Wheel Running in Digital Ventilated Cages^® Is Impaired in a Model of Cancer-induced Bone Pain

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 valuable tools for testing novel analgesics, but new methods that are translationally and clinically relevant are necessary. This study aimed to assess spontaneous pain-like behavior of home cage activity and wheel running in Digital Ventilated Cages^®.

Twenty BALB/cAnNHsd mice were housed in Digital Ventilated Cages^® from Tecniplast^® with GYM500 home cage running wheels. Ten mice underwent 4T1-Luc2 mammary gland adenocarcinoma cell inoculation into the right femur to establish CIBP and another ten mice underwent a sham procedure. Mice were assessed by limb use 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^®.

The 4T1-Luc2-inoculated mice displayed pain-like behavior 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. Reduced wheel running distance corresponded to reduced limb-use scores, with the shortest wheel running distances corresponding to the lowest scores. However, this behavioral pattern was not observed in home-cage activity, which remained consistent throughout the study.

Wheel running behavior appears to be affected by the development of metastatic breast cancer. Wheel running in a Digital Ventilated Cage^® may be a useful behavioral assessment of spontaneous pain-like behavior of CIBP and may be useful to assess analgesic efficacy.