Determinants for Quantitative Sensory Testing and the Association with Chronic Musculoskeletal Pain in the General Elderly Population.

OBJECTIVE: Chronic musculoskeletal pain is accompanied by central sensitization, which can be determined with quantitative sensory testing (QST). In this study, we aim to investigate whether central sensitization, as measured by thermal QST, is detectable in community-dwelling elderly individuals suffering from self-reported chronic pain and identify determinants influencing thermal QST measurement analyses and interpretation. METHODS: In 3,936 participants of the Rotterdam Study, cold and warmth sensitivity and heat pain thresholds were determined using the thermo-sensory analyzer TSA II (Medoc Advanced Medical Systems, Durham, NC, U.S.A.). Using Cox regression, associations were studied with chronic pain and potential determinants (body mass index [BMI], reaction speed, systolic and diastolic blood pressure, skin color, skin temperature, seasonal influence, depression, anxiety, atopic eczema, age at menarche, years since menopause, hormone replacement therapy (HRT) use during menopause, and reproductive lifespan). RESULTS: In addition to the effect of age and gender on thermal sensitivity, darker skin color and the presence of atopic eczema were associated with higher sensitivity for heat pain. Cold sensitivity and warmth sensitivity thresholds were both influenced by BMI, reaction speed, skin temperature, season, depression, dark skin color, years since menopause, and reproductive lifespan. The presence of chronic pain was associated with 0.2 degrees lower heat pain threshold in all participants, and 0.3 degrees lower in individuals with chronic pain in more than 2 sites. CONCLUSION: 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.

Proximal fractures of the humerus in patients older than 75 years of age: should we consider operative treatment?

BACKGROUND: Over 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 METHODS: In 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. RESULTS: Sixty-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). CONCLUSION: This 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 EVIDENCE: According to OCEBM Working Group,Level IV.

Genome-wide association study meta-analysis of chronic widespread pain: evidence for involvement of the 5p15.2 region.

BACKGROUND AND 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 1308 female CWP cases and 5791 controls of European descent, and replicated the effects of the genetic variants with suggestive evidence for association in 1480 CWP cases and 7989 controls. 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 chaperonin-containing-TCP1-complex-5 gene (CCT5) and downstream of FAM173B, was found to be associated with a 30% higher risk of CWP (minor allele frequency=43%; OR=1.30, 95% CI 1.19 to 1.42, p=1.2×10(-8)). Combined with the replication, we observed a slightly attenuated OR of 1.17 (95% CI 1.10 to 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 to 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.

Asymptomatic radiographic hip osteoarthritis is associated with gait differences, especially in women: A population-based study.

BACKGROUND: Hip and knee osteoarthritis (OA) are debilitating diseases that impair gait at severe stages. Although associations between OA and gait are established for normal walking, little is known about its relation with turning and tandem (heel-to-toe) walking. Furthermore, it is unknown how asymptomatic OA associates with gait, and whether associations differ by sex. We investigated how symptomatic and asymptomatic hip and knee OA associate with gait in community-dwelling individuals. METHODS: In 2706 participants of a population-based cohort study, gait was assessed by electronic walkway and summarised into seven gait domains. Hip and knee radiographs were graded for radiographic OA (ROA) using the Kellgren and Lawrence (K&L) score. Linear regression was used to investigate associations between ROA and gait. Analyses were repeated including only participants with asymptomatic ROA, defined as a K&L-score of 2 without pain. RESULTS: In total, 177 participants (6.5%) had hip ROA and 441 (16.3%) knee ROA. We found no associations of knee ROA with gait. Hip ROA associated with Rhythm, Tandem, and Turning. Furthermore, unilateral hip ROA associated with larger gait asymmetry and gait differences in osteoarthritic and non-osteoarthritic leg, when compared to people without hip ROA. Associations between hip ROA and gait were generally stronger for women than men. Associations for hip ROA remained after restricting to asymptomatic ROA. CONCLUSION: Hip ROA, but not knee ROA, associates with gait differences in normal walking, turning, and tandem walking in community-dwelling individuals. These associations differ between the sexes, and are already present for asymptomatic ROA.

Lower sex hormone levels are associated with more chronic musculoskeletal pain in community-dwelling elderly women.

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.

Chronic joint pain in the lower body is associated with gait differences independent from radiographic osteoarthritis.

Gait is an important indicator of health. Chronic lower body pain may impair gait and lead to morbidity and mortality. We investigated the associations between lower body pain and gait in community-dwelling individuals, independent from osteoarthritis (OA). This population based cohort study included 2304 Rotterdam Study participants who underwent electronic walkway gait assessment. Thirty different variables resulting from gait assessment were summarized into seven gait domains using principle components analysis: i.e. Rhythm, Variability, Phases, Pace, Tandem, Turning, and Base of Support. Chronic lower body pain was assessed using pain drawings. OA was defined as a Kellgren & Lawrence score of 2 or higher on radiographs of the hip and/or knee. Linear regression analysis was used to study associations. Participants with chronic pain in the leg and hip, had lower Rhythm, Phases, and Pace, independent from OA. Additionally, we found unilateral pain to associate with larger gait asymmetry. No associations were found between chronic pain and the other gait domains, including gait variability. However, within individuals with hip pain, gait variability was higher in individuals with radiographic OA compared to those without OA. This is the first population based study showing chronic lower body pain associates with gait differences independent from OA. Participants with pain were found to walk with slower and smaller steps, longer double support and more asymmetry. Proper care and treatment of chronic pain could be a way of reducing gait problems and thereby fall risk and associated mortality. In addition, gait assessment may help identifying individuals with OA from those having pain due to other causes.

Finger length pattern as a biomarker for osteoarthritis and chronic joint pain: a population-based study and meta-analysis after systematic review.

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.

Preventing enterocyte damage by maintenance of mean arterial pressure during major nonabdominal surgery in children.

Loss of the gut barrier, which is related to hypotension and gastrointestinal hypoperfusion during surgery, has been implicated as a critical event in postoperative complications development. This study aims at preventing gut barrier loss by maintenance of mean arterial pressure (MAP) in patients undergoing major nonabdominal surgery. In 20 previously included children undergoing spinal fusion surgery, the critical MAP value, which should be maintained to prevent enterocyte damage, was determined. In the following 12 children, MAP was kept above the critical value during surgery. Gut mucosal barrier loss was assessed by plasma intestinal fatty acid-binding proteins levels, a marker for enterocyte damage. Gastrointestinal perfusion was measured by gastric tonometry. First, we determined that the MAP should be maintained greater than 60 mmHg to prevent enterocyte damage. Next, maintenance of the MAP above this critical value during surgery resulted in adequate intestinal perfusion and preservation of enterocyte integrity, represented by intestinal fatty acid-binding protein levels within the reference range. This study shows that maintenance of the MAP at greater than 60 mmHg is associated with adequate intestinal perfusion and reduced enterocyte loss in children undergoing major nonabdominal surgery. These data stress the importance and benefits of good circulatory management during major surgery.