Quantitation OF ARGS aggrecan fragments in synovial fluid, serum and urine from osteoarthritis patients.

OBJECTIVE: To characterise ARGS neoepitope concentrations in various matrices from patients with knee osteoarthritis (OA) and assess performance of an immunoassay to facilitate clinical development of therapeutics affecting the A disintegrin and metalloproteinase with thrombospondin motifs 5 (ADAMTS-5) pathway. DESIGN: Matched sera, urine, and synovial fluid (SF) (surgical subjects only) were collected from healthy subjects, subjects with knee OA (non-surgical OA), and OA subjects undergoing total knee replacement (OA-TKR; n = 20 per group). Diurnal and inter-day variation was evaluated in the non-surgical OA group over 3 separate visits. Serum and urine samples were collected on two visits for the OA-TKR group with SF taken only at the time of surgery. ARGS neoepitope was quantitated using an optimized immunoassay. RESULTS: Serum ARGS neoepitope concentrations were elevated in OA-TKR subjects compared to non-surgical OA subjects (P = 0.005) and healthy subjects (P = 0.0002). Creatinine corrected urinary ARGS neoepitope concentrations were more variable, but were also elevated in the OA-TKR subjects compared to healthy subjects (P = 0.008). No significant diurnal effect or inter-day variance was observed in serum or urine. Serum ARGS neoepitope concentrations correlated with age (P = 0.0252) but not with total number of joints with OA involvement. SF ARGS neoepitope concentrations correlated with Western Ontario and MacMaster OA Index (WOMAC) stiffness score (P = 0.04) whereas a weaker, non-significant trend towards positive correlation with combined WOMAC score and the number of concurrent joints was observed. CONCLUSIONS: This study utilized a sensitive and robust assay to evaluate ARGS neoepitope concentrations in various matrices in OA patients and healthy volunteers. ARGS neoepitope appears promising as a prognostic/stratification marker to facilitate patient selection and as an early pharmacodynamic marker for OA therapeutic trials.

Arthritic pain is processed in brain areas concerned with emotions and fear.

OBJECTIVE: Functional neuroimaging studies have shown that experimentally induced acute pain is processed within at least 2 parallel networks of brain structures collectively known as the pain matrix. The relevance of this finding to clinical pain is not known, because no direct comparisons of experimental and clinical pain have been performed in the same group of patients. The aim of this study was to compare directly the brain areas involved in processing arthritic pain and experimental pain in a group of patients with osteoarthritis (OA). METHODS: Twelve patients with knee OA underwent positron emission tomography of the brain, using (18)F-fluorodeoxyglucose (FDG). Scanning was performed during 3 different pain states: arthritic knee pain, experimental knee pain, and pain-free. Significant differences in the neuronal uptake of FDG between different pain states were investigated using statistical parametric mapping software. RESULTS: Both pain conditions activated the pain matrix, but arthritic pain was associated with increased activity in the cingulate cortex, the thalamus, and the amygdala; these areas are involved in the processing of fear, emotions, and in aversive conditioning. CONCLUSION: Our results suggest that studies of experimental pain provide a relevant but quantitatively incomplete picture of brain activity during arthritic pain. The search for new analgesics for arthritis that act on the brain should focus on drugs that modify this circuitry.

Acoustic noise in functional magnetic resonance imaging reduces pain unpleasantness ratings.

Functional magnetic resonance imaging (fMRI) is increasingly used in cognitive studies. Unfortunately, the scanner produces acoustic noise during the image acquisition process. Interference from acoustic noise is known to affect auditory, visual and motor processing, raising the possibility that acoustic interference may also modulate processing of other sensory modalities such as pain. With the increasing use of fMRI in the investigation of the mechanisms of pain perception, particularly in relation to attention, this issue has become highly relevant. Pain is a complex experience, composed of sensory-discriminative, affective-motivational and cognitive-evaluative components. The aim of this experiment was to assess the effect of MRI scanner noise, compared to white noise, on the affective (unpleasantness) and the sensory-discriminative (localisation) components of pain. Painful radiant heat from a CO(2) laser was delivered to the skin of the right forearm in 24 healthy volunteers. The volunteers attended to either pain location or pain unpleasantness during three conditions: i) no noise, ii) exposure to MRI scanner noise (85 dB) or iii) exposure to white noise (85 dB). Both MRI scanner noise and white noise significantly reduced unpleasantness ratings (from 5.1 +/- 1.6 in the control condition to 4.7 +/- 1.5 (P = 0.002) and 4.6 +/- 1.6 (P < 0.001) with scanner and white noise respectively), whereas the ability to localise pain was not significantly affected (from 85.4 +/- 9.2% correct in the control condition to 83.1 +/- 10.3% (P = 0.06) and 83.9 +/- 9.5% (P = 0.27) with MRI scanner and white noise respectively). This phenomenon should be taken into account in the design of fMRI studies into human pain perception.