Growth Differentiation Factor 15 as a Biomarker of Cardiovascular Risk in Chronic Musculoskeletal Pain.

BACKGROUND: It is unknown whether growth differentiation factor 15 (GDF-15) is associated with chronic musculoskeletal pain (CMP) and whether or not its association with incident cardiovascular disease (CVD) changes according to CMP status. METHODS: In total, 1 957 randomly selected adults aged ≥65 years without prior CVD were followed up between 2015 and 2023. CMP was classified according to its intensity, frequency, and interference with daily activities. The association between GDF-15 levels and CMP was assessed using linear models with progressive inclusion of potential confounders, whereas the association between GDF-15 and CVD risk was evaluated with Cox proportional hazard models with similar adjustment and interaction terms between GDF-15 and CMP. The incremental predictive performance of GDF-15 over standard predictors was evaluated using discrimination and risk reclassification metrics. RESULTS: GDF-15 concentrations were 6.90% (95% confidence interval [CI]: 2.56; 11.25) higher in individuals with CMP, and up to 8.89% (4.07; 15.71) and 15.79% (8.43; 23.16) higher in those with ≥3 CMP locations and interfering pain. These increased levels were influenced by a higher prevalence of cardiometabolic risk factors, functional impairments, depressive symptoms, and greater levels of inflammation in individuals with CMP. In fully adjusted models, a twofold increase in GDF-15 was associated with a 1.49 increased risk (95% CI: 1.08; 2.05) of a CVD event in individuals with CMP, but not among those without CMP (1.02 [0.77; 1.35]); p-interaction 0.041. Adding GDF-15 to models including the Framingham Risk Score improved predictive performance among individuals with CMP. CONCLUSIONS: We provide evidence that GDF-15 could serve as a biomarker to assess CMP, as well as to predict CVD incidence in individuals with CMP.

Severity of premenstrual symptoms among women with musculoskeletal pain: relation to vitamin D, calcium, and psychological symptoms.

Premenstrual syndrome (PMS) has various symptoms that occur during the luteal phase of the menstrual cycle and subside after menstruation. Anxiety and depression are prevalent in women with PMS and may exacerbate the severity of PMS. Vitamin D and calcium deficiency may have a role in developing anxiety, depression, and musculoskeletal pain (MSP). The aim of this study was to evaluate selected premenstrual symptoms in relation to serum vitamin D levels, daily calcium consumption, and psychological symptoms among women with MSP. The study population consisted of 108 women with MSP and 108 healthy controls. Information about premenstrual symptoms and calcium consumption were collected. Psychological symptoms were assessed using the Hospital Anxiety and Depression Scale (HADS). Vitamin D was determined by electrochemiluminescence immunoassay. Women with MSP had lower serum vitamin D levels, lower daily calcium consumption, higher HADS scores for anxiety and depression, and higher frequency of severe premenstrual symptoms including fatigue, headache, irritability, mood swings, anxiety, depression, and social withdrawal compared to controls (P < 0.01). Abnormal HADS scores for anxiety and depression were associated with increased severity of premenstrual symptoms (P < 0.05). Deficient vitamin D and calcium consumption were associated with abnormal HADS scores for anxiety and depression (P < 0.05) and with increased severity of premenstrual headache, irritability, anxiety, and depression (P < 0.05). Low calcium consumption was associated with increased severity of premenstrual irritability, anxiety, depression, and social withdrawal (P < 0.05). The results suggest that vitamin D deficiency, low calcium consumption, psychological symptoms, and MSP could be interrelated and implicated in the etiology severe premenstrual symptoms. Further studies are necessary to assess whether vitamin D and calcium supplements can relieve MSP and premenstrual symptoms.

Serum Vitamin D and Chronic Musculoskeletal Pain: A Cross-Sectional Study of 349,221 Adults in the UK.

Insufficient and deficient vitamin D may be associated with chronic musculoskeletal pain, but study findings are conflicting, and few account for important confounding factors. This cross-sectional study explored the association between serum vitamin D status and chronic musculoskeletal pain in various body sites, adjusting for a wide range and a number of potential confounding factors. Data collected at the baseline assessments of 349,221 UK Biobank participants between 2006 and 2010 were analyzed. Serum 25-hydroxyvitamin D was measured and categorized as <25.0 nmol/L (severe deficiency), 25.0 to 49.9 nmol/L (deficiency), 50.0 to 74.9 nmol/L (insufficiency), and ≥75.0 nmol/L (sufficiency). The outcome was self-reported chronic musculoskeletal pain at any site, neck/shoulder, back, hip, knee, or widespread pain that interfered with usual activities. Potential confounders were identified using directed acyclic graphs and included sociodemographic, lifestyle, psychological factors, and medical comorbidities. Simple models adjusted for age and sex showed significant associations between suboptimal vitamin D status and chronic pain across all sites (odds ratios [ORs] ranged 1.07-2.85). These associations were weakened or became insignificant after accounting for all confounding factors (ORs ≤ 1.01) for chronic regional musculoskeletal pain. Severe vitamin D deficiency remained a significant and positive association with chronic widespread pain after adjusting for all confounding factors (OR [95% confidence interval]: 1.26 [1.07, 1.49]). This study suggests that, while vitamin D status is not a key independent determinant of chronic regional musculoskeletal pain, severe vitamin D deficiency may be associated with chronic widespread pain. PERSPECTIVE: After accounting for various confounders, vitamin D deficiency was not associated with regional musculoskeletal pain. However, the relationship between chronic widespread pain severe vitamin D deficiency remained after confounder adjustment. Use of vitamin D supplements in individuals with chronic widespread pain and severe vitamin D deficiency warrants further exploration.

A 3-Year-Old With Gingival Hemorrhage and Musculoskeletal Pain.

A 3-year-old had spontaneous gingival hemorrhage and bilateral limb weakness with inability to bear weight. He had no preceding oral trauma or recent infection, took no regular medications, and had no recent use of aspirin or nonsteroidal anti-inflammatory drugs; his diet was limited to primarily chicken nuggets and milk. What is the diagnosis and what would you do next?

Disentangling Associations Between Serum Muscle Biomarkers and Sarcopenia in the Presence of Pain and Inflammation Among Patients With Osteoarthritis: The SPSS-OK Study.

BACKGROUND/OBJECTIVE: Reduction of muscle markers, such as creatine phosphokinase (CK), in rheumatic diseases and its association with reduced muscle mass may be of clinical importance in osteoarthritis (OA). Considering the complexity of secondary sarcopenia, clarifying the association between muscle markers and sarcopenia and disentangling the involvement of OA-related conditions are of clinical importance. We investigated the association between serum muscle biomarkers and sarcopenia among patients with OA, considering the presence of pain and inflammation. METHODS: Overall, 1425 patients with knee and hip OA scheduled for joint replacement surgery were included in a single-center cross-sectional study from Screening for People Suffering Sarcopenia in Orthopedic cohort of Kobe study. Primary outcome was sarcopenia defined by 2 criteria (the Asian Working Group for Sarcopenia and the European Working Group on Sarcopenia in Older People). Pain and inflammation were measured using the numeric rating scale and serum C-reactive protein (CRP) levels, respectively. Associations between the biomarkers (serum CK, aspartate aminotransferase, alanine aminotransferase) and sarcopenia were examined using logistic regression models. RESULTS: Sarcopenia by the Asian Working Group for Sarcopenia criteria was present in 4.0% of patients. In adjusted analyses, sarcopenia was negatively associated with higher serum CK levels, but not with serum aspartate aminotransferase or alanine aminotransferase levels independent of pain score and serum CRP. Neither pain score nor serum CRP level was associated with sarcopenia. Similar results were found when the European Working Group on Sarcopenia in Older People criteria were used. CONCLUSIONS: Serum CK was associated with sarcopenia, suggesting the potential usefulness for sarcopenia detection regardless of pain or inflammation in OA.

Autoantibodies are major predictors of arthritis development in patients with anti-citrullinated protein antibodies and musculoskeletal pain.

Objectives: Predictors of arthritis development are highly warranted among patients with anti-citrullinated protein antibodies (ACPAs) and musculoskeletal symptoms to optimize clinical management. We aimed to identify clinical and laboratory predictors of arthritis development, including biochemically assessed alcohol consumption, among ACPA-positive patients with musculoskeletal pain.Method: 82 ACPA-positive individuals with musculoskeletal pain but no clinical arthritis were followed for a median of 72 months (interquartile range 57-81 months). We evaluated the prognostic value of baseline clinical and laboratory factors including smoking, symptom duration, age, gender, shared epitope, rheumatoid factor (RF), anti-carbamylated protein antibodies, ACPA levels, erythrocyte sedimentation rate, C-reactive protein levels, tender joint count, patient-reported general well-being, 28-joint Disease Activity Score, and alcohol consumption as measured by phosphatidyl ethanol (PEth) levels in whole blood.Results: During follow-up, 48% developed at least one arthritis. Multivariable analysis revealed an increased risk of arthritis development with RF positivity [hazard ratio (HR) = 2.3, 95% confidence interval (CI) 1.1-4.8, p = 0.028] and higher ACPA levels (HR = 1.0, 95% CI 1.000-1.001, p = 0.002). High levels of RF (HR = 4.4, 95% CI 1.7-11) entailed the highest HR in this ACPA-positive population. Neither clinical characteristics nor alcohol consumption measured by PEth conferred significant prognostic value.Conclusions: ACPA levels and concurrent presence of RF are independent predictors of arthritis development among ACPA-positive patients with musculoskeletal pain. The results are compatible with a dose-response relationship between RA-related autoantibodies and risk of arthritis development.

Enrichment of genomic pathways based on differential DNA methylation profiles associated with chronic musculoskeletal pain in older adults: An exploratory study.

Our study aimed to identify differentially methylated CpGs/regions and their enriched genomic pathways associated with underlying chronic musculoskeletal pain in older individuals. We recruited cognitively healthy older adults with (n = 20) and without (n = 9) self-reported musculoskeletal pain and collected DNA from peripheral blood that was analyzed using MethylationEPIC arrays. We identified 31,739 hypermethylated CpG and 10,811 hypomethylated CpG probes (ps ≤ 0.05). All CpG probes were clustered into 5966 regions, among which 600 regions were differentially methylated at p ≤ 0.05 level, including 294 hypermethylated regions and 306 hypomethylated regions (differentially methylated regions). Ingenuity pathway enrichment analysis revealed that the pain-related differentially methylated regions were enriched across multiple pathways. The top 10 canonical pathways were linked to cellular signaling processes related to immune responses (i.e. antigen presentation, programed cell death 1 receptor/PD-1 ligand 1, interleukin-4, OX40 signaling, T cell exhaustion, and apoptosis) and gamma-aminobutyric acid receptor signaling. Further, Weighted Gene Correlation Network Analysis revealed a comethylation network module in the pain group that was not preserved in the control group, where the hub gene was the cyclic adenosine monophosphate-dependent transcription factor ATF-2. Our preliminary findings provide new epigenetic insights into the role of aberrant immune signaling in musculoskeletal pain in older adults while further supporting involvement of dysfunctional GABAergic signaling mechanisms in chronic pain. Our findings need to be urgently replicated in larger cohorts as they may serve as a basis for developing and targeting future interventions.

Association of high sensitivity C-reactive protein with tearing of the long head of the biceps tendon.

BACKGROUND: This study proposed to investigate whether high-sensitivity C-reactive protein (hs-CRP) is an independent risk factor for long head of biceps tendon (LHBT) tear and whether hs-CRP can increase accuracy in diagnosing LHBT tear. METHODS: This study involved 582 shoulders of 557 consecutive patients who received arthroscopic examinations at the authors' institution between January 2010 and July 2018. The strengths of associations between LHBT tear and various factors were determined by calculating the odds ratios (ORs), with 95% confidence intervals (CIs), using logistic regression analyses. The studied variables were demographic, physical, social, metabolic, comorbidity, hs-CRP, and pain on a visual analog scale (VAS) factors, as well as those related to rotator cuff tear (RCT). Significant factors in the multivariable logistic analysis were evaluated to determine their diagnostic values, including their likelihood ratios and post-test probabilities for LHBT tear. RESULTS: In the multivariable analysis, five variables were significant: age, retraction degree of Patte, subscapularis tendon tear, hs-CRP > 1 mg/L, and pain VAS (p ≤ 0.01). The best combination of determinations for diagnosing LHBT tear, which yielded a strong positive likelihood ratio of 19.07 and a high post-test probability of 96%, was age ≥ 67 years, subscapularis tendon tear, grade of Patte ≥2, hs-CRP > 1, and pain VAS ≥ 7. CONCLUSIONS: Serum hs-CRP > 1 mg/L is an independent risk factor for LHBT tear, along with the expected risk factors of age, subscapularis tendon tear, retraction degree of Patte, and pain VAS. Serum hs-CRP > 1 mg/L increases the diagnostic accuracy for LHBT tear. LEVEL OF EVIDENCE: Level IV, Clinical case series.

The association between chronic musculoskeletal pain and clinical outcome in chronic kidney disease patients: a prospective cohort study.

BACKGROUND AND OBJECTIVES: Chronic musculoskeletal (MS) pain is common in chronic kidney disease (CKD) patients. The association of chronic MS pain and CKD progression has not yet been established. METHOD: We conducted a prospective cohort study to evaluate the association of chronic MS pain and CKD progression of pre-dialysis CKD patients. RESULT: A total of 53.2% of pre-dialysis CKD patients had chronic MS pain. Patients classified as progression and non-progression had a similar prevalence of chronic MS pain at baseline, and similar baseline use of NSAIDs and Chinese herbal medicines. Univariate Cox analysis indicated that chronic MS pain and baseline NSAID or Chinese herbal medicine use were not significantly associated with progression of CKD. But multivariate Cox regression found chronic MS pain was independently significantly associated with all-cause mortality (HR, 2.912, 95% CI, 1.004-8.444; p = .049). However, serum levels of hs-CRP were similar between those chronic MS pain patients and without chronic MS pain patients (4.96 ± 9.4 vs. 4.25 ± 13.3 mg/L, p = .535). CONCLUSION: The CKD patients with chronic MS pain was independently and significantly associated with all-cause mortality, but not independently and significantly associated with CKD progression and composite endpoints. The inflammatory marker-hs-CRP was similar between CKD patients with and without chronic MS pain.

Association of CCL2 with systemic inflammation in Schnitzler syndrome.

BACKGROUND: Schnitzler syndrome (SchS) is a rare autoinflammatory disease characterized by urticarial exanthema, bone and joint alterations, fever and monoclonal gammopathy, which manifest mostly in the second half of life. It involves overactivation of the interleukin (IL)-1 system, but the exact pathophysiological pathways remain largely unknown. OBJECTIVES: To identify and characterize the pathogenetic players in SchS. METHODS: Blood parameters were quantified in patients with SchS compared with healthy controls and patients with psoriasis and hidradenitis suppurativa using enzyme-linked immunosorbent assay (ELISA). CCL2 expression in cultured primary cells was analysed by quantitative reverse-transcriptase polymerase chain reaction and ELISA. RESULTS: CCL2, a chemoattractant for monocytic and further mononuclear immune cells, was found to be significantly elevated in patients with SchS. CCL2 levels showed a positive association with global disease activity, especially with bone pain, but not disease duration, gammopathy, neutrophilia or skin disease. In vitro stimulation assays demonstrated a strong CCL2 production capacity of mononuclear immune cells and fibroblasts, but not epithelial or endothelial cells. Among a range of inflammatory mediators, only IL-1ß (immune cells, fibroblasts) and tumour necrosis factor (TNF)-α (fibroblasts) were important CCL2 inducers. TNF-α, but not IL-17, strengthened the CCL2-inducing effect of IL-1ß in fibroblasts. Accordingly, CCL2 levels positively correlated with both TNF-α and IL-1ß serum levels in patients with SchS. Therapeutic IL-1ß blockade decreased CCL2 blood levels in these patients as early as 1 week after the initiation of treatment. CONCLUSIONS: CCL2 may be an important component of the pathogenetic cascade leading to bone alterations, and a suitable marker of disease activity in patients with SchS.

Reduced dose pegfilgrastim is associated with less bone pain without increased neutropenia: a retrospective study.

BACKGROUND: Chemotherapy for breast cancer is associated with a high risk of neutropenia. Pegfilgrastim reduces the risk of neutropenic fever but commonly causes bone pain. OBJECTIVE: Evaluate whether a reduced dose of pegfilgrastim (3 mg) reduced the frequency of bone pain without compromising efficacy. METHODS: Records reviewed from breast cancer patients who received at least one 3 mg dose of pegfilgrastim, white blood count (WBC), and absolute granulocyte counts (AGC) were collected. Musculoskeletal pain scale was collected at each visit. RESULTS: 265 treatments from 36 women were analyzed. There was no difference in post-treatment AGC between 3 versus 6 mg. Leukocytosis (WBC > 20,000 cells/cu mm) was more likely for those treated with 6 mg (chi-square 5.265, p = 0.0215). There was higher change in bone pain in patients who received 6 mg doses compared to none or 3 mg. LIMITATIONS: In this retrospective, non-randomized study, we found the majority of patients received the reduced 3 mg dose after intolerance to the 6 mg dose. It is unknown if smaller or larger doses than 3 mg would achieve similar results or whether 3 mg dose would be effective as an initial therapy or for patients receiving different chemotherapy regimens. Pain is observed despite premedication with naproxen and/or loratidine. CONCLUSION: Reduced dose of pegfilgrastim 3 mg was less likely to cause bone pain. The reduced dose was not associated with a significant difference in post-treatment AGC or rate of serious infection.

Vitamin D deficiency is associated with tibial bone pain and tenderness. A possible contributive role.

BACKGROUND: Vitamin D deficiency is associated with osteomalacia and a variety of musculoskeletal pain. This study aimed to determine the association of vitamin D deficiency with tibial bone pain and tenderness. METHODS: Patients with leg pain, defined as local pain and tenderness over tibial bones for ≥ 6 weeks were consecutively selected. Secondary causes of pain were excluded by appropriate clinical, radiological and laboratory examinations. Serum 25-hydroxyvitamin D (25-OHD) was assessed by enzyme-linked immunosorbent assay method and levels < 20 ng/mL were considered as deficiency. Age- and sex-matched subjects without leg pain served as controls. Multiple logistic regression analysis was used to determine associations. RESULTS: One hundred and eighteen patients and 114 controls aged 46.8 ± 14.8 and 44.6 ± 14.1 years, respectively (P = 0.93) were analyzed. Mean 25-OHD level was significantly lower (P = 0.001) and the prevalence of 25-OHD deficiency was significantly higher in the patients as compared with the controls (75.4% vs. 23.6%), odds ratio (OR) = 9.54 (95% CI, 5.22-17.45, P = 0.001). There was a negative dose-response relationship between serum 25-OHD and tibial bone pain by OR = 17.33 (95% CI, 6.48-46.3) in subjects with 25-OHD < 10 ng/mL, and OR = 14.7 (95% CI, 6.35-34.6) in serum 25-OHD levels at 10-19.9 ng/mL, and OR = 2.58 (95% CI, 1.08-6.1) in those with 25-OHD at 20-29.9 ng/mL as compared with 25-OHD ≥ 30 ng/mL. After controlling for demographic and biochemical factors, the association reached a stronger level of 19.8 (6.9-56.3) in subjects with serum 25-OHD < 10 ng/mL and 14.4 (5.8-34.6) in those with serum 25-OHD at levels of 10-19.9 ng/mL and 1.85 (0.73-4.6) in 20-29 ng/mL. CONCLUSION: These findings indicate a possible contributive role for serum 25-OHD deficiency in the development of pain and tenderness over the tibial bone.

Association between cortisol levels and pain threshold in systemic sclerosis and major depression.

Pain perception and threshold show complex interactions with the inflammatory, psychiatric and neuroendocrine stimuli. This study aims to test whether lower serum cortisol levels are associated with lower pain thresholds and higher degree of depression in systemic sclerosis (SSc) and major depression with atypical features (MD-AF) patients compared to controls. 180 female subjects (SSc = 60, MD-AF = 60, healthy controls = 60) participated in this observational, cross-sectional, parallel group study. Pressure pain threshold (PPT) was assessed in three anatomical sites: nail bed (NB), metacarpophalangeal joint (MCP) and quadriceps muscle (QDR). Depressive symptoms were evaluated using the Beck Depression Inventory (BDI) scale and morning serum cortisol levels were collected. In SSc patients, quality of life was measured through the Health Assessment Questionnaire (HAQ-DI) and the scleroderma-specific visual analogue scales (scleroderma-VAS). Lower PPT scores (NB 4.42 ± 1.6; MCP 4.66 ± 1.4; QDR 4.79 ± 1.5) were observed in SSc patients compared to both MD-AF (NB 7.33 ± 2.2; MCP 6.01 ± 1.9; QDR 6.31 ± 1.6; p < 0.005) and controls (NB 9.57 ± 2; MCP 7.9 ± 2.1 and QDR 8.43 ± 2.1; p < 0.0001), while MD-AF patients had lower PPT scores compared to controls (p < 0.0001). SSc patients had also lower serum cortisol levels compared to MD-AF patients (8.78 vs 13.6 µg/dl; p < 0.05). A direct correlation was observed between serum cortisol and PPT scores both in SSc (r 2 for NB 0.29; for MCP 0.25; for QDR 0.27) and in MD-AF (r 2 for NB 0.34; for MCP 0.25; for QDR 0.47; p < 0.05), while depressive symptoms negatively correlated with serum cortisol (r 2 for NB 0.34; for MCP 0.17; for QDR 0.15) and in MD-AF (r 2 for NB 0.19; for MCP 0.31; for QDR 0.30; p < 0.05). Among SSc patients, those with serum cortisol levels below the normal range (n = 16) had higher BDI scores (15, 6-21 vs 9, 2-15; p < 0.005), lower PPTs (NB 4 ± 1.4 vs 4.9 ± 0.9; MCP 4.1 ± 0.8 vs 4.8 ± 0.9; QDR 4.1 ± 1.2 vs 5 ± 0.9; p < 0.005) and higher HAQ-DI (1.25, 0.25-2 vs 0.75, 0-1.25; p < 0.05) and scleroderma-VAS scores (VAS overall severity 7, 5.5-9.5 vs 4.5, 2.5-6; p < 0.05). The effect of cortisol serum levels upon pain mechanism, in chronic inflammatory conditions warrants longitudinal studies to detect treatable variations in pain thresholds, depressive symptoms and to improve quality of life.

Circulating Lipids and Acute Pain Sensitization: An Exploratory Analysis.

BACKGROUND: In individuals with low back pain, higher lipid levels have been documented and were associated with increased risk for chronic low back pain. OBJECTIVES: The purpose of this research was to identify plasma lipids that discriminate participants with acute low back pain with or without pain sensitization as measured by quantitative sensory testing. METHODS: This exploratory study was conducted as part of a larger parent randomized controlled trial. A cluster analysis of 30 participants with acute low back pain revealed two clusters: one with signs of peripheral and central sensitivity to mechanical and thermal stimuli and the other with an absence of peripheral and central sensitivity. Lipid levels were extracted from plasma and measured using mass spectroscopy. RESULTS: Triacylglycerol 50:2 was significantly higher in participants with peripheral and central sensitization compared to the nonsensitized cluster. The nonsensitized cluster had significantly higher levels of phosphoglyceride 34:2, plasmenyl phosphocholine 38:1, and phosphatidic acid 28:1 compared to participants with peripheral and central sensitization. Linear discriminant function analysis was conducted using the four statistically significant lipids to test their predictive power to classify those in the sensitization and no-sensitization clusters; the four lipids accurately predicted cluster classification 58% of the time (R = .58, -2 log likelihood = 14.59). DISCUSSION: The results of this exploratory study suggest a unique lipidomic signature in plasma of patients with acute low back pain based on the presence or absence of pain sensitization. Future work to replicate these preliminary findings is underway.

Pain involving the motor system and serum vitamin D concentration in postmenopausal women working in agriculture.

INTRODUCTION AND OBJECTIVE: Since the role of vitamin D is essential in numerous biological processes its deficiency was suggested to be a risk factor for e.g. osteoporosis, musculoskeletal pain and spine pain. The purpose of the study was to analyse whether serum vitamin D concentration is related to pain involving the motor system in Polish postmenopausal women working in agriculture. MATERIAL AND METHODS: The study group consisted of 1,751 post-menopausal women, aged 45-65, at least 12 months from the last menstrual period, living in rural areas and working in agriculture. The research method was self-assessment of pain involving the motor system using VAS, laboratory test of serum vitamin D concentration and a medical interview. Statistical methods included generalized linear models, analysis of variance, t test for two means in two independents, χ2 test of stochastic independence. RESULTS: Postmenopausal women working in agriculture and suffering from pain in at least one part of the motor system were younger and lower educated, they also had higher abdominal obesity and lower serum vitamin D, compared to those without pain in any part of the motor system. Decreased serum vitamin D concentration in postmenopausal women working in agriculture is important from the aspect of a higher prevalence of pain in the thoracic spine and more severe pain in the neck spine, but not for severity of pain in the lumbar spine; higher occurrence of pain in both hands or wrists; higher prevalence and more severe pain in at least one knee; and no prevalence or severity of pain in the shoulders and elbows. CONCLUSION: Serum vitamin D concentration is important for the prevalence and severity of pain in the neck and thoracic spine, knees and hands or wrists, but not for the lumbar spine, shoulders and elbows.

Up-regulated exosomal miRNA-140-3p in CML patients with musculoskeletal pain associated with discontinuation of tyrosine kinase inhibitors.

We analyzed the exosomal miRNA from peripheral blood from CML patients with musculoskeletal pain after stopping tyrosine kinase inhibitors to identify possible factors related to this manifestation. Exosomal miRNA profiling using TaqMan low-density array revealed that exosomal miR-140-3p was significantly elevated in CML patients showing musculoskeletal pain, when compared to those without such pain (P = 0.0336) or healthy individuals (P = 0.0022). All five CML patients with musculoskeletal pain and increased exosomal miR-140-3p levels sustained deep molecular responses: four of them achieved symptom relief and a significant decrease in exosomal miR-140-3p levels was evident. Because exosomal miR-140-3p is considered to have an inflammation-associated biological function in airway smooth muscle cells and targets Myomarker muscle-specific transmembrane protein, it appears that its overexpression in circulating exosomal miR-140-3p may have some role in the mechanism underlying self-limited musculoskeletal pain.

Obesity is associated with a higher prevalence of musculoskeletal pain in middle-aged women.

Musculoskeletal pain (MSP) has been recently linked with high plasma leptin levels. Our objective was to study if obese women, who have higher leptin levels, could have a higher frequency of MSP. We studied 6079 Latin-American women, 40-59 years old. Their epidemiological data were recorded and the Menopause Rating Scale (MRS), Golberg Anxiety and Depression Scale and Insomnia Scale were applied. MSP was defined as a score ≥2 on MRS11. Women with MSP were slightly older, had fewer years of schooling and were more sedentary. They also complained of more severe menopausal symptoms (29.2% versus. 4.4%, p < 0.0001). Furthermore, they had a higher abdominal perimeter (87.2 ± 12.0 cm versus 84.6 ± 11.6 cm, p < 0.0001) and a higher prevalence of obesity (23.1% versus 15.2%, p < 0.0001). Compared to normal weight women, those with low body weight (IMC <18.5) showed a lower risk of MSP (OR 0.71; 95%CI, 0.42-1.17), overweight women had a higher risk (OR 1.64; 95%CI, 1.44-1.87) and obese women the highest risk (OR 2.06; 95%CI, 1.76-2.40). Logistic regression analysis showed that obesity is independently associated to MSP (OR 1.34; 95%CI, 1.16-1.55). We conclude that obesity is one identifiable risk factor for MSP in middle-aged women.

Effects of Chronic Musculoskeletal Pain on Fertility Potential in Lean and Overweight Male Patients.

Both chronic pain and obesity are known to affect reproductive hormone profiles in male patients. However, the effect of these conditions, alone or in combination, on male fertility potential has received less attention. 20 chronic musculoskeletal pain patients and 20 healthy controls were divided into lean and overweight subgroups according to their BMI. Current level of chronic pain (visual analogue scale) and pressure pain thresholds (PPTs) in 16 predefined sites, classically described and tested as painful points on the lower body, were measured. Levels of reproductive hormone and lipid profiles were assessed by ELISA. Sperm concentration and motility parameters were analyzed using a computer-aided sperm analysis system. Sperm concentration, progressive motility, and percentage of hyperactivated sperm were generally lower in the chronic pain patients in both lean and overweight groups. The overweight control and the lean chronic pain groups demonstrated a significantly lower percentage of progressively motile sperm compared with the lean control group, suggesting that musculoskeletal chronic pain may have a negative influence on sperm quality in lean patients. However, due to the potential great negative influence of obesity on the sperm parameters, it is difficult to propose if musculoskeletal chronic pain also influenced sperm quality in overweight patients. Further research in chronic pain patients is required to test this hypothesis.