Objectives
Chronic widespread pain (CWP) is a common disorder affecting ~10% of the general population and has an estimated heritability of 48-52%. In the first large-scale genome-wide association study (GWAS) meta-analysis, we aimed to identify common genetic variants associated with CWP.
Methods
We conducted a GWAS meta-analysis in 1,308 female CWP cases and 5,791 controls of European descent, and replicated the effects of the genetic variants with suggestive evidence for association in 1,480 CWP cases and 7,989 controls (P<1×10−5). Subsequently, we studied gene expression levels of the nearest genes in two chronic inflammatory pain mouse models, and examined 92 genetic variants previously described associated with pain.
Results
The minor C-allele of rs13361160 on chromosome 5p15.2, located upstream of CCT5 and downstream of FAM173B, was found to be associated with a 30% higher risk of CWP (MAF=43%; OR=1.30, 95%CI=1.19-1.42, P=1.2×10−8). Combined with the replication, we observed a slightly attenuated OR of 1.17 (95%CI=1.10-1.24, P=4.7×10−7) with moderate heterogeneity (I2=28.4%). However, in a sensitivity analysis that only allowed studies with joint-specific pain, the combined association was genome-wide significant (OR=1.23, 95%CI=1.14-1.32, P=3.4×10−8, I2=0%). Expression levels of Cct5 and Fam173b in mice with inflammatory pain were higher in the lumbar spinal cord, not in the lumbar dorsal root ganglions, compared to mice without pain. None of the 92 genetic variants previously described were significantly associated with pain (P>7.7×10−4).
Conclusions
We identified a common genetic variant on chromosome 5p15.2 associated with joint-specific CWP in humans. This work suggests that CCT5 and FAM173B are promising targets in the regulation of pain.
Chronic pain is more prevalent in women than in men, with increasing differences between sexes in advanced age. This could be caused by differences in sex hormone levels. We therefore studied the relationship between sex hormones and the prevalence and incidence of chronic pain. The association between sex hormone levels and chronic pain was examined in 9717 participants aged 45 years and older from the Rotterdam Study, a population-based study. Chronic pain was defined as pain in the lower back, hands, knees and/or hips for at least 3 months. Sex hormone levels included estrogen, testosterone, androstenedione, and 17-hydroxyprogesterone. Relationships between hormones and prevalent and new onset chronic pain were analyzed using linear and logistic regression, stratified by gender. Women with androstenedione or estradiol levels in the lowest tertile had more chronic pain (odds ratio, 1.20; 95% CI, 1.03-1.39 and odds ratio, 1.27; 95% CI, 1.10-1.48, respectively). Mean estradiol levels were lower among men with chronic pain (mean difference -3.88 pmol/L; P = 0.005). Lowest tertile 17-hydroxyprogesterone in women was associated with 38% more new onset pain. All these associations were independent from age, body mass index, health and lifestyle factors, and osteoarthritis. Lower sex hormone levels are associated with chronic musculoskeletal pain, independent from lifestyle and health-related factors, in community-dwelling elderly women. These results suggest that sex hormones play a role in chronic pain and should be taken into account when a patient presents with chronic pain. Therefore, sex hormones may be a potential treatment target for these patients.
BACKGROUND AND PURPOSE:Central sensitization in chronic pain involves structural brain changes that influence vulnerability to pain. Identifying brain regions involved in pain processing and sensitization can provide more insight into chronic pain. This study examines structural brain changes in chronic pain and experimental pain in a large population-based study.
Objective. Type 3 finger length pattern (longer fourth digit than second digit) is influenced by prenatal androgens and has been studied previously as a biomarker for sexually dimorphic traits. Because osteoarthritis (OA) and chronic pain are known to be sexually dimorphic traits, we evaluated the association between finger length pattern and OA and chronic joint pain. Methods. This study was part of the Rotterdam Study, a prospective population-based cohort study. We examined 4,784 participants. Associations between type 3 finger length and radiologic knee, hip, and hand OA and chronic joint pain were analyzed using a logistic regression model. Our results for OA were combined with previously published data in a meta-analysis. Results. Participants with type 3 finger length pattern had an odds ratio of 1.64 for hand OA (P ؍ 1.06 ؋ 10 ؊7 ). No associations with radiologic knee or hip OA were observed in the Rotterdam Study. The meta-analysis of previously published data and our novel data showed a significant association between type 3 finger length pattern and clinical symptomatic knee OA, but no association was found with radiologic knee OA. In addition, within the Rotterdam Study, we observed an odds ratio of 1.41 for individuals having joint pain at multiple sites (P ؍ 1.4 ؋ 10 ؊3 ). Conclusion. Type 3 finger length pattern, as an indicator of prenatal androgen exposure, was associated with having symptomatic knee OA, chronic pain, and hand OA. Therefore, it may be applicable as an easy measurable biomarker to identify susceptible subjects for these traits.
Higher sensitivity for heat pain, one feature of central sensitization, is present in community-dwelling elderly with chronic pain. Additional determinants should be considered when analyzing and interpreting QST measurements.
BackgroundOver 75 % of patients presenting with a proximal humerus fracture are 70 years or older. Very little is known about the outcome after operative treatment of these fractures in very old patients. This study was performed to gain more insight in safety and functional outcome of surgical treatment of proximal humerus fractures in the elderly.Materials and methodsIn this observational study, we analyzed all operatively treated patients, aged 75 or older, with a proximal humerus fracture between January 2003 and December 2008 in our center. Patient selection was on clinical grounds, based on physical, mental, and social criteria. Complications were evaluated. We used the DASH Questionnaire to investigate functional outcome, pain, and ADL limitations.ResultsSixty-four patients were treated surgically for a displaced proximal fracture of the humerus: 15 two-part, 32 three-part, and 17 four-part fractures. Mean DASH scores were 37.5, 36.9, and 48.6, respectively. Regarding the operative methods, overall good results were obtained with the modern locked plate osteosynthesis (mean DASH 34.4). Prosthetic treatment, mostly used in highly comminuted fractures, often resulted in poor function (mean DASH 72.9). Persistent pain and ADL limitations were more present in more comminuted fractures (64 and 50 % in patients with 4-part fractures vs. 14 % in 2-part fractures). There were no postoperative deaths within 3 months of surgery, and fracture-related and non-fracture-related complication rates were low (non-union 3 %; 1 myocardial infarction).ConclusionThis study shows that it is safe and justifiable to consider surgical treatment of a severely dislocated proximal humerus fracture in selected patients aged 75 and older.Level of evidenceAccording to OCEBM Working Group, Level IV.
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