Repeated autologous intraarticular blood injections as an animal model for joint pain in haemophilic arthropathy

Abstract

IntroductionHaemophilic arthropathy following recurrent joint bleedings is one of the major disease-related complications in people with haemophilia (PWH), leading to mostly chronic joint pain. Since many antinociceptive principles interfere with the clotting system, PWH are restricted in treatment options, thereby defining a medical need for novel therapeutic principles. However, we lack the availability of an animal model for joint pain in haemophilic arthropathy for testing these.MethodsIn this study, we aimed to validate the rat model of repeated autologous intraarticular blood injections specifically for pain-related behavior. During an observation period of 50 days, groups of animals were injected weekly into one knee joint with either whole blood or cellular/plasma components.ResultsInjections induced primary hyperalgesia starting after the third injection, accompanied by mild functional gait changes and joint swelling. Secondary hyperalgesia and quantitative gait disturbances were not observed. This phenotype was most prominent in whole blood injected animals, with effect sizes of cells and plasma being additive. In order to differentiate haemophilia-related arthropathy from traumatic joint bleeding, another group was injected with whole blood only once, which did not cause any alterations.ConclusionsRepeated autologous intraarticular injections of blood showed a time course, inflammatory response and reduction in pain thresholds similar to the signs and symptoms observed in PWH. Therefore, this model may be utilised in the future for testing novel antinociceptive principles in haemophilia-associated joint pain.

Impact of autologous whole blood administration upon experimental mouse models of acute Trypanosoma cruzi infection

“…Our data corroborate results found in another experimental model (rat) of repeated autologous intraarticular blood injection that provoked a pain-related behavior [49]. For a period of 50 days, animals were injected weekly in one knee joint with either whole blood or cellular/plasma components; the results demonstrated primary hyperalgesia starting after the third injection of whole blood samples, accompanied by mild functional gait changes [49]. The authors found that this side effect was most prominent in whole blood injected animals as compared to plasma injection and thus the effect of the cells may be additive in promoting pain.…”

“…Our findings related to behavioral parameters showed that although animals treated with one or three injections of AWB or saline showed no significant changes, in 20% (4 out of 20 mice) of those that received 20 μL for three times presented an altered paw gait. Our data corroborate results found in another experimental model (rat) of repeated autologous intraarticular blood injection that provoked a pain-related behavior [ 49 ]. For a period of 50 days, animals were injected weekly in one knee joint with either whole blood or cellular/plasma components; the results demonstrated primary hyperalgesia starting after the third injection of whole blood samples, accompanied by mild functional gait changes [ 49 ].…”

Extracellular matrix‐blood composite injection reduces post‐traumatic osteoarthritis after anterior cruciate ligament injury in the rat

“…There is also evidence of improved clinical symptoms in patients with osteoarthritis after injection of platelet rich growth factors . However, other studies reported no improvement in OA progression with PRP or whole blood injection . In addition, the combination of blood with extracellular matrix proteins has been shown to promote a prolonged release of multiple platelet‐associated growth factors …”

“…17 However, other studies reported no improvement in OA progression with PRP or whole blood injection. 18,19 In addition, the combination of blood with extracellular matrix proteins has been shown to promote a prolonged release of multiple platelet-associated growth factors. 20,21 We hypothesized that the application of the EMBC either immediately or 14 days after ACLT would reduce the histologic cartilage degeneration of the medial tibial plateau, prevent trabecular bone changes in the medial compartment and reduce the development of gait asymmetry after ACL injury in an ACL transection model.…”

O efeito do exercício aeróbico aquático na hemartrose experimental induzida em ratos

“…Estudos experimentais em camundongos knockout-FVIII e modelos wild-type, além de ratos (Boettger et al, 2013), coelhos (Ravanbod et al, 2011) e cães (Hooiveld et al, 2004) com infusão de sangue no espaço intra-articular vêm sendo utilizados na investigação do processo de destruição da articulação que ocorre na hemartrose hemofílica . Porém, estes estudos têm sido direcionados apenas para a avaliação de terapias medicamentosas.…”