Corrigendum to "Study protocol for the follow-up examination of the Nor-Hand study: A hospital-based observational cohort study exploring pain and biomarkers in people with hand osteoarthritis" [Osteoarthr. Cartil. Open 3 (2021) 100198].

[This corrects the article DOI: 10.1016/j.ocarto.2021.100198.].

Associations between pain sensitization and measures of physical function in people with hand osteoarthritis: Results from the Nor-Hand study.

OBJECTIVE: To examine whether pain sensitization is associated with hand and lower extremity function in people with hand osteoarthritis (OA) in the Nor-Hand study. DESIGN: Pain sensitization was assessed by pressure pain thresholds (PPTs) and temporal summation (TS). Hand function was assessed by Australian/Canadian Osteoarthritis Hand Index (AUSCAN) (range: 0-36), grip strength and Moberg pick-up test, and lower extremity function was assessed by Western Ontario and McMaster Universities Osteoarthritis Index (range: 0-68), 30-s chair stand test, and 40-m walk test. We examined whether sex-standardized PPT and TS values were cross-sectionally associated with measures of physical function using linear regression analyses. Beta coefficients were presented per sex-specific standard deviation of PPT and TS. The mediating effect of pain was examined by causal-inference based mediation analysis. RESULTS: In 206 participants, higher PPTs at/near the hand, indicative of less peripheral and/or central pain sensitization, were associated with greater grip strength and better self-reported hand function (beta for PPT at finger joint on AUSCAN function: -1.41, 95% CI -2.40, -0.42). Higher PPTs at/near the hand, near the knee and at trapezius were associated with lower extremity function, although not statistically significant for all outcomes. Self-reported pain severity mediated the effect of PPT on self-reported function. TS was not associated with hand or lower extremity function. CONCLUSION: Peripheral sensitization, and possibly central sensitization, was associated with impaired function. Effects of PPTs on self-reported function were mediated by self-reported pain, whereas there might be a direct effect of sensitization or effects through other mediators on performance-based function.

Associations of Body Mass Index With Pain and the Mediating Role of Inflammatory Biomarkers in People With Hand Osteoarthritis.

OBJECTIVE: To examine the association of body mass index (BMI) with pain in people with hand osteoarthritis (OA), and explore whether this association, if causal, is mediated by systemic inflammatory biomarkers. METHODS: In 281 Nor-Hand study participants, we estimated associations between BMI and hand pain, as measured by the Australian/Canadian Osteoarthritis Hand Index (AUSCAN; range 0-20) and Numerical Rating Scale (NRS; range 0-10); foot pain, as measured by NRS (range 0-10); knee/hip pain, as measured by the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC; range 0-20); painful total body joint count; and pain sensitization. We fit natural-effects models to estimate natural direct and natural indirect effects of BMI on pain through inflammatory biomarkers. RESULTS: Each 5-unit increase in BMI was associated with more severe hand pain (on average increased AUSCAN by 0.64 [95% confidence interval (95% CI) 0.23, 1.08]), foot pain (on average increased NRS by 0.65 [95% CI 0.36, 0.92]), knee/hip pain (on average increased WOMAC by 1.31 [95% CI 0.87, 1.73]), generalized pain, and pain sensitization. Mediation analyses suggested that the effects of BMI on hand pain and painful total body joint count were partially mediated by leptin and high-sensitivity C-reactive protein (hsCRP), respectively. Effect sizes for mediation by leptin were larger for the hands than for the lower extremities, and were statistically significant for the hands only. CONCLUSION: In people with hand OA, higher BMI is associated with greater pain severity in the hands, feet, and knees/hips. Systemic effects of obesity, measured by leptin, may play a larger mediating role for pain in the hands than in the lower extremities. Low-grade inflammation, measured by hsCRP, may contribute to generalized pain in overweight/obese individuals.

Associations of pain sensitisation with tender and painful joint counts in people with hand osteoarthritis: results from the Nor-Hand study.

OBJECTIVE: To examine associations of pain sensitisation with tender and painful joint counts and presence of widespread pain in people with hand osteoarthritis (OA). METHODS: Pressure pain thresholds (PPT) at a painful finger joint and the tibialis anterior muscle, and temporal summation (TS) were measured in 291 persons with hand OA. We examined whether sex-standardised PPT and TS values were associated with assessor-reported tender hand joint count, self-reported painful hand and total body joint counts and presence of widespread pain using linear and logistic regression analyses adjusted for age, sex, body mass index, education and OA severity. RESULTS: People with lower PPTs at the painful finger joint (measure of peripheral and/or central sensitisation) had more tender and painful hand joints than people with higher PPTs. PPT at tibialis anterior (measure of central sensitisation) was associated with painful total body joint count (beta=-0.82, 95% CI -1.28 to -0.35) and presence of widespread pain (OR=0.57, 95% CI 0.43 to 0.77). The associations between TS (measure of central sensitisation) and joint counts in the hands and the total body were statistically non-significant. CONCLUSION: This cross-sectional study suggested that pain sensitisation (ie, lower PPTs) was associated with joint counts and widespread pain in hand OA. This knowledge may be used for improved pain phenotyping of people with hand OA, which may contribute to better pain management through more personalised medicine. Further studies are needed to assess whether a reduction of pain sensitisation leads to a decrease in tender and painful joint counts.

Associations between joint pathologies and central sensitization in persons with hand osteoarthritis: results from the Nor-Hand study.

OBJECTIVE: Pain sensitization is associated with pain severity in persons with hand OA. What contributes to pain sensitization is unclear. This study explores whether hand OA pathologies and symptom duration are related to central sensitization. METHOD: Participants with hand OA in the Nor-Hand study underwent bilateral hand radiography and US examination. Central sensitization was assessed with pressure pain thresholds (PPT) at remote sites (wrist, trapezius and tibialis anterior muscles) and temporal summation. We examined whether hand OA pathologies, independent of each other, including structural severity (Kellgren-Lawrence sum score, presence of erosive hand OA), inflammatory severity (greyscale synovitis and power Doppler activity sum scores) and symptom duration, were related to central sensitization, adjusting for age, sex, BMI, comorbidities and OA-severity of knee/hip. RESULTS: In 291 participants (88% women, median age 61 years, interquartile range 57-66 years) Kellgren-Lawrence, greyscale synovitis and power Doppler activity sum scores were not associated with lower PPTs at remote sites. Persons with erosive hand OA had lower PPTs at the wrist (adjusted beta -0.75, 95% CI -1.32, -0.19) and tibialis anterior (adjusted beta -0.82, 95% CI -1.54, -0.09) and had greater temporal summation (adjusted beta 0.56, 95% CI 0.12, 1.01) compared with persons with non-erosive disease. No associations were found for symptom duration. CONCLUSIONS: A person's overall amount of structural or inflammatory hand OA pathologies was not associated with central sensitization. Although persons with erosive hand OA showed greater signs of central sensitization, the small differences suggest that central sensitization is mainly explained by factors other than joint pathologies.

Study protocol for the follow-up examination of the Nor-Hand study: A hospital-based observational cohort study exploring pain and biomarkers in people with hand osteoarthritis.

Objective: This study aims to increase the understanding of pain mechanisms in hand OA and explore potential risk factors for pain development or worsening in a biopsychosocial framework. Another important aim is to validate potential soluble and imaging OA biomarkers. Design: The follow-up examination of the Nor-Hand hospital-based observational cohort study started in October 2019 and was completed in May 2021. In total, 212 of the 300 participants with hand OA who were examined at baseline attended the follow-up study. The participants underwent clinical joint examinations, medical and functional assessments, quantitative sensory testing, fluorescence optical imaging, ultrasound of the hands, acromioclavicular joints, feet, knees and hips, conventional radiographs of the hands and feet and magnetic resonance imaging of the dominant hand. Blood and urine samples were collected, and all participants answered questions about demographic factors and OA-related questionnaires. Associations between disease variables and symptoms will be examined in cross-sectional and longitudinal analyses. Longitudinal analyses will be performed to assess the predictive value of baseline variables on hand OA outcomes. Conclusion: Current knowledge about predictors for disease progression in hand OA is limited, but with longitudinal data we will be able to explore the predictive value of baseline variables on hand OA outcomes, such as changes in patient-reported outcomes or changes in soluble and imaging biomarkers. This provides a unique opportunity to gain more knowledge about the natural disease course of hand OA.

Associations Between Radiographic and Ultrasound-Detected Features in Hand Osteoarthritis and Local Pressure Pain Thresholds.

OBJECTIVE: Pain sensitization contributes to the complex osteoarthritis (OA) pain experience. The relationship between imaging features of hand OA and clinically assessed pain sensitization is largely unexplored. This study was undertaken to examine the association of structural and inflammatory features of hand OA with local pressure pain thresholds (PPTs) in the Nor-Hand study. METHODS: The cross-sectional relationship of severity of structural radiographic features of hand OA (measured according to the Kellgren/Lawrence scale [grade 0-4] and the absence or presence of erosive joint disease) as well as ultrasound-detected hand joint inflammation (assessed by gray-scale synovitis [grade 0-3] and the absence or presence of power Doppler activity) to the PPTs of 2 finger joints was examined by multilevel regression analyses adjusted for age, sex, and body mass index, using beta values with 95% confidence intervals (95% CIs). RESULTS: A total of 570 joints in 285 participants included in the Nor-Hand study were assessed. Greater structural and inflammatory severity was associated with lower PPTs, with adjusted beta values of -0.5 (95% CI -0.6, -0.4) per Kellgren/Lawrence grade increase, -1.4 (95% CI -1.8, -0.9) for erosive versus non-erosive joints, -0.7 (95% CI -0.9, -0.6) per gray-scale synovitis grade increase, and -1.5 (95% CI -1.8, -1.1) for joints with power Doppler activity on ultrasound versus those without. CONCLUSION: Greater severity of structural pathologic features and hand joint inflammation was associated with lower PPTs in the finger joints of patients with hand OA, indicating pain sensitization. Our results indicate that pain sensitization might be driven by structural and inflammatory pathology in hand OA.

Validation of the Intermittent and Constant Osteoarthritis Pain Questionnaire in Patients with Hand Osteoarthritis: Results from the Nor-Hand Study.

OBJECTIVE: To examine the validity of a modified Intermittent and Constant Osteoarthritis Pain (ICOAP) questionnaire for assessment of pain in hand osteoarthritis (OA). METHODS: The modified ICOAP-hand questionnaire was administered to 300 patients [89% female, median (interquartile range) age: 61 (57-66) yrs] in the Nor-Hand observational cohort study. The questionnaire was completed twice by 31 patients and test-retest reliability was assessed by intraclass correlation coefficients (ICC) for sum scores and weighted κ scores for individual items. Internal consistency was assessed by Cronbach's alpha coefficient and item-total correlations. Correlations between the ICOAP-hand questionnaire, the Australian/Canadian Hand OA Index (AUSCAN) hand pain subscale, and pain on a numerical rating scale (NRS) were analyzed using Spearman correlation analyses. RESULTS: We found a substantial overlap between constant and intermittent pain (46% reporting constant + intermittent pain and 33% reporting no pain). Test-retest reliability analysis of ICOAP-hand showed an ICC of 0.89 for the total scale and weighted κ values between 0.39-0.70 for the individual items. Principal component analysis revealed one component with an eigenvalue of 7.9, explaining 72% of the total variance. Cronbach's alpha coefficient values > 0.93 and strong item-total correlations proved high internal consistency. ICOAP-hand was strongly correlated with NRS hand pain and the AUSCAN pain subscale. CONCLUSION: ICOAP-hand is a reliable pain index that correlates with other available pain questionnaires. However, our results indicate that constant and intermittent pain do not represent separate constructs in hand OA, questioning the usefulness of the 2 subscales. [ClinicalTrials.gov: NCT03083548].

Peripheral and Central Sensitization of Pain in Individuals With Hand Osteoarthritis and Associations With Self-Reported Pain Severity.

OBJECTIVE: Pain sensitization, an important osteoarthritis (OA) pain mechanism, has not been substantially investigated in patients with hand OA. It is unknown how peripheral and central sensitization are related to self-reported hand pain. METHODS: Individuals with verified hand OA in the Nor-Hand study underwent quantitative sensory testing of pressure pain thresholds (PPTs) locally (painful and nonpainful finger joints) and remotely (wrist, trapezius, and tibialis anterior muscles), and testing of temporal summation (TS), a manifestation of central sensitization. We examined cross-sectional associations of PPT tertiles and TS with hand pain using the Numerical Rating Scale (NRS) (range 0-10) and the Australian/Canadian Osteoarthritis Hand Index (AUSCAN) pain subscale (range 0-20). Linear regression models were adjusted for demographics, psychosocial factors, and radiographic severity. RESULTS: This study included 282 participants (88% female) with a median age of 61 years (interquartile range [IQR] 57-66). Participants with the lowest PPTs in their finger joints and in most remote locations reported higher NRS pain values, compared to patients with the highest PPTs, with adjusted ß values ranging from 0.6 (95% confidence interval [95% CI] 0.0, 1.2) to 0.9 (95% CI 0.3, 1.5). The 118 participants (42%) with TS reported higher mean ± SD NRS pain values compared to those without TS (4.1 ± 2.4 versus 3.1 ± 1.7; adjusted ß = 0.6 [95% CI 0.2, 1.1]). Neither PPTs nor the presence of TS were associated with AUSCAN pain. CONCLUSION: Central sensitization was common in patients with hand OA. Lower local and widespread PPTs and the presence of TS were associated with higher hand pain intensity, even after adjustment for demographics, psychosocial factors, and radiographic severity. Sensitization may therefore represent a possible treatment target.