Fracture-induced pain-like behaviours in a femoral fracture mouse model
Autor: | I F McNally, Chantal Chenu, A. Fisher, F Ter Heegde, Mark Hopkinson, Stephanie Gohin, A Billinton, R Magnusdottir, N. Upton |
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Rok vydání: | 2021 |
Předmět: |
Male
0301 basic medicine medicine.medical_specialty Ovariectomy Endocrinology Diabetes and Metabolism medicine.medical_treatment Osteoporosis Pain behaviours Pain Bone healing medicine.disease_cause Mouse model Weight-bearing Mice 03 medical and health sciences Nerve growth factor 0302 clinical medicine medicine Animals Bony Callus Reduction (orthopedic surgery) Fracture Healing business.industry Sham surgery Femoral fracture medicine.disease Disease Models Animal 030104 developmental biology Nociception Anesthesia Orthopedic surgery Original Article Female business Fractures Femoral Fractures 030217 neurology & neurosurgery |
Zdroj: | Osteoporosis International |
ISSN: | 1433-2965 0937-941X |
Popis: | Summary This study is the first comprehensive characterisation of the pain phenotype after fracture using both evoked and naturalistic behaviours in adult male and ovariectomised female mice. It also shows that an anti-nerve growth factor (NGF) therapy could be considered to reduce pain after fracture surgery. Introduction Bone fractures are common due to the ageing population and very painful even after healing. The phenotype of this pain is still poorly understood. We aimed to characterise it in a femoral fracture model in mice. Methods We employed both adult male, and female ovariectomised (OVX) mice to mimic osteoporotic fractures. Mice underwent a unilateral femoral fracture maintained by an external fixator or a sham surgery. Pain behaviours, including mechanical and thermal sensitivity, weight bearing and LABORAS, were measured from baseline to 6 weeks after fracture. The effect on pain of an antibody against nerve growth factor (anti-NGF) was assessed. Changes in nerve density at the fracture callus were analysed by immunohistochemistry. Results Following surgery, all groups exhibited high levels of invoked nociception. Mechanical and thermal hyperalgesia were observed from 1 week after surgery, with nociceptive sensitization in the fracture group maintained for the 6 weeks, whereas it resolved in the sham group after 3 weeks. OVX induced reduction in pain thresholds, which was maintained after fracture. The frequency of naturalistic behaviours did not change between groups. Anti-NGF administered before and weekly after surgery alleviated fracture-induced mechanical nociception. The density of nerve fibres in the fracture callus was similar in all groups 6 weeks after surgery. Conclusions Fractures in rodent models are highly painful in both sexes. This pain-like phenotype is prolonged and should be routinely considered in fracture healing studies as it can affect the study outcome. The anti-NGF alleviates fracture-induced mechanical pain. |
Databáze: | OpenAIRE |
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