Resting-state brain activity as a biomarker of chronic pain impairment and a mediator of its association with pain resilience.

Past cross-sectional chronic pain studies have revealed aberrant resting-state brain activity in regions involved in pain processing and affect regulation. However, there is a paucity of longitudinal research examining links of resting-state activity and pain resilience with changes in chronic pain outcomes over time. In this prospective study, we assessed the status of baseline (T1) resting-state brain activity as a biomarker of later impairment from chronic pain and a mediator of the relation between pain resilience and impairment at follow-up. One hundred forty-two adults with chronic musculoskeletal pain completed a T1 assessment comprising a resting-state functional magnetic resonance imaging scan based on regional homogeneity (ReHo) and self-report measures of demographics, pain characteristics, psychological status, pain resilience, pain severity, and pain impairment. Subsequently, pain impairment was reassessed at a 6-month follow-up (T2). Hierarchical multiple regression and mediation analyses assessed relations of T1 ReHo and pain resilience scores with changes in pain impairment. Higher T1 ReHo values in the right caudate nucleus were associated with increased pain impairment at T2, after controlling for all other statistically significant self-report measures. ReHo also partially mediated associations of T1 pain resilience dimensions with T2 pain impairment. T1 right caudate nucleus ReHo emerged as a possible biomarker of later impairment from chronic musculoskeletal pain and a neural mechanism that may help to explain why pain resilience is related to lower levels of later chronic pain impairment. Findings provide empirical foundations for prospective extensions that assess the status of ReHo activity and self-reported pain resilience as markers for later impairment from chronic pain and targets for interventions to reduce impairment. PRACTITIONER POINTS: Resting-state markers of impairment: Higher baseline (T1) regional homogeneity (ReHo) values, localized in the right caudate nucleus, were associated with exacerbations in impairment from chronic musculoskeletal pain at a 6-month follow-up, independent of T1 demographics, pain experiences, and psychological factors. Mediating role of ReHo values: ReHo values in the right caudate nucleus also mediated the relationship between baseline pain resilience levels and later pain impairment among participants. Therapeutic implications: Findings provide empirical foundations for research extensions that evaluate (1) the use of resting-state activity in assessment to identify people at risk for later impairment from pain and (2) changes in resting-state activity as biomarkers for the efficacy of treatments designed to improve resilience and reduce impairment among those in need.

Association between multisite musculoskeletal pain and disability trajectories among community-dwelling older adults.

BACKGROUND: Pain is linked to disability, but how multisite musculoskeletal pain leads to disability over time is not well elaborated. OBJECTIVE: To examine the associations of multisite musculoskeletal pain with disability among a nationally representative cohort. DESIGN: We used data from the National Health and Aging Trends Study (NHATS) 2015-22. Disability was assessed by basic activities of daily living (ADL) and instrumental activities of daily living (IADL). PARTICIPANTS: A total of 5557 individuals with multisite musculoskeletal pain dwelling in the community were included in this study. METHODS: Group-based trajectory models were applied to identify distinct profiles of disability in ADL and IADL. Design-based logistic regressions were used to examine associations among multisite musculoskeletal pain, disability, and dual trajectory group memberships, adjusted for sociodemographic, health status, behavioral, and mental characteristics. RESULTS: Persons who experienced multisite musculoskeletal pain were at higher risk of disability in ADL and IADL. We identified five heterogeneous disability trajectories and named them based on baseline levels and rates of increase over time. Approximately, 52.42% of older adults with multisite musculoskeletal pain were in trajectories with ADL and IADL declines, and 33.60% experienced a rapid decline. Multisite musculoskeletal pain was associated with elevated relative risk for the adverse disability trajectories, which generally increases with multisite musculoskeletal pain frequency and number of sites. CONCLUSIONS: Persons with multisite musculoskeletal pain had a higher risk of disability. It is essential to adopt effective pain management strategies to maintain the independent living ability of older adults and to realize active aging.

Physical activity based on daily steps in patients with chronic musculoskeletal pain: evolution and associated factors.

BACKGROUND: People with chronic musculoskeletal pain (CMSP) often have low physical activity. Various factors can influence the activity level. The aim of this study was to monitor physical activity, assessed by the number of steps per day, over time in people with CMSP and identify factors that could be associated with this activity feature. METHODS: This prospective study involved people undergoing rehabilitation following an orthopedic trauma that had led to CMSP. At entry, participants completed self-reported questionnaires assessing pain, anxiety, depression, catastrophyzing, kinesiophobia, and behavioural activity patterns (avoidance, pacing and overdoing). They also underwent functional tests, assessing walking endurance and physical fitness. To determine daily step counts, participants wore an accelerometer for 1 week during rehabilitation and 3 months post-rehabilitation. The number of steps per day was compared among three time points: weekend of rehabilitation (an estimate of pre-rehabilitation activity; T1), weekdays of rehabilitation (T2), and post-rehabilitation (T3). Linear regression models were used to analyze the association between daily steps at T2 and at T3 and self-reported and performance-based parameters. RESULTS: Data from 145 participants were analyzed. The mean number of steps was significantly higher during T2 than T1 and T3 (7323 [3047] vs. 4782 [2689], p < 0.001, Cohen's d = 0.769, and 4757 [2680], p < 0.001, Cohen's d = 0.693), whereas T1 and T3 results were similar (p = 0.92, Cohen's d = 0.008). Correlations of number of steps per day among time points were low (r ≤ 0.4). Multivariable regression models revealed an association between daily steps at T2 and pain interfering with walking, anxiety and overdoing behaviour. Daily steps at T3 were associated with overdoing behaviour and physical fitness. CONCLUSIONS: Despite chronic pain, people in rehabilitation after an orthopedic trauma increased their physical activity if they were given incentives to do so. When these incentives disappeared, most people returned to their previous activity levels. A multimodal follow-up approach could include both therapeutic and environmental incentives to help maintain physical activity in this population.

Impact of Musculoskeletal Pain on Functioning and Disability in Children with Juvenile Idiopathic Arthritis in Iceland.

AIMS: 1) to map questions of pain from a survey to the International Classification of Functioning, Disability and Health (ICF) 2) to compare the impact of musculoskeletal pain on functioning based on the different components of the ICF in children with juvenile idiopathic arthritis (JIA) and age-matched peers. METHOD: A cross-sectional case-control survey. A total of 28 children with JIA and 36 age-matched children participated. The survey included questions on the child's sex and age, about pain experienced, number of painful body areas, pain frequency and three short forms of Patient-Reported Outcome Measurement Information System (PROMIS) pain questionnaires. Sixteen children with JIA (57%) and 10 peers (28%) reported pain during past seven days. Their responses were used in the description of impact of pain. RESULTS: After the mapping of the questions to ICF, a comparison between the two groups indicated that a higher number of children with JIA described effects of pain on mental function, mobility, general tasks and demands, than their peers. More children with JIA expressed to others that they had pain, non-verbally and verbally. CONCLUSION: The findings provide important information about the impacts of pain on daily life in children with JIA and about their intervention needs.

[THE MUSCULAR COMPONENT OF FIBROMYALGIA PATHOPHYSIOLOGY].

INTRODUCTION: Fibromyalgia syndrome (FMS) is a chronic pain syndrome, prevalent in women more than men. The main symptoms are widespread musculoskeletal pain, fatigue, and weakness. To date, the pathophysiological mechanisms are unclear, and there are several pathogenic theories elucidating this condition. In this review, we summarized articles published in the past few years, regarding the effect of musculoskeletal dysfunction on FMS. We focused on the musculoskeletal system and central nervous system (CNS) disarrays.

The Portuguese version of the musculoskeletal pain intensity and interference questionnaire for musicians (MPIIQM-Pt): Translation, cultural adaptation, and multicenter validation study in professional orchestra musicians.

OBJECTIVES: We aim to assess the validity and reliability of the Musculoskeletal Pain Intensity and Interference Questionnaire for Musicians (MPIIQM) and to add to its cross-cultural adaptation process by translating, culturally adapting, and validating the MPIIQM into European Portuguese language in the population of Portuguese musicians. METHODS: A Portuguese version of the MPIIQM (MPIIQM-Pt) was created through a process of forward and back translation, pilot testing, and cultural adaptation by expert panel evaluation. The psychometric evaluation was performed in a validation sample of 134 musicians, at baseline and after 7 days. RESULTS: The high degree of internal consistency and the substantial test-retest reliability coefficients were demonstrated for each subscale (α = 0.896 and ICC = 0.997 for "pain intensity," and α = 0.879 and ICC = 0.999 for "pain interference," respectively). Exploratory factor analysis indicated two-factor structure (pain intensity and interference) that explained 75.5% of the variance. Both convergent and divergent validity are well demonstrated, confirming more than 90% of the previously defined hypotheses regarding correlations with other measures. DISCUSSION: MPIIQM-Pt is the first validated questionnaire to evaluate pain among Portuguese musicians. It showed excellent psychometric properties, both in terms of internal consistency, test-retest reliability, factor analysis, and construct validity. Therefore, it is a valid and reliable tool suitable for both research and clinical practice purposes. MPIIQM-Pt will allow the development of more robust studies on pain among musicians and the improved assessment and monitoring of pain in this population, filling an important gap in this field of Pain Medicine.

The effect of elevated muscle pain on neuromuscular fatigue during exercise.

PURPOSE: Muscle pain can impair exercise performance but the mechanisms for this are unknown. This study examined the effects of muscle pain on neuromuscular fatigue during an endurance task. METHODS: On separate visits, twelve participants completed an isometric time-to-task failure (TTF) exercise of the right knee extensors at ~ 20% of maximum force following an intramuscular injection of isotonic saline (CTRL) or hypertonic saline (HYP) into the vastus lateralis. Measures of neuromuscular fatigue were taken before, during and after the TTF using transcranial magnetic stimulation (TMS) and peripheral nerve stimulation. RESULTS: The mean pain intensity was 57 ± 10 in HYP compared to 38 ± 18 in CTRL (P < 0.001). TTF was reduced in HYP (4.36 ± 0.88 min) compared to CTRL (5.20 ± 0.39 min) (P = 0.003). Maximum voluntary force was 12% lower at minute 1 (P = 0.003) and 11% lower at minute 2 in HYP (P = 0.013) compared to CTRL. Voluntary activation was 4% lower at minute 1 in HYP compared to CTRL (P = 0.006) but not at any other time point (all P > 0.05). The TMS silent period was 9% longer at 100 s during the TTF in HYP compared to CTRL (P = 0.026). CONCLUSION: Muscle pain reduces exercise performance through the excacerbation of neuromuscular fatigue that is central in origin. This appears to be from inhibitory feedback from group III/IV nociceptors which acts to reduce central motor output.

Are There Distinct Statistical Groupings of Mental Health Factors and Pathophysiology Severity Among People with Hip and Knee Osteoarthritis Presenting for Specialty Care?

BACKGROUND: There is mounting evidence that objective measures of pathophysiology do not correlate well with symptom intensity. A growing line of inquiry identifies statistical combinations (so-called "phenotypes") of various levels of distress and unhelpful thoughts that are associated with distinct levels of symptom intensity and magnitude of incapability. As a next step, it would be helpful to understand how distress and unhelpful thoughts interact with objective measures of pathologic conditions such as the radiologic severity of osteoarthritis. The ability to identify phenotypes of these factors that are associated with distinct levels of illness could contribute to improved personalized musculoskeletal care in a comprehensive, patient-centered model. QUESTIONS/PURPOSES: (1) When measures of mental health are paired with radiologic osteoarthritis severity, are there distinct phenotypes among adult patients with hip and knee osteoarthritis? (2) Is there a difference in the degree of capability and pain self-efficacy among the identified mental health and radiologic phenotypes? (3) When capability (Patient-reported Outcomes Measurement Information System Physical Function [PROMIS PF]) is paired with radiographic osteoarthritis severity, are there distinct phenotypes among patients with hip and knee osteoarthritis? (4) Is there a difference in mental health among patients with the identified capability and radiologic phenotypes? METHODS: We performed a secondary analysis of data from a study of 119 patients who presented for musculoskeletal specialty care for hip or knee osteoarthritis. Sixty-seven percent (80 of 119) of patients were women, with a mean age of 62 ± 10 years. Seventy-six percent (91 of 119) of patients had knee osteoarthritis, and 59% (70 of 119) had an advanced radiographic grade of osteoarthritis (Kellgren-Lawrence grade 3 or higher). This dataset is well-suited for our current experiment because the initial study had broad enrollment criteria, making these data applicable to a diverse population and because patients had sufficient variability in radiographic severity of osteoarthritis. All new and returning patients were screened for eligibility. We do not record the percentage of eligible patients who do not participate in cross-sectional surveys, but the rate is typically high (more than 80%). One hundred forty-eight eligible patients started the questionnaires, and 20% (29 of 148) of patients did not complete at least 60% of the questionnaires and were excluded, leaving 119 patients available for analysis. We measured psychologic distress (Patient Health Questionnaire-2 [PHQ-2] and Generalized Anxiety Disorder-2 questionnaire [GAD-2]), unhelpful thoughts about pain (Pain Catastrophizing Scale-4 [PCS-4]), self-efficacy when in pain (Pain Self-Efficacy Questionnaire-2), and capability (PROMIS PF). One of two arthroplasty fellowship-trained surgeons assigned the Kellgren-Lawrence grade of osteoarthritis based on radiographs in the original study. We used a cluster analysis to generate two sets of phenotypes: (1) measures of mental health (PHQ-2, GAD-2, PCS-4) paired with the Kellgren-Lawrence grade and (2) capability (PROMIS PF) paired with the Kellgren-Lawrence grade. We used one-way ANOVA and Kruskal-Wallis H tests to assess differences in capability and self-efficacy and mental health, respectively. RESULTS: When pairing measures of psychologic distress (PHQ-2 and GAD-2) and unhelpful thoughts (catastrophic thinking) with the grade of radiographic osteoarthritis, six distinct phenotypes arose. These groups differed in terms of capability and pain self-efficacy (for example, mild pathology/low distress versus average pathology/high distress [PROMIS PF, mean ± standard deviation]: 43 ± 6.3 versus 33 ± 4.8; p = 0.003). When pairing the degree of capability (PROMIS PF) with the Kellgren-Lawrence grade, four distinct phenotypes arose. Patients in three of these did not differ in terms of disease severity but had notable variation in the degree of limitations. Patients with these radiologic and capability phenotypes differed in terms of distress and unhelpful thoughts (for example, moderate pathology/low capability versus mild pathology/high capability [PHQ-2, median and interquartile range]: 3 [1 to 5] versus 0 [0 to 0]; p < 0.001). CONCLUSION: Statistical groupings ("phenotypes") that include both measures of pathology and mental health are associated with differences in symptom intensity and magnitude of incapability and have the potential to help musculoskeletal specialists discern mental and social health priorities. Future investigations may test whether illness phenotype-specific comprehensive biopsychosocial treatment strategies are more effective than treatment of pathology alone. LEVEL OF EVIDENCE: Level III, prognostic study.

Radiographic Severity May Not be Associated with Pain and Function in Glenohumeral Arthritis.

BACKGROUND: Despite the routine use of plain radiographs to stratify the severity of glenohumeral osteoarthritis, little is known about the relationship between radiographic measures and patient-perceived pain and function. QUESTIONS/PURPOSES: (1) What radiographic findings are associated with worse pain and function in patients with glenohumeral osteoarthritis? (2) What demographic factors are associated with worse pain and function in patients with glenohumeral osteoarthritis? METHODS: This retrospective study included patients presenting for an initial office visit for primary glenohumeral osteoarthritis. Patients with other concurrent shoulder pathologic findings, prior surgery, lack of pain and functional scores, recent injection, or inadequate radiographs were excluded. Between January 2017 and January 2019, 3133 patients were eligible based on these inclusion criteria; 59% (1860) had outcome assessments and 48% (893) of those had radiographs. An additional 42% (378) of those with radiographs were excluded because of other shoulder findings, recent injection, prior surgery, or inadequate radiographs, leaving 16% (515 of 3133) who were fully analyzed in this study. A radiographic review included the joint space width, posterior humeral head subluxation, inferior humeral head osteophyte size, cystic change, and head asphericity. Additionally, radiographic arthritis was classified according to the Walch, Samilson-Prieto, and Kellgren-Lawrence classifications by two separate reviewers. Radiographic and demographic criteria as well as the presence of psychologic or mental illness were correlated with VAS Pain (range 1-10; minimal clinically important difference [MCID] 1.6), American Shoulder and Elbow Surgeons (ASES; range 0-100; MCID 13.6), Single Assessment Numeric Evaluation (SANE; range 0-100; MCID 14), and Simple Shoulder Test (SST; range 0-12; MCID 1.5) scores using univariate and multivariable regression analyses. RESULTS: After accounting for age, gender, and psychologic illness in the multivariable analysis, we found that patients with Samilson-Prieto Grade 4 arthrosis had lower VAS Pain scores (ß = -1.9; p = 0.02) than those with Grade 0 or 1 did; however, no clinically important associations were found between Samilson-Prieto Grade 4 and ASES (ß = 7; p = 0.25), SANE (ß = 4; p = 0.63), or SST (ß = 0.5; p = 0.62) scores. No clinically important associations were found between Kellgren-Lawrence Grade 3 and VAS Pain (ß = 1.4; p = 0.10), ASES (ß = -8; p = 0.22), SANE (ß = -13; p = 0.11), or SST scores (ß = 0.4; p = 0.66). Radiographic joint space and posterior subluxation also did not have any clinically important associations with VAS Pain or functional scores. In assessing Walch glenoid type, there was no clinically important association between glenoid type and VAS Pain (F = 3.1; p < 0.01), ASES (F = 1.9; p = 0.15), SANE (F = 0.45; p = 0.66), or SST scores (F = 0.76; p = 0.71). Men had higher SST scores than women did (ß = 2.0; p < 0.01), but there were no clinically important differences in VAS Pain (ß = -0.4; p = 0.04), ASES (ß = 6; p < 0.01), or SANE (ß = 4; p = 0.07) scores. No clinically important association was found between age or the presence of any psychologic illness and VAS Pain or functional scores. CONCLUSION: In patients with glenohumeral arthritis, no consistent clinically important differences in pain or function were discovered with respect to radiographic or demographic factors. Surgeons should understand that the pain levels of patients with glenohumeral arthritis may not parallel radiographic severity. Future studies can build on these findings by examining other non-radiographic or demographic factors that affect pain in patients with shoulder arthritis, such as psychological factors. LEVEL OF EVIDENCE: Level III, prognostic study.

Genome-wide association study identifies RNF123 locus as associated with chronic widespread musculoskeletal pain.

BACKGROUND AND OBJECTIVES: Chronic widespread musculoskeletal pain (CWP) is a symptom of fibromyalgia and a complex trait with poorly understood pathogenesis. CWP is heritable (48%-54%), but its genetic architecture is unknown and candidate gene studies have produced inconsistent results. We conducted a genome-wide association study to get insight into the genetic background of CWP. METHODS: Northern Europeans from UK Biobank comprising 6914 cases reporting pain all over the body lasting >3 months and 242 929 controls were studied. Replication of three independent genome-wide significant single nucleotide polymorphisms was attempted in six independent European cohorts (n=43 080; cases=14 177). Genetic correlations with risk factors, tissue specificity and colocalisation were examined. RESULTS: Three genome-wide significant loci were identified (rs1491985, rs10490825, rs165599) residing within the genes Ring Finger Protein 123 (RNF123), ATPase secretory pathway Ca2+transporting 1 (ATP2C1) and catechol-O-methyltransferase (COMT). The RNF123 locus was replicated (meta-analysis p=0.0002), the ATP2C1 locus showed suggestive association (p=0.0227) and the COMT locus was not replicated. Partial genetic correlation between CWP and depressive symptoms, body mass index, age of first birth and years of schooling were identified. Tissue specificity and colocalisation analysis highlight the relevance of skeletal muscle in CWP. CONCLUSIONS: We report a novel association of RNF123 locus and a suggestive association of ATP2C1 locus with CWP. Both loci are consistent with a role of calcium regulation in CWP. The association with COMT, one of the most studied genes in chronic pain field, was not confirmed in the replication analysis.

Physical pain and musculoskeletal discomfort in vascular surgeons.

OBJECTIVE: Work-related pain and disability have been reported in the literature among surgeons. This national survey was designed to identify the prevalence and severity of these symptoms in vascular surgeons. METHODS: A survey was emailed to the 2910 members of the Society for Vascular Surgery. Physical pain was evaluated based on body part, and type of vascular procedure performed using the Borg 0 to 10 pain scale. Wellness questions were also queried. RESULTS: A total of 775 of Society for Vascular Surgery members responded, with a 26.6% response rate. Retirees were excluded from the study (n = 39). Among those actively working (n = 736), surgeons have been practicing surgery, on average, for 17.2 ± 11.6 years, with a mean age of 51.4 ± 10.9 years, and 83.6% are male. After a full day of open surgery, the majority of the responding vascular surgeons are in a moderately strong amount of pain (mean score, 4.4 ± 2.3). After a full day of endovascular procedures, most vascular surgeons are in a moderately strong amount of pain (mean score, 3.9 ± 2.4). Pain after open surgery is greatest in the neck, and after endovascular surgery pain is highest in the lower back. Surgeons performing endovenous procedures demonstrated the lowest pain scores (2.0 ± 2.0). In total, 36.9% (242/655, 81 missing responses) have sought medical care for work-related pain, with 8.3% (61/736) taking time away from the operating room. Of those, 26.2% (193/736) report pain severe enough that it interferes with sleep. Seventy-two (10%) required surgery or other significant medical procedures. Of the 39 retirees, 26% ended their careers owing to physical disabilities from work-related pain. Out of the entire cohort, 52.7% (334/633,103 missing responses) feel that physical discomfort will affect the longevity of their careers. Additionally, we found that high work-related physical discomfort is significantly associated with burnout (burnout vs no burnout; P < .0001). CONCLUSIONS: Our study shows that the majority of practicing vascular surgeons responding to the survey are in pain after a day of operating. Addressing work-related pain serves to improve the lives and careers of vascular surgeons and enhance surgical longevity.

Reduced specific force in patients with mild and severe facioscapulohumeral muscular dystrophy.

BACKGROUND: Specific force, that is the amount of force generated per unit of muscle tissue, is reduced in patients with facioscapulohumeral muscular dystrophy (FSHD). The causes of reduced specific force and its relation with FSHD disease severity are unknown. METHODS: Quantitative muscle magnetic resonance imaging (MRI), measurement of voluntary maximum force generation and quadriceps force-frequency relationship, and vastus lateralis muscle biopsies were performed in 12 genetically confirmed patients with FSHD and 12 controls. RESULTS: Specific force was reduced by ~33% in all FSHD patients independent of disease severity. Quadriceps force-frequency relationship shifted to the right in severe FSHD compared to controls. Fiber type distribution in vastus lateralis muscle biopsies did not differ between groups. CONCLUSIONS: Reduced quadriceps specific force is present in all FSHD patients regardless of disease severity or fatty infiltration. Early myopathic changes, including fibrosis, and non-muscle factors, such as physical fatigue and musculoskeletal pain, may contribute to reduced specific force.

Comparative efficacy of therapeutics for traumatic musculoskeletal pain in the emergency setting: A network meta-analysis.

OBJECTIVE: Musculoskeletal pain control is essential in the management of trauma patients in the emergency department (ED). Here, we performed a network meta-analysis of the use of analgesics to manage traumatic musculoskeletal pain. METHOD: This network meta-analysis (NMA) protocol was registered in PROSPERO (CRD42020150145). Electronic databases were searched for randomized controlled trials comparing systemic pharmaceutical interventions for treating traumatic musculoskeletal pain in the ED setting. The outcomes were global efficacy and changes in pain intensity. RESULTS: Eighteen studies (2656 patients, four medication classes) met the inclusion criteria. The top-ranking medication class for global efficacy was nonsteroidal anti-inflammatory drugs (NSAIDs; network odds ratio: 0.52, 95% credible interval: 0.34-0.81, surface under the cumulative ranking curve score: 86). No interventions were more effective at decreasing pain intensity than opioids at 60 min. CONCLUSION: NSAIDs were the most effective medications for treating traumatic musculoskeletal pain, and combination therapies may not have advantages in the ED setting.

Pain in neurodegenerative diseases with atypical parkinsonism: a systematic review on prevalence, clinical presentation, and findings from experimental studies.

Parkinson's disease-related pain has increasingly been investigated in research studies. Still, only a few studies have addressed the prevalence and clinical characteristics of pain in neurodegenerative disorders with atypical parkinsonism. The existing evidence, although scarce, suggests that, similarly as in Parkinson's disease, individuals with neurodegenerative diseases with atypical parkinsonism might be predisposed to the development of persistent pain. Today, as the global population is aging and we face an epidemic of neurodegenerative disorders, under-treated pain is taking a great toll on an ever-rising number of people. Here, we provide an up-to-date review of the current knowledge on the prevalence of pain, its clinical features, and findings from experimental studies that might signpost altered pain processing in the most prevalent neurodegenerative disorders with atypical parkinsonism: multiple system atrophy, progressive supranuclear palsy, corticobasal syndrome, frontotemporal dementia, and dementia with Lewy bodies. Finally, we point out the current gaps and unmet needs that future research studies should focus on. Large-scale, high-quality clinical trials, coupled with pre-clinical research, are urgently needed to reveal the exact pathophysiological mechanisms underpinning heightened pain and pave the path for mechanistically-driven analgesic interventions to be developed, ultimately leading to an improvement in the quality of life of individuals with neurodegenerative disorders.

Lower Extremity Pain and Pitching Kinematics and Kinetics in Collegiate Softball Pitchers.

The primary aims of the study were (1) to examine kinematics and kinetics of those pitching with and without lower extremity pain in collegiate softball pitchers, and (2) to determine if there was an association between the lower extremity pain and lower extremity kinematics, trunk kinematics, and shoulder kinetics in collegiate softball pitchers. Thirty-seven NCAA Division I female collegiate softball pitchers (19.8±1.3 yrs,173.7±7.7 cm, 79.0±12.4 kg) participated. Participants were divided into two groups, those who were currently experiencing lower extremity pain and those who were not. Participants threw three rise ball pitches. Kinematic data were collected at 100 Hz using an electromagnetic tracking system. Mann-Whitney U tests revealed no significant kinematic or kinetic differences between pitchers with and without lower extremity pain. Additionally, there were no significant correlations between pain and recorded kinematic and kinetic variables. Considering there were no biomechanical differences observed between pitchers, coaches and athletic trainers should take caution with athlete assessment since athletes may not display altered biomechanics. Further examination into the duration and degree of pain is needed in an attempt to fully understand the implication of pain and pitching mechanics.

Initial Presentation of Pain in Patients with Fibromyalgia.

BACKGROUND: Fibromyalgia is characterized by diffuse musculoskeletal pain at the time of diagnosis, but many patients report their initial symptoms as being focal or local. OBJECTIVES: To evaluate, prospectively, the initial location of body pain in recently diagnosed patients with fibromyalgia. METHODS: Non-selected patients from the rheumatology clinic who were recently diagnosed with fibromyalgia (≤ 2 years) with symptoms of ≤ 4 years participated in our study. Demographic and clinical parameters were documented, as was the initial location of pain they had experienced. Sub-analysis of data according to gender and ethnicity was conducted using chi-squire test. RESULTS: The study comprised 155 patients. Mean age was 39.8 ± 11.7 years; 85% were female. Mean duration of symptoms was 2.11 years and of diagnosis was 0.78 years. Six patients (3.9%) reported initial symptoms of pain as being diffuse from the start, 10 (6.5%) could not remember the location of their initial symptoms, and 139 (90%) reported initial focal pain. Hands were reported as the initial area of pain for 25.2% of the patients, 19.4% reported the back, and 11% reported both trapezial areas as the initial area of pain. In 90% of the patients (excluding patients with back, abdominal, or chest pain) the initial symptoms were bilateral and symmetrical. No significant difference in initial presentation was found among different gender or ethnic groups. CONCLUSIONS: Pain in fibromyalgia patients usually presents as focal and symmetrical. Bilateral hand pain, followed by back pain, was the most common reported area of initial pain among fibromyalgia patients.

The development and use of an anatomy-based retraining program (MusAARP) to assess and treat focal hand dystonia in musicians-A pilot study.

BACKGROUND: Movement dysfunctions are commonly reported in musicians, and in extreme cases may result in a persisting loss of motor control. This condition, whereby motor control of the hand during previously highly trained movements on the instrument is lost, is termed focal hand dystonia. It is widely considered to be a consequence of prolonged repetitive daily practice, often in combination with exposure to a range of other risk factors. Current literature recommends retraining as a promising treatment intervention, although only scant scientific evidence exists on which components should be included in a retraining program, and how these may be best administered. METHODS: A progressive muscle activation and movement exercise program was devised by one of the authors applying a series of anatomy-based off-instrument movement tasks. This series of fine motor control exercises, was used to both assess and retrain focal hand dystonia in a population of musicians. The standardized approach aimed to provide a systematic method of retraining musically relevant muscular synergies that could later be applied to the instrument, while still allowing individual modifications. Retraining sessions were mostly run online as a consequence of the coronavirus pandemic, although some early sessions were also able to be undertaken face to face. Both qualitative and quantitative measures were used in this case series to evaluate program efficacy, due to the typical heterogeneity of the focal hand dystonia participants. This included: blinded external neurological evaluation of video footage using the Tubiana grading system, written subjective feedback, exercise progressions, and performance outcomes. RESULTS: Pilot testing of 4 patients indicated the utility of the program over approximately a 12- month time period. All subjects improved, 2 of whom have returned to pre-dystonia performance levels. These patients reported the importance of patience and persistence with daily exercise sessions in their recovery. CONCLUSION: Using off-instrument playing-relevant exercises to enhance fine motor control and muscle activation can be effective in retraining focal hand dystonia, regardless of additional treatments or level of performance. They should be regularly practiced and progressed in order for effects to be best progressed to instrumental applications. Further research may elucidate whether there are optimal outcomes with single or particular combinations of treatment approaches.

Elevated free secretory component in early rheumatoid arthritis and prior to arthritis development in patients at increased risk.

OBJECTIVES: Considering growing evidence of mucosal involvement in RA induction, this study investigated circulating free secretory component (SC) in patients with either recent-onset RA or with ACPA and musculoskeletal pain. METHODS: Two prospective cohorts were studied: TIRA-2 comprising 452 recent-onset RA patients with 3 years of clinical and radiological follow-up, and TIRx patients (n = 104) with ACPA IgG and musculoskeletal pain followed for 290 weeks (median). Blood donors and three different chronic inflammatory diseases served as controls. Free SC was analysed by sandwich ELISA. RESULTS: Serum levels of free SC were significantly higher in TIRA-2 patients compared with TIRx and all control groups (P < 0.01). Among TIRx patients who subsequently developed arthritis, free SC levels were higher compared with all control groups (P < 0.05) except ankylosing spondylitis (P = 0.74). In TIRA-2, patients with ACPA had higher baseline levels of free SC compared with ACPA negative patients (P < 0.001). Free SC status at baseline did not predict radiographic joint damage or disease activity over time. In TIRx, elevated free SC at baseline trendwise associated with arthritis development during follow-up (P = 0.066) but this disappeared when adjusting for confounders (P = 0.72). Cigarette smoking was associated with higher levels of free SC in both cohorts. CONCLUSION: Serum free SC levels are increased in recent-onset RA compared with other inflammatory diseases, and associate with ACPA and smoking. Free SC is elevated before arthritis development among ACPA positive patients with musculoskeletal pain, but does not predict arthritis development. These findings support mucosal engagement in RA development.

A pilot study of forearm microvascular impairment and pain while using a telephone.

OBJECTIVE: To determine if using a telephone can induce forearm pain and ischemia. DESIGN: Prospective case-control trial. SETTING: Vascular laboratory in the university hospital in Angers between September 2018 and March 2019. PARTICIPANTS: Fifteen apparently healthy subjects (controls) and 32 patients with suspected thoracic outlet syndrome (TOS) of vascular or non-vascular origin. INTERVENTION: Hand-holding a cellular phone to answer a call from investigators. MAIN OUTCOME MEASURES: Presence of forearm fatigue or pain (primary outcome), ability to hold the phone with each hand for 1 min (secondary outcome 1) and decrease in forearm transcutaneous oxygen pressure DROP index indicating forearm ischemia (secondary outcome 2). A DROP < -15 mm Hg defined ischemia. RESULTS: Answering a phone call resulted in 25(78%) patients with forearm fatigue or pain and in 18 (56%) cases in the inability to hold the phone for 1 min, on one or both arms in patients with suspected TOS, but never occurred in healthy volunteers (p < .05 and p < .001). The presence of ischemia was observed in one or both arms in 10 (31%) patients with proved TOS and was always associated to phone-induced pain. Three (20%) of the controls had phone-induced ischemia. All had asymptomatic TOS and remained asymptomatic during the phone test (p = .42 from suspected-TOS patients). CONCLUSION: The phone conversation resulted in pain in many patients with suspected TOS. Transcutaneous oximetry can document the underlying ischemia. Forearm phone-call-induced pain may be indicative of TOS provided that no earplug or headset is used. Trial registrationClinicalTrials.govNCT03355274.

Translation, cross-cultural adaptation, and measurement properties of the Nepali version of the central sensitization inventory (CSI).

BACKGROUND: Central sensitization is thought to be an important contributing factor in many chronic pain disorders. The Central Sensitization Inventory (CSI) is a patient-reported measure frequently used to assess symptoms related to central sensitization. The aims of the study were to translate and cross-culturally adapt the CSI into Nepali (CSI-NP) and assess its measurement properties. METHODS: The CSI was translated into Nepali using recommended guidelines. The CSI-NP was then administered on 100 Nepalese adults with sub-acute and chronic musculoskeletal pain with additional demographic and pain-related questions. The CSI-Nepali was administered again about 2 weeks later. Four measurement properties of the CSI-NP were evaluated: (1) internal consistency using Cronbach's alpha, (2) test-retest reliability using intraclass correlation coefficient (ICC2,1), (3) measurement errors, and (4) construct validity testing five a priori hypotheses. Confirmation of construct validity was determined if a minimum of 75% of the hypotheses were met. RESULTS: The CSI was successfully translated into Nepali. Internal consistency and test-retest reliability were both excellent (Cronbach's alpha = 0.91, and ICC = 0.98). The standard error of measurement was 0.31 and the smallest detectable change was 0.86. Four out of five (80%) a priori hypotheses were met, confirming the construct validity: the CSI-NP correlated strongly with the Pain Catastrophizing Scale total scores (r = 0.50); moderately with the total number of pain descriptors (r = 0.35); weakly with the Numerical Rating Scale (r = 0.25); and women had significantly higher CSI scores than men. However, the CSI scores did not correlate significantly with the total duration of pain, as hypothesized (r = 0.10). CONCLUSIONS: The Nepali translation of the CSI demonstrated excellent reliability and construct validity in adults with musculoskeletal pain. It is now available to Nepali health care providers to help assess central sensitization-related signs and symptoms in individuals with musculoskeletal pain in research or clinical practice to advance the understanding of central sensitization in Nepalese samples.