We performed longitudinal behavioral readouts of pain and resting-state fMRI in a mouse model of chronic pain from breast cancer derived tibial bone metastases. The developmental trajectory of behavioral readouts was used to model the fMRI response to extract pain-specific functional connectivity changes during development of a chronic pain state. The specificity of these functional readouts was supported through inhibition of osteolytic activity, reducing the nociceptive input. Thereby, characteristic functional changes could be reduced and in some regions prevented. These results emphasize the specificity of the functional readouts for developing chronic pain and could be used to evaluate novel treatments.