What Did We Learn About Fracture Pain from Animal Models?

Progress in bone fracture repair research has been made possible due to the development of reproducible models of fracture in rodents with more clinically relevant fracture fixation, where there is considerably better assessment of the factors that affect fracture healing and/or novel therapeutics. However, chronic or persistent pain is one of the worst, longest-lasting and most difficult symptoms to manage after fracture repair, and an ongoing challenge remains for animal welfare as limited information exists regarding pain scoring and management in these rodent fracture models. This failure of adequate pre-clinical pain assessment following osteotomy in the rodent population may not only subject the animal to severe pain states but may also affect the outcome of the bone healing study. Animal models to study pain were also mainly developed in rodents, and there is increasing validation of fracture and pain models to quantitatively evaluate fracture pain and to study the factors that generate and maintain fracture pain and develop new therapies for treating fracture pain. This review aims to discuss the different animal models for fracture pain research and characterize what can be learned from using animal models of fracture regarding behavioral pain states and new molecular targets for future management of these behaviors.