Wheel running, but not home cage activity in Digital Ventilated Cages® is impaired in a mouse model of breast cancer-induced bone pain

Abstract

Introduction: Cancer-induced bone pain (CIBP) due to metastatic breast cancer is common and debilitating. Effective, long-term treatment options have side effects that reduce patients' quality of life. Preclinical models are a valuable tool to test novel analgesics, but new methods that are translationally and clinically relevant are necessary. This study aimed to assess spontaneous pain-like behaviour of home cage activity and wheel running in Digital Ventilated Cages®. Method: Twenty BALB/cAnNHsd mice were housed in Digital Ventilated Cages®from Tecniplast®with GYM500 home cage running wheels. Mice were assessed by limb use analysis and static weight bearing to determine the development of CIBP and this was compared to the dark-phase home cage activity and wheel running in the Digital Ventilated Cages®. Ten mice underwent 4T1-Luc2 mammary gland adenocarcinoma cell inoculation into the right femur to establish CIBP and another ten mice underwent a sham surgical procedure. Results: The 4T1-inoculated mice displayed pain-like behaviour in limb use and weight bearing tests, demonstrating a preference for the contralateral limb. The limb use scores were compared with home cage activity and wheel running. A reduced wheel running distance corresponded to reduced limb use scores, with the shortest wheel running distances corresponding to the lowest limb use scores. However, this behavioural pattern was not observed in home cage activity, which remained consistent over the study period. Discussion: Reduced wheel running corresponded with reduced limb use scores. This suggests that wheel running behaviour is affected by the development of metastatic breast cancer. However, the home cage activity was not influenced by disease development. Digital Ventilated Cage®wheel running may be a useful behavioural assessment of spontaneous pain-like behaviour of CIBP and may be useful to assess analgesic efficacy.