Abiola Harrison

Use of the painDETECT tool in rheumatoid arthritis suggests neuropathic and sensitization components in pain reporting

Rheumatoid arthritis (RA) is an inflammatory autoimmune condition typified by systemic inflammation targeted toward synovial joints. Inhibition of proinflammatory networks by disease-modifying antirheumatic drugs, eg, methotrexate and biologic therapies, including tumor necrosis factor-α inhibitors, often leads to suppression of disease activity observed at the clinical level. However, despite the era of widespread use of disease-modifying treatments, there remain significant groups of patients who continue to experience pain. Our study formulated a pain assessment tool in the arthritis clinic to assess feasibility of measurements including the visual analog scale (VAS) and painDETECT to assess multimodal features of pain in people with established RA (n=100). Clinical measures of disease activity (Disease Activity Score in 28 Joints [DAS28]) were also recorded. Our data showed that despite the majority of subjects on at least one disease-modifying agent, the majority of patients reported severe pain (54%) by VAS, despite well-controlled clinical disease, with mean DAS28 2.07±0.9. Using the painDETECT questionnaire, 67% of patients had unlikely neuropathic pain. A significant proportion of subjects (28%) had possible neuropathic pain and 5% had features of likely neuropathic pain by painDETECT scoring. We found a positive correlation between VAS and painDETECT (R2=0.757). Of note, the group who had likely or probable neuropathic pain also showed significantly increased pain reporting by VAS (P<0.01). Subjects who were clinically obese (body mass index >30) also had statistically higher proportions of pain reporting (VAS 89.0±0.7 mm) compared with subjects who had a normal body mass index (VAS 45.2±21.8 mm), P<0.05. Our findings suggest that multimodal features of pain perception exist in RA, including neuropathic and sensitization elements, perhaps explaining why a subgroup of people with RA continue to experience ongoing pain, despite their apparent suppression of inflammation.

Microarray analysis of bone marrow lesions in osteoarthritis demonstrates upregulation of genes implicated in osteochondral turnover, neurogenesis and inflammation

Objective Bone marrow lesions (BMLs) are well described in osteoarthritis (OA) using MRI and are associated with pain, but little is known about their pathological characteristics and gene expression. We evaluated BMLs using novel tissue analysis tools to gain a deeper understanding of their cellular and molecular expression. Methods We recruited 98 participants, 72 with advanced OA requiring total knee replacement (TKR), 12 with mild OA and 14 non-OA controls. Participants were assessed for pain (using Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC)) and with a knee MRI (using MOAKS). Tissue was then harvested at TKR for BML analysis using histology and tissue microarray. Results The mean (SD) WOMAC pain scores were significantly increased in advanced OA 59.4 (21.3) and mild OA 30.9 (20.3) compared with controls 0.5 (1.28) (p<0.0001). MOAKS showed all TKR tissue analysed had BMLs, and within these lesions, bone marrow volume was starkly reduced being replaced by dense fibrous connective tissue, new blood vessels, hyaline cartilage and fibrocartilage. Microarray comparing OA BML and normal bone found a significant difference in expression of 218 genes (p<0.05). The most upregulated genes included stathmin 2, thrombospondin 4, matrix metalloproteinase 13 and Wnt/Notch/catenin/chemokine signalling molecules that are known to constitute neuronal, osteogenic and chondrogenic pathways. Conclusion Our study is the first to employ detailed histological analysis and microarray techniques to investigate knee OA BMLs. BMLs demonstrated areas of high metabolic activity expressing pain sensitisation, neuronal, extracellular matrix and proinflammatory signalling genes that may explain their strong association with pain.

The effect of pregabalin or duloxetine on arthritis pain: a clinical and mechanistic study in people with hand osteoarthritis [Corrigendum]

[This corrects the article on p. 2437 in vol. 10, PMID: 29066930.].

The effect of pregabalin or duloxetine on arthritis pain

Osteoarthritis (OA) is the most prevalent arthritis worldwide and is characterized by chronic pain and impaired physical function. We hypothesized that heightened pain in hand OA could be reduced with duloxetine or pregabalin. In this prospective, randomized clinical study, we recruited 65 participants, aged 40–75 years, with a Numerical Rating Scale (NRS) for pain of at least 5. Participants were randomized to one of the following three groups: duloxetine, pregabalin, and placebo. The primary endpoint was the NRS pain score, and the secondary endpoints included the Australian and Canadian Hand Osteoarthritis Index (AUSCAN) pain, stiffness, and function scores and quantitative sensory testing by pain pressure algometry. After 13 weeks, compared to placebo, ANOVA found significant differences between the three groups (P=0.0078). In the intention-to-treat analysis, the pregabalin group showed improvement for NRS pain (P=0.023), AUSCAN pain (P=0.008), and AUSCAN function (P=0.009), but no difference between duloxetine and placebo (P>0.05) was observed. In the per protocol analysis, NRS pain was reduced for pregabalin (P<0.0001) and duloxetine (P=0.029) compared to placebo. We conclude that centrally acting analgesics improve pain outcomes in people with hand arthritis, offering new treatment paradigms for OA pain.

FRI0556 Automated scoring of knee osteoarthritis (OA) on routine radiographs identifies disease severity in oa

Background Knee osteoarthritis (OA) causes pain and limited function of the knee, linked to cartilage loss, bone remodelling and inflammation1. Objectives We aimed to find out whether joint space measures can stratify patients into mild and advanced OA using an automated scoring tool2. Methods 86 weight-bearing radiographs (target joint: 41 left, 45 right knee) were analysed by using ImageBiopsy Lab software (JSx). Automated joint space (JS) measures were joint space width (JSW), minimum height (minH) and joint space area/region of interest (JSA/ROI, in mm2). JS measures were compared against Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) of pain, stiffness and function, with each subscale score normalised to a total score of 100. Body-mass index (BMI) and age data were available as potential covariates. Image analysis was initiated with landmarks automatically placed on the end of tibial plateau for each compartment, with fine manual adjustment of landmarks and contour spline if necessary. Clinical scores were compared between mild OA (n=24) and advanced OA (n=62); patient groups were defined according to their clinical pathway of standard care: medical management for early OA and knee replacement for advanced OA. SPSS Statistics 25 was used for analysis. An independent-samples t-test was used to compare the automated radiological and clinical scores between the groups of different OA severity. Subsequently the General Linear Model (GLM) was used to evaluate group differences with appropriate co-variates and fixed factors. Results Joint space measures were strongly linked to the two clinical groups of OA severity (mild and advanced OA). Differences were significant in the medial JSA/ROI (p<0.001), medial JSW (p=0.001), medial MinH (p<0.001), WOMAC pain (p=0.001), stiffness and function (both p=0.003). Age (p=0.014) and BMI (p=0.019) were also different between the two groups of OA severity in the t-test, and were then used as co-variates in the GLM analysis along with gender and ethnicity as fixed factors. Medial JSA/ROI (p=0.027) and medial MinH (p=0.041) were still significantly different between mild and advanced OA in the multivariate test. Receiving Operating Characteristic (ROC) curves showed that medial JSA/ROI was the better discriminator for severity of OA (AUC=0.738) when compared to WOMAC scores (AUC=0.719 for WOMAC pain).Abstract FRI0556 – Figure 1 Boxplots showing the relationship between stage of OA (mild and advanced) and (A) medial JSA/ROI, (B) lateral JSA/ROI Conclusions Medial joint space measures are possible markers for identifying the stage of disease if only radiographs were used. In particular, medial JSA/ROI may be utilised as an automated tool for characterising patient severity. References [1] Kuttapitiya A, Assi L, Laing K, et al. Microarray analysis of bone marrow lesions in osteoarthritis demonstrates upregulation of genes implicated in osteochondral turnover, neurogenesis and inflammation. Annals of the Rheumatic Diseases2017;76(10):1764–1773. [2] Hunter D, Altman R, Cicuttini F, et al. OARSI Clinical Trials Recommendations: Knee imaging in clinical trials in osteoarthritis. Osteoarthritis and Cartilage2015;23(5):698–715. Acknowledgements The software for analysis in this study was provided by ImageBiopsy Lab and all analyses were performed independently at St George’s, University of London. Disclosure of Interest None declared