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Highly Predictive Objective Measurement of OA Joint Pain in Rat Using Bioseb Automated Dynamic Weight Bearing System
Author(s) -
Rashid Harun,
Cornicelli Joe,
Young Alan,
Samadfam Rana
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.812.3
Subject(s) - osteoarthritis , weight bearing , celecoxib , medicine , joint pain , tramadol , nociception , hindlimb , repeated measures design , morphine , body weight , reflex , anesthesia , physical medicine and rehabilitation , analgesic , physical therapy , surgery , mathematics , pathology , statistics , alternative medicine , receptor
Background Osteoarthritis (OA) is often associated with chronic debilitating joint pain. Similar pain has been reported in animal models of OA. However, most pain measuring techniques in animal are subjective in nature where reflex responses upon stimulation with nociceptive stimuli are measured. The purpose of the present study is to provide a highly reproducible objective joint pain measuring technique in the mono‐iodoacetate (MIA)‐induced OA model in rats. Methods Joint pain is induced in rat by a single intra‐articular injection of MIA (3mg/25uL) into the right knee joint. Dynamic weight bearing (DWB) patterns by different limbs and tail in the rats are quantified using the BioSeb automated DWB system. The system consists of an arena box with a pressure‐sensitive sensor mat on the bottom and an attached high‐resolution camera on the top. The rat can move freely inside the arena box. A two‐minute recording is done for each rat. Analysis of dynamic weight bearing data is done off‐line using the BioSeb software. The system automatically calculates the weight borne by each limb and the tail. DWB data are calculated by normalizing as percent of total body weight borne by each limb and tail. Joint pain is indicated by reduction in weight bearing by the MIA‐injected right hind limb. Effects of tramadol, dexamethasone, morphine, naproxen and celecoxib on MIA‐induced joint pain were evaluated at different time points post MIA injection. Results Baseline DWB data were assessed across a number of studies and very consistent and reproducible baseline weight bearing pattern was observed. The deficit in weight bearing by the MIA‐injected right hind limb was mostly compensated by extra weight bearing in left hind limb although a smaller portion was also compensated by the right front limb. Weight bearing assessment over a period of four weeks showed that MIA‐induced OA joint pain was often more intense during the first few days post MIA injection, which might be due to the acute inflammation of the joint synovium, and pain is also intense in later time points during the third and fourth week, which might be due to the cartilage damage. Of the various standard of care OA pain relieving agents examined in this model, morphine, tramadol and dexamethasone were effective in both early and late phase of the model while naproxen and celecoxib were effective only during the early phase. Conclusion Overall, the current results suggest that Bioseb dynamic weight system is reliable for objective measurement of OA joint pain in rats. Moreover, results from the validation studies with standard of care OA pain relieving agents also support the biphasic nature of the MIA‐induced OA joint pain whereby the early phase is more sensitive to NSAIDs than the later phase(s).