognitive functions such as inhibitory control. To clarify this issue, we recorded the electroencephalographic activity of 31 women diagnosed with FM and 28 healthy women, while performing an emotional Go/NoGo task with micro-videos of pain, happy, and neutral facial expressions. We analyzed behavioral data, performed EEG time-frequency analyses, and obtained the event-related potentials (ERPs) N2 and P3 components in NoGo trials. A series of self-reports was also administered to evaluate catastrophic thinking and the main symptoms of fibromyalgia. Pain expressions were associated with longer reaction times and more errors, as well as with higher theta and delta power, and P3 amplitude to NoGo stimuli. Thus, behavioral and psychophysiological data suggest that increased attention to pain expressions impairs the performance of an inhibitory task, although this effect was similar in FM patients and healthy controls. N2 amplitude was modulated by type of facial expression (larger to pain faces), but only for the control group. This finding suggests that the presentation of pain faces might represent a smaller conflict for the patients, more used to encounter pain stimuli. No main group effects were found significant for N2 or P3 amplitudes, nor for time-frequency data. Using stimuli with greater ecological validity than in previous studies, we could not confirm a greater effect of attentional bias toward negative stimuli over inhibitory performance in patients with FM. Studying these effects allow us to better understand the mechanisms that maintain pain and develop intervention strategies to modify them. Fibromyalgia (FM) is a chronic pain condition of unknown etiology, characterized by the presence of generalized musculoskeletal pain, in addition to fatigue, poor sleep quality, anxiety, depression, and altered cognitive and emotional processing. It has been proposed that FM patients show a preferential allocation of attention to information related to the symptoms of the disease, particularly to pain cues. This idea has been discussed as hypervigilance and, more recently, as attentional bias (AB) ,—that may not represent the patients' real concerns or may not be relevant to the population studied—, and the exposure time of stimuli have been underscored as critical variables  using 500 ms micro-videos, and proposed a different strategy to assess the effect of AB. Our objective was to investigate how attention toward pain-related information affects response inhibition, one of the executive functions altered in fibromyalgia  to clarify whether fibromyalgia patients show higher interference of attention toward pain stimuli over inhibitory control ; (2) to assess whether the amplitudes of N2 and P3 to painful faces are related to the core symptoms of fibromyalgia . Given that previous studies have reported that attention to negative emotions impairs inhibition . In addition, healthy controls (HCs) should not have any chronic pain condition. For ethical reasons, patients were not asked to withdraw prescribed medical treatments. Demographic characteristics of the groups are shown in Table The participants gave their written informed consent for their participation in the study, approved by the Galician Autonomous Committee for Research Ethics (2013/582), and conducted in accordance with the Declaration of Helsinki.Clinical and sociodemographic data on the participants were obtained via a semi-structured interview.ad-hoc to evaluate the main symptoms of FM, as well as the general health condition of the participants. The VAS were administered in paper-and-pencil format and consisted of 10 cm horizontal lines in which the participants had to indicate their condition on the following variables: pain, health status, stiffness, fatigue, mood, headache, and sleep quality. All of them were presented in a manner that the left end indicated the best condition and the right end the worst.A series of visual-analogical scales (VAS) were created Beck Depression Inventory  questionnaire that comprises 30 items related to complaints in different cognitive domains. The MFE-30 Total score (range 0–120) was calculated as the sum of all items. This score was ranked into four categories: 0–7, 8–35, 36–50, and over 50, indicating optimal performance, normal, mild deterioration, and moderate deterioration, respectively.The Spanish version of the The above instruments were used to explore the core clinical symptoms of fibromyalgia, including also variables, such as catastrophism or perceived stress, which may be relevant for the study of attentional bias toward pain-related information. Since inhibition is an executive function, we also explored whether the indices obtained in the Go-NoGo task were related to the subjective cognitive complaints reported by the patients.Edinburgh Handedness Inventory  were presented to them in three blocks. In each block, participants were asked to press a button with their index finger button as quickly as possible whenever a specific expression  was displayed, and inhibit this response when the expression displayed was different. Each block consisted of 40 Go trials and 40 NoGo trials. The interval between stimuli was 1.9–2.3 s. The order of the blocks was balanced among the participants, who had a resting period between blocks. Prior to registration, 10 practice trials were presented with videos different from those used in the task, to ensure that the instructions were fully understood and that facial expressions were correctly identified.To capture the electroencephalographic signal, we used an actiCAP elastic cap with 32 electrodes placed according to the 10–10 International System and a Brain Vision actiCHamp amplifier (Brain Products Inc.). The ground was placed at FPz, and reference at FP1, which was reinstated after re-referencing. One additional electrode was placed 1 cm below the right eye, and vertical ocular movements were monitored by calculating the difference between this electrode and FP2. Electrode impedances were kept below 10 kΩ, and the signal was digitized at 500 Hz with an on-line bandpass filter of 0.01–200 Hz, and a notch filter at 50 Hz.SD = 1.4; mean HC = 2.77, SD = 1.2; t(57) = 0.56; p = 0.58] . In addition, to avoid group bias during data pre-processing, the researcher was blind to the group to which each of the EEG recordings belonged. The EEG was re-referenced using the Reference Electrode Standardization Technique (REST)  Yao, , a matheST) Yao, . The basST) Yao, . Given tST) Yao, . The powWe also measured the mean amplitude of P3 at the Cz electrode in a window from 350 to 600 ms, and the mean amplitude of N2 at the Fz electrode in a window from 250 to 340 ms only in NoGo trials. The selection of electrodes was based on previous reports  as between-subject factor, and Facial Expression  as within-subject factor, were performed for behavioral indices (reaction times and hits), for midfrontal theta, posterior theta, and posterior delta power, and for the amplitude values of P3 and N2. The Bonferroni correction method was applied for post-hoc multiple comparisons. Associations between ERPs amplitudes and clinical variables for FM patients were quantified using Pearson correlations. To overcome the problem of multiple comparisons in the correlations, the False Discovery Rate (FDR) correction—using the “fdr” function of EEGlab—was applied.Means and standard deviations were used to describe the quantitative variables, while absolute frequencies and percentages were used for the qualitative measures. Differences between FM and HC groups in clinical and sociodemographic variables were analyzed using Student's All statistical analyses were performed using SPSS version 20 .There were no significant differences between the FM and HC groups in terms of age, education, menopausal status, or laterality Table .Pain Catastrophizing Scale (PCS), FM patients obtained an average score of 23.72 (SD = 15.26) and the control group an average of 11.00 (SD = 8.93). It should be noted that the groups differed in all the 3 factors that comprise the scale. As for the Beck Depression Inventory (BDI), we also found significantly higher means for the FM group (mean = 20.16) compared to the control group (mean = 10.17). Patients also showed worse sleep quality in the Pittsburgh Sleep Quality Index (PSQI) than healthy controls (13.04 vs. 5.75), broader subjective cognitive complaints in the Memory Failures of Everyday Questionnaire (MFE-30) (50.95 vs. 26.16) and higher stress levels in the Perceived Stress Scale (PSS) compared to the control group (31.78 vs. 21.71).Regarding clinical variables, the comparisons between the FM and HCs were statistically significant for all the scales and subscales analyzed Table . ConcernThe behavioral data obtained by FM patients and HCs in the Go and NoGo trials for happy, pain, and neutral stimuli are shown in Table F = 18.34; p < 0.001; ηp2 = 0.243; Pain = 650 ± 118 ms; Neutral = 617 ± 123; Happy = 590 ± 90], as well as for the percentage of correct answers in both the Go  and NoGo  trials. A posteriori contrasts showed that, in the Go trials, faces of pain were associated with slower reaction times than neutral (p < 0.001) and happy (p < 0.001) faces and, moreover, they were also associated with more errors than neutral (p < 0.001) and happy (p < 0.001) faces in both groups. Happy faces showed the fastest reaction times and the largest hit percentages. There was no significant interaction between emotion and group. As for the NoGo trials, pain faces were also associated with the worse hit percentages in both groups (p < 0.001). In this case, when it comes to inhibiting the response, neutral stimuli were associated with the best performance.There was a significant effect of Facial Expression for the reaction times in Go trials  or interaction  were observed.For time-frequency data  = 4.21; p = 0.017; ηp2 = 0.069; Pain = 2.34 ± 1.42; Neutral = 1.94 ± 1.31; Happy = 1.81 ± 1.55], with significant differences only between pain and neutral conditions (p = 0.040) in pairwise comparisons. No Group difference  or interaction  were found significant.Posterior delta activity (2–4 Hz)—measured over O1 and O2 electrodes and from 100 to 600 ms—showed a main effect of Facial expression . Again, post-hoc comparisons showed differences between pain and neutral (p = 0.043) and pain and happy conditions (p = 0.009), with no significant Group effect  nor Group × Facial expression interaction .Posterior theta oscillations (4–7 Hz)—measured over O1 and O2 from 100 to 400 ms—also showed an effect of Facial expression . Subsequent contrasts showed significantly larger P3 amplitude for pain (mean = 3.41 ± 3.09 μV) than for happy faces (mean = 2.89 ± 2.77 μV) (p = 0.027). No significant Group effect was found significant.For P3 amplitude, the results showed a significant effect of Facial Expression . A posteriori contrasts showed significant differences between pain (mean = −5.02 ± 0.66 μV) and neutral faces (mean = −4.10 ± 5.88 μV), (p = 0.001); and between pain and happy faces (mean = −4.18 ± 0.59 μV), (p = 0.005), only for the control group. For the patients' group, there was no difference in the amplitude of N2 among any emotional category. The waveforms obtained in the NoGo trials at Fz and Cz electrodes for all the stimuli are shown in Figure For N2, the ANOVA showed a significant Facial Expression × Group interaction for the amplitude of this component [p-value < 0.05: the amplitude of N2 and the quality of sleep measured with the PSQI , and the amplitude of P3 and the level of pain assessed by the VAS . However, none of these 2 correlations survived the FDR correction. No other correlation between ERPs and clinical indices was found significant.To clarify whether there is a relationship between the amplitude of the N2 and P3 components for pain faces and the clinical variables, Pearson correlations were performed with the FM patients' data. Two of the correlations showed a The objective of this study was to test whether patients with fibromyalgia (FM) show a larger interference of attention toward pain-related stimuli over inhibitory control. We recorded brain electrical activity during a Go/NoGo emotional task, in which the participants had to respond or withhold the response to dynamic images of faces with different expressions. Given the dynamic nature of the stimuli, we performed EEG time-frequency analyses  and also obtained the ERPs N2 and P3 in NoGo trials.First, our data support that attention to pain faces interferes with response inhibition. Behaviorally, pain expressions were associated with a higher percentage of errors and slower reaction times. This result suggests that pain-related stimuli are more conflicting and may engage more attentional resources to their processing, resulting in longer reaction times. Nevertheless, this effect was not different in patients and controls.Pearce and Morley  were pioThe study of AB in patients with FM has also yielded contradictory findings. González et al  used an Although we used a different strategy—to analyze the influence of attention to pain over inhibitory control—our behavioral results are in line with the conclusions of the meta-analysis conducted by Crombez et al.  that theTo better know the temporal characteristics of neural activation involved in response inhibition, we recorded EEG during the performance of the task and analyzed it with two different methodologies. Since the ERPs components may be reflecting overlapping theta and delta activity (Harper et al., Our results are in line with a recent study by Sitges et al.  who compThe only significant electrophysiological difference between the groups is related to the amplitude of N2, for which we found an interaction of group with the type of facial expression. Only for healthy participants, N2 showed differences between pain and both neutral and happy faces. The N2 component obtained in the NoGo trials has been linked to inhibitory processes, and more recently, to conflict detection (Falkenstein et al., Alternatively, this result could also indicate a delay in emotional processing in the patients, as about 300 ms post-stimulus they have not yet differentiated the emotional content. However, the lack of a significant difference in reaction times between patients and healthy controls does not seem to support this explanation. Finally, it could also be interpreted as less emotional reactivity in patients with fibromyalgia. In this regard, there are studies that corroborate that alexithymia, a personality construct characterized by difficulty in identifying and communicating feelings Taylor, , may plaTo elucidate the relationship between the ERPs obtained in the presence of painful faces and clinical variables, we performed a correlational analysis for the FM group. Although a priori the data suggested two significant correlations, these did not survive the FDR correction. Contrary to what might be expected, we found no correlation between variables such as catastrophism or depression and the ERPs. In this vein, Sitges et al.  did not Our study adds to a growing body of research that has failed to find evidence of an attentional bias toward pain-related stimuli in patients with fibromyalgia other than the present in healthy subjects. More sensitive paradigms may be necessary to elicit the response bias toward pain stimuli. Also, and despite using dynamic images instead of written words, our stimuli may not have had enough impact, and might not have interfered with emotional processing. Perhaps the impact would have been greater if the images referred to pain experienced by the subject himself, and not to the pain of others since some authors suggest that biases in information processing are increasing and may even be dependent on self-referential coding (Pincus et al., Attention influences subjective pain (Miron et al., As limitations of the present study, we may underscore the fact that we used equiprobable Go and NoGo trials. Although this is rather frequent in the literature, Wessel  found thMP-M, AG-V, and MC contributed to the study concept and design and wrote the paper. MP-M and AG-V performed the patient's assessment and EEG recordings. All authors approved the final version of the manuscript for submission.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.


This study investigated the plasma fentanyl concentration and efficacy of transdermal fentanyl patch (TFP) (25 μg/h) in the management of acute postoperative pain.Patients undergoing laparoscopic cholecystectomy were randomly allocated to 2 groups. The TFP group (n = 30) received a single TFP 25 μg/ h to the anterior chest wall 14 h before operation. The IV group (n = 30) received a placebo patch. After the operation, intravenous fentanyl infusion (25 μg/h) was begun with loading dose 25 μg in the IV group and only normal saline in the TFP group. Plasma fentanyl levels were measured at admission, 1, 6, 12, 24, and 48 h postoperatively. Pain severity and adverse effects were evaluated too.The fentanyl level peaked 1 h after operation in the TFP group (3.27 ± 0.34 ng/mL) and 24 h postoperatively in the IV group (2.9 ± 0.42 ng/mL). Pain scores and the use of rescue analgesics were not significantly different between 2 groups. Respiratory depression was not happened in both groups.http://cris.nih.go.kr, KCT0002221).The TFP (25 μg/h) affixed 14 h before surgery reached a higher constant concentration than the same dose setting of a constant IV infusion of fentanyl after surgery. Although the concentration of fentanyl was higher than those of previous researches, there was no respiratory depression. But, there was no advantage of reducing pain score and the use of rescue analgesics. Clinical trial registration: (available at:  Although the efficacy and safety of TFP for acute postoperative pain management have been investigated, studies measuring plasma fentanyl concentration were too old and recent studies assessed the TFP for postoperative pain control relied on a pain score, rescue analgesic consumption, and the incidence of adverse effects.–9Postoperative pain management is a major concern in surgical patients and inadequate postoperative pain relief is their most frequent complaint. The optimal analgesic modality should be effective, easy to use, safe, and economical. However, adequate pain control without the adverse effects remains challenging. Postoperative pain is commonly managed by intravenous patient-controlled analgesia (IV-PCA) using opioids, such as fentanyl, morphine, or meperidine.The aim of this study was to assess the plasma fetanayl concentration after TFP (25 μg/h) applied and the efficacy of a TFP applied 14 h before surgery compared to that of an IV constant fentanyl infusion in the management of postoperative pain by pain scores and adverse effects after laparoscopic cholecystectomy.22.1http://cris.nih.go.kr, KCT 0002221). The inclusion criteria were patients from 20 to 80 years of age who were scheduled for elective laparoscopic cholecystectomy under general anesthesia with American Society of Anesthesiologists (ASA) physical status I–II from October in 2015 to May in 2016. Patients with a history of allergy to fentanyl, major organ disease, a history of alcoholism or drug abuse, obstructive sleep apnea, fever, or obesity (body mass index > 35 kg/m2) were excluded.This prospective study was approved by the Institutional Review Board of Hallym University Chuncheon Sacred Heart Hospital (No. 2015-93). Written informed consent was obtained from all enrolled patients and conducted according to the Declaration of Helsinki standard. The protocol of this clinical trial was registered on the Clinical Information Service (available at: 2.22 (1.5 L/min) and N2O (1.5 L/min). Ramosetron (0.3 mg) was administered approximately 15 min before the expected end of operation. After the operation, the patients were transferred to the post-anesthetic care unit (PACU), where a disposable balloon pump for constant infusion of fentanyl (25 μg/h) was started without a loading dose in the IV group. Only normal saline was administered to the TFP group. The TFP and the pump were removed 48 h after the operation.The patients admitted 1 day before surgery, at which time they were randomized into 2 groups using a computer-generated, permuted-block schedule (block size = 4). The assignments were concealed in opaque envelopes and opened immediately before choosing study drugs by a nurse who was blinded to this study and was responsible for preparing the study drugs. Patients in the TFP group received a single TFP  affixed to the anterior chest wall 14 h before surgery. The IV group received a placebo patch. Pre-anesthetic medication was not administered to patients in either group. Laparoscopic cholecystectomy was performed by one surgeon. Anesthesia was induced with 1.5-2.5 mg/kg propofol and 0.8 mg/kg rocuronium. After tracheal intubation, anesthesia was maintained with desflurane-O2.3Fentanyl concentrations were measured in blood taken from the peripheral vein at admission (baseline) and 1, 6, 12, 24, and 48 h postoperatively. Venous blood was centrifuged at 3000 rpm for 10 min, and the plasma was frozen within 30 min at -70°C until used in the assays, which were performed at the end of the study. Fentanyl concentrations were measured using commercially available enzyme-linked immunosorbent assay (ELISA) kits . The detection limit of the assay was 0.02 ng/mL.2.4Adverse effects, including nausea, vomiting, dizziness, itching, and respiratory depression (oxygen saturation < 90%), were monitored continuously from attachment of the TFP or placebo patch to 48 h postoperatively. Respiratory depression was monitored by pulse oximetry. Pain severity at cough was evaluated 1, 6, 24, and 48 h postoperatively. Pain was assessed according to an 11-point numeric rating scale (NRS), which ranged from 0 (no pain) to 10 (most severe pain imaginable). When the NRS score was ≥ 4, 30 mg of IV ketorolac was given in the PACU and 50 mg of tramadol was administered in the ward.2.5t test was performed for continuous normally distributed variables. Fentanyl concentrations at each time point were compared between the 2 groups using a t test or the Mann–Whitney U test. Categorical variables, including incidence of adverse effects, and consumption of rescue analgesics were analyzed using the Chi-square test or Fisher's exact test, as appropriate. The P-values < .05 were considered significant.Sample size was calculated using a power analysis  based on our preliminary study. The mean concentrations of fentanyl 12 h postoperatively were 3.181 ng/mL in the TFP group and 2.719 ng/mL in the IV group. The standard deviation (SD) was 0.510. Thus, 27 patients were required in each group, and 68 patients were recruited to take into account an estimated dropout rate of 20%. The SPSS 24.0  was used for the statistical analysis. Student's 3Sixty-eight patients who underwent laparoscopic cholecystectomy under general anesthesia were allocated to the TFP and IV groups. Three patients in the TFP group were excluded before surgery because they complained of nausea and therefore declined further participation. One patient in the IV group was excluded due to the need for an open cholecystectomy, which was determined intraoperatively. One patient in each group was excluded after surgery due to nausea. Two patients in the IV group were excluded because their data were lost. Thus, 60 patients were included in the final analysis Fig. .P < .01, Fig. Table 4 In a study reported in 1989, the concentration of fentanyl 24 h after applying 75 μg/h TFP was 1.46 ± 0.97 ng/mL. In another study in 1995, fentanyl concentration showed a wide range (0.85–2.95 ng/mL) and respiratory problems developed in 1 patient whose concentration of fentanyl was 1.79 ng/mL.In this study, the peak fentanyl concentration (3.27 ± 0.34 ng/mL) in the TFP group occurred 1 h postoperatively, which was approximately 16 h after the patch had been applied. The concentration was relatively constant from that time until the patch was removed. This time pattern is similar to those in other studies, but the constant concentration was higher than in previous studies. In 1988, Holley and van Steennis reported that the steady-state serum concentration in patients with a 100 μg/h TFP was 2.15 ± 0.93 ng/mL. However, most of the studies measuring fentanyl concentrations were performed too long ago. New researches for the TFP need to be performed with the remarkable laboratory technology.In a study that evaluated the fentanyl concentration using a 100 μg/h transdermal fentanyl delivery system, serum fentanyl concentration increased gradually during the 1st 14 h after attaching the patch, and was relatively constant from 14 to 24 h (1.8 ± 0.8 ng/mL). The previously reported fentanyl concentrations associated with 50% depression of CO2 responsiveness were in the range of 1.5–3.0 ng/mL and hypoventilation occurs in 15% of patients at levels > 1.75 ng/mL. In this study, the peak fentanyl concentration in the IV group was 2.9 ± 0.44 ng/mL 24 h postoperatively, followed by a decrease to 2.0 ± 0.89 ng/mL 48 h postoperatively. Because the aim of this study was comparison of the fentanyl concentration between TFP (25 μg/h) and same dose of IV-constant infusion (25 μg/h), the loading dose was not given in IV- group. The loading dose might be essential for acute postoperative pain control. If more blood samples for fentanyl concentration had been taken between 12 and 24 h postoperatively, it would have been more accurate to compare the plateau state time between the 2 groups.Even with the lower-dose fentanyl patch used in the present study, higher fentanyl concentrations were obtained. However, significant adverse effects such as respiratory depression did not occur. When applied 50 and 75 μg/h TFP 2 h before abdominal hysterectomy, apenic episodes, incidence of slow respiratory rate, and increased requirement for oxygen supplementation were increased between 5 and 36 h after surgery. The fentanyl concentration was various when the patients were withdrawal due to respiratory depression (0.93–2.23 ng/mL). They estimated the minimum effective fentanyl concentration using an IV-PCA set with a basal infusion rate of 20 μg/h and a bolus “demand” dose of 20 μg. The mean minimum effective concentration (MEC) was 0.63 ± 0.25 ng/mL . The MEC in the study by Lehmann et al was 1.35 ± 0.86 ng/mL . In another study, mean plasma fentanyl concentrations were 0.51 ± 0.19, 1.42 ± 0.14, and 1.90 ± 0.3 ng/mL after continuous IV infusion of 25, 100, and 125 μg/h fentanyl, respectively, and the authors proposed that the 100 and 125 μg/h dose rates produced significant analgesic efficacy.This concentration was also higher than previously reported levels and showed a different pattern of change. Gourlay et al reported the fentanyl blood concentration-analgesic response relationship during the treatment of postoperative pain in 1988. However investigations about the efficacy of TFPs for acute postoperative pain management have still been reported.–9 They proposed the efficacy of TFPs by showing a comparison of postoperative pain score, the use of rescue analgesics, and the incidence of adverse effects. Those authors demonstrated that postoperative pain control can be achieved with TFPs at dose rates of 12–50 μg/h without severe adverse effects.,11,13 In present study, though higher fentanyl concentration in TFP group than the IV group, there was no significant difference in pain score and use of rescue analgesics.The TFPs are widely used to control chronic and cancer pain.,16,17 In addition, low-dose TFPs can be effective by providing a background of analgesia, which may be helpful in the management of acute postoperative pain.,18,19 Another advantage is the relatively smooth pharmacokinetic curve of fentanyl concentration. The mean curve of fentanyl concentration is flat over the period after reaching steady state. So, Minville V et al proposed that the TFP is an alternative for postoperative analgesia because it provides constant analgesia without waiting for the pain to increase.The TFPs have several advantages over IV-PCA: they are cheaper, carry a lower risk of infection, have a pre-emptive analgesic effect, and are better tolerated by the patient because they do not require IV access. They also avoid the inconvenience of wearing a bulky PCA pump, which limits patient mobility, particularly during the postoperative period. Moreover, unlike IV-PCA, there is no risk of a program error that could lead to death.,18,20,21 The newly developed patient-controlled ionotrophic transdermal fentanyl delivery system is also expensive.However, some patients suffered severe nausea before surgery and dropped out of this study. It is undesirable that patients suffer adverse effects due to treatment for pain that has not yet occurred. Even removing the patch does not eliminate the symptoms immediately. In addition, delayed onset, large inter-individual variability in pharmacokinetics, and the inability to adjust the dose during the period of application are disadvantages of transdermal patches. However, the chest area is acceptable site for transdermal patch application and blood flow of the skin site has little effect on the systemic drug absorption under normal physiologic condition.,23Thickness and temperature in the skin site of application can alter transdermal fentanyl bioavailability and blood flow to and from the site. Application of a TFP to broken skin can cause to increase of blood fentanyl concentration and skin temperature elevation enhances the absorption of fentanyl.,24,25 Merivirta R et al reported that a patch delivering fentanyl 12 μg/h did not reduce the need for rescue analgesics or pain score for postoperative pain management. Lehmann KA et al also recommended the TFP (75 μg/h) as a basis for postoperative pain relief although additional doses of analgesics were required.The variability in pharmacokinetics, patient-dependent risk factors, and multimodal management of acute postoperative pain must be considered to manage acute postoperative pain effectively.There are some limitations in this study. First, the sample size of this study was limited, so we cannot be assured of the safety of the TFP. Larger sample sizes are needed to confirm the adverse effects of the TFP on postoperative pain management. Second, we used a fixed dose of TFP or continuous fentanyl infusion regardless of patient body weight. This may affect the pain score and the consumption of rescue analgesics. Third, if the measurement for fentanyl concentration had been performed between 12and 24 h postoperatively, the time of reaching steady state of fentanyl concentration in IV-group would have been more accurate and easier to compare the peak concentration time between 2 groups. Forth, we did not follow the fentanyl levels, the postoperative pain scores, or the adverse effects after removing the patches 48 h after surgery. The fentanyl concentration should still be high enough to be monitored 48 h postoperatively. Fifth, we did not consider the blood pressure during the study period. The blood pressure can affect the pharmacokinetics of the TFP. Sixth, when it comes to the efficacy of pain control, the results of this study are unlikely to be applied to all types of surgery.5In summary, the TFP (25 μg/h) affixed 14 h before surgery reached a higher constant concentration than the same dose setting of a constant IV infusion of fentanyl after surgery. Although the concentration of fentanyl was higher than those of previous researches, there was no respiratory depression. But, there was no advantage of reducing pain score and the use of rescue analgesics.Sung Mi Hwang and Jae Jun Lee designed the research, performed experiments, analyzed and interpreted data, and wrote the manuscript. Jisu Jang and Youngsuk Kwon assisted with analyzing data and writing the manuscript. Jisu Jang, Hyunjin Tark and Young Joon Kim performed experiments, and assisted with taking the blood samples. Byoung Yoon Ryu performed the operations.Sung Mi Hwang and Jae Jun Lee and Jisu Jang edited the manuscript.Conceptualization: Sung Mi Hwang, Jae Jun Lee.Data curation: Jisu Jang, Sung Mi Hwang, Youngsuk Kwon, Hyunjin Tark, Young Joon Kim, Jae Jun Lee.Formal analysis: Jisu Jang, Sung Mi Hwang, Youngsuk Kwon, Jae Jun Lee.Investigation: Hyunjin Tark.Methodology: Young Joon Kim, Byoung Yoon Ryu.Writing – original draft: Jisu Jang, Sung Mi Hwang, Youngsuk Kwon, Jae Jun Lee.Writing – review & editing: Sung Mi Hwang, Jae Jun Lee.Sung Mi Hwang orcid: 0000-0001-6035-786X.


Twelve patients with chronic myofascial pain syndrome of the neck and shoulder underwent an injection of Prabotulinumtoxin A. Painful muscles containing trigger points were injected in the mid-belly. Pain scores and quality of life measurements were assessed at baseline, as well as 6 weeks and 12 weeks post-injection. Safety and tolerability were also assessed. This trial is registered under clinical research information service (CRIS) number KCT0001634. Patients injected with Prabotulinumtoxin A showed a significant improvement in pain at 12 weeks (p < 0.001). At 6 weeks, the pain had not significantly improved compared with baseline (p = 0.063). However, at that time, 41.7% of patients were characterized as Prabotulinumtoxin A responders, with a 30% reduction in pain rating score compared to baseline. In the Neck Disability Index scores, the patients demonstrated significant improvement at both 6 weeks and 12 weeks. No serious adverse effects occurred during the study. Prabotulinumtoxin A injection into chronically painful muscles associated with cervical and shoulder girdle myofascial pain syndrome resulted in an improvement in pain scores and quality of life lasting at least 12 weeks. Additionally, the injections were well tolerated. As these are preliminary findings in a pilot study, future studies should carefully consider using randomized, controlled, prospective trials.Myofascial pain syndrome is a common painful condition encountered in the general population. Previous studies evaluating the efficacy of botulinum toxin for the treatment of myofascial pain syndrome are limited, with variable results. This prospective study investigated the efficacy and safety of direct injection of Prabotulinumtoxin A (Nabota Myofascial pain syndrome is a chronic pain syndrome caused by myofascial trigger points, most commonly those of the neck and shoulder. Treatments for myofascial pain syndrome include pharmacotherapy, physical therapy, therapeutic exercise, and trigger point injections .Trigger point injections are treatments that directly target myofascial trigger points using local anesthetics. They are typically performed several times per week. However, botulinum toxin can be administered in a single injection that lasts for many months ,3,4.Zhou et al.  describe® is a botulinum toxin type A protein of high purity and quality developed by Daewoong Pharmaceutical in Korea, from the natural strain Clostridium botulinum (type A). Clinical trials have been conducted to demonstrate its effects on skin wrinkles and upper limb spasticity in stroke patients [Nabotapatients ,7.®) injection in patients with cervical and shoulder girdle myofascial pain syndrome.The purpose of the present study was to confirm the efficacy and safety of Prabotulinumtoxin A . However, there was no statistically significant difference either post-injection (p = 0.88) or after 6 weeks compared (p = 0.06) to baseline. The pain rating scale values were 5.1 ± 0.3, 4.8 ± 0.4, 4.2 ± 1.2 and 2.6 ± 1.3 at baseline, post-injection, 6 weeks, and 12 weeks, respectively  and 12 weeks (p = 0.001) compared to baseline. However, there was no statistically significant difference post-injection (p = 0.37) compared to baseline. The Neck Disability Index values were 32.1 ± 11.9, 33.3 ± 32.3, 23.4 ± 14.7, and 17.8 ± 13.6 at baseline, post-injection, 6 weeks, and 12 weeks, respectively  in patients with cervical and shoulder girdle myofascial pain syndrome. A previous study [® injection in patients with cervical and shoulder girdle myofascial pain syndrome significant decreased both pain scale and Neck Disability Index scores. There were no adverse events related to vital signs, physical and neurological examinations, and laboratory tests.This study evaluated the efficacy and safety of Prabotulinumtoxin A , a new botulinum toxin A originating from wild-type Clostridium botulinum A, presents higher purity of botulinum toxin A, which is confirmed by size exclusion high-performance liquid chromatography analysis [®) injection into painful muscle groups for myofascial pain.Prabotulinumtoxin A  under number (KCT0001634), approved on 23 September 2015. Twelve patients were enrolled in this prospective study, all of whom agreed in writing to voluntarily participate in the clinical trial and met the screening criteria. The inclusion criteria were as follows: (1) Male or female subjects no younger than 20 years; (2) myofascial pain of the neck and shoulders of at least 3-months duration; (3) failed standard therapy ; (4) pain scale score of 5 or higher, and (5) voluntary informed consent signed by the patient after the objectives and methods of the clinical study had been explained. The exclusion criteria were as follows: (1) Patients with a history of neuromuscular disease; (2) patients receiving botulinum toxin A therapy within the past 4 months; (3) patients with a known allergy or sensitivity to any component of the test medication; (4) subjects who were pregnant or breastfeeding; (5) patients with significant atrophy of the muscles in the target injection area; (6) patients with muscle weakness in the target area ; (7) subjects deemed inappropriate for entry into this study in the judgement of the investigator; (8) patients taking muscle-relaxant drugs within 4 weeks prior to the screening visit; (9) patients taking aspirin, nonsteroidal anti-inflammatory drugs or antiplatelet drugs; (10) patients with another active illness; (11) patients with a moderate degree of cardiac disease or pulmonary disease; (12) patients with a herniated cervical nucleus pulposus, a straight cervical spine or a cervical sprain, and (13) patients who had participated in an investigational drug study or bioequivalence study within 3 months prior to the screening visit.This study was conducted with the approval by the Catholic University of Korea, Incheon St. Mary’s Hospital Institutional Research Review Board (IRB No. OC14MISI0102). This clinical trial was registered with the Clinical Research Information Service  was diluted with 4 mL of saline. The painful muscle containing the trigger point was injected with up to 50 Units of Nabota®, and a maximum of 200 Units was allowed for each patient. The target muscle and dose for each injection were selected by a single skilled physician. The injection sites and doses for each muscle are shown in For the injections, one vial of NabotaAll patients received follow-up visits at 6 and 12 weeks after the injection. At each visit, the safety and efficacy of the drug were evaluated through a physical examination as well as a numerical rating scale for pain and a Neck Disability Index. The primary outcome measure was the percentage of patients whose pain scores  improved by 30% or more at 6 and 12 weeks after the injection compared to baseline. Disability as a secondary outcome was quantified using the Neck Disability Index.® software, version 9.3 . Paired T-test or Wilcoxon signed-rank test were used to evaluate differences in the pain scale and Neck Disability Index. A p-value < 0.05 was considered statistically significant.Statistical analyses were performed using SAS


Sometim problem ), and in problem , 4 and s problem .It is estimated that over 95% of cases of orofacial pain result from dental causes . After dental pain, the second most common cause of orofacial pain is TMJ disorders  and with < 60-year-old subjects (n=29). The orofacial pain in older patients declined significantly at 1-month after treatment, as did that of younger patients. Also, some transient side effects are described, of mild entity, and the strategies to manage them, resolving the cases within 3 weeks.The efficacy and safety of botulinum toxin type A in treating adult patients with idiopathic trigeminal neuralgia are described in this special issue by Liu et al., who applied the protocol in a group of ≥ 80-year-old subjects (In the field of neurosurgery, E.‐S. Allam et al. report an updated review on the ultrasound-guided intervention for the treatment of trigeminal neuralgia. The strategic importance of this technique is due to the fact that ultrasound provides real‐time images of the muscles and accompanying arteries and can be used to guide the needle to the target region. Most importantly, ultrasound guidance significantly reduces the risk of collateral injury to vital neurovascular structures. The authors also describe the regional anatomy and ultrasound‐guided injection and techniques for the trigeminal nerve and its branches, including the supraorbital, supratrochlear, infraorbital, mental, auriculotemporal, maxillary, and mandibular nerves.Moreover, in the field of maxillofacial surgery, the orofacial pain complainants in a group of 286 subjects already treated with orthognathic surgery are described in this special issue by Agbaje et al. They conclude that, in the posttreatment period after maxillofacial surgery, TMJ symptoms do develop both in patients with and without a previous history of TMJ complaints, and most of these patients can be managed with nonsurgical therapeutic modalities.In conclusion, it is expected this special issue to address and report recent advanced topics in the management of orofacial pain and describe the ultimate new techniques and tools both from an academic and real-world applications point of view. Current views included in this issue will hopefully allow us to assess a perspective of the orofacial pain and to develop and familiarize with new research studies related to the most recent multidisciplinary viewpoints.