Background Osteoarthritis (OA) is a degenerative joint disease affecting around 8 million people in the UK. Pain is a prominent and often disabling feature of OA, the relationship between pain and histopathological features of OA are poorly understood. Currently, there are no reparative or disease-modifying treatments for OA and thus many patients will undergo joint replacement surgery for pain relief.
Objectives To explore the effect for intra-articular mesenchymal stem cells (MSC) treatment on pain behaviour in a rodent surgical model of OA.
Methods Under isoflurane anaesthesia (1.5L/min O2, 2.5% isoflurane) joint pathology was induced in adult male Sprague Dawley Rats (160-200g) by transecting the medial collateral ligament and making a full thickness cut through the meniscus (day 0) of the left knee (Mapp et al., 2008). Baseline pain behaviour were taken immediately prior to surgery (day 0) and then from 3 until 42 days post-surgery. Pain measures were weight bearing asymmetry, assessed using an incapacitance tester, and the lowering of hindpaw mechanical withdrawal thresholds, quantified using von Frey monofilaments (1-15 g). 14 days post-surgery, rats were stratified according to behavioural pain responses and under brief isoflurane anaesthesia (3% 1L/min O2), received an intra-articular injection (through the infrapatellar ligament of the left knee) 50μl of 1.5x106 mesenchymal stem cells (n=7 rats) or serum free media (SFM; n=4 rats). Pain behaviour was quantified for a further four weeks post intra-articular injection and then the experiment was terminated. Data are expressed as mean weight bearing % (weight on ipsilateral paw – weight on contralateral paw/total weight on hindpaws) x 100% ± SEM. Statistical analysis between groups was performed using a Mann Whitney test.
Results Consistent with previous studies, from 3 days following medial meniscal transection (MNX) surgery rats exhibited increased weight bearing asymmetry and decreased ipsilateral paw withdrawal thresholds, compared to pre-surgery values. MNX rats which received the control treatment (intra-articular injection of SFM) exhibited a gradual increase in pain behaviour up to day 42. Intra-articular injection of MSCs at day 14 prevented a further increase in weight bearing asymmetry, which was significant when compared to OA rats treated with SFM, up to day 42 (weight bearing % SFM =19.5±0.6, MSC =9.5±3.5; p<0.05). MSC treatment had no effect on the hindpaw mechanical withdrawal thresholds in MNX treated rats.
Conclusions Intra-articular injection of MSCs attenuated the further development of weight bearing asymmetry in rats with established joint pathology in the MNX model of OA. There was no effect of this treatment on the development of hindpaw mechanical withdrawal thresholds. These data suggest that intra-articular injection of MSCs may alter peripherally-driven pain, but may not affect centrally-mediated pain responses in established OA.
Mapp PI, Avery PS, McWilliams DF, Bowyer J, Day C, Moores S, Webster R, Walsh DA (2008). Angiogenesis in two animal models of osteoarthritis. Osteoarthritis Cartilage 16(1): 61-69
Acknowledgements This work was funded by EPSRC and ARUK
Disclosure of Interest None declared
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