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bioRxiv · 10.1101/2022.08.22.504732

No evidence for cognitive impairment in an experimental rat model of knee osteoarthritis and associated chronic pain

Goncalves, S.·Hathway, G. J.·Woodhams, S. G.·Chapman, V.·Bast, T.
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Abstract

Although chronic pain states have been associated with impaired cognitive functions, including memory and cognitive flexibility, the cognitive effects of osteoarthritis (OA) pain remain to be clarified. The aim of this study was to measure cognitive function in the mono-iodoacetate (MIA) rat model of chronic OA-like knee pain. We used young adult male Lister hooded rats, which are well suited for cognitive testing. Rats received either a unilateral knee injection of MIA (3mg/50{micro}L) or saline as control. Joint pain at rest was assessed for up to 12 weeks using weight-bearing asymmetry, and referred pain at a distal site using determination of hindpaw withdrawal thresholds (PWT). The watermaze delayed-matching-to-place (DMP) test of rapid place learning, novel object recognition (NOR) memory assay and an operant response-shift and -reversal task were used to measure memory and behavioural flexibility. Open field locomotor activity, startle response, and prepulse inhibition (PPI) were also measured for comparison. MIA-injected rats showed markedly reduced weight-bearing on the injured limb, as well as pronounced cartilage damage and synovitis, but interestingly no changes in PWT. Rearing was reduced, but otherwise locomotor activity was normal and no changes in startle and PPI were detected. MIA-injected rats had intact watermaze DMP performance, suggesting no substantial change in hippocampal function, and there were no changes in NOR memory or performance on the operant task of behavioural flexibility. Our finding that OA-like pain does not alter hippocampal function, unlike other chronic pain conditions, is consistent with human neuroimaging findings.

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Goncalves, S., Hathway, G. J., Woodhams, S. G., Chapman, V., Bast, T.. 2022-08-22. No evidence for cognitive impairment in an experimental rat model of knee osteoarthritis and associated chronic pain. https://doi.org/10.1101/2022.08.22.504732

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