A Model of Metastatic Bone Cancer Pain in the Lumbar Spine

Abstract

Introduction Bone is the third most common site for metastasis representing a poor prognosis in patients with cancer. Metastases to the spine are a common source of pain. Its secondary effects such as fractures, hypercalcemia, and neurological deficits significantly reduce patient's quality of life. Microfractures occur in metastatic regions of cancerous bone that can no longer handle ordinary loading, causing deformation of the spine and impingement of nerves. As the disease progresses, pain severity increases and it becomes more difficult to treat, causing further decrease in the quality of life of the patients. A key obstacle in the study of this disease is the lack of reliable, practical, and reproducible animal models to study spine metastatic pain. Materials and Methods Behavioral evaluation was conducted in a group of 30 athymic rats: 10 tumor-implanted (human mammary adenocarcinoma, L5 vertebral body); 10 sham (surgery performed, no tumor implanted), and 10 control rats (nontumor or surgery). Randall–Selitto and pincher tests were used to evaluate the nociceptive response in rats. Tumor growth was monitored by bioluminescent imaging (BLI) and CT. Results The mechanic nociceptive response was significantly reduced (day 45) in time and pressure applied in tumor rats compared with control or sham; a slight nonsignificant reduction was observed in the paw withdrawal in tumor-implanted rats. BLI revealed severe tumor invasion in the lower spine that was qualitatively related with lytic lesions in two or three vertebral bodies. These lesions were characterized by a decrease in the density of the bone in lumbar spine consistent with tumor location on bioluminescence. There was near-complete ablation of the posterior elements of the spine. Locomotion gait analysis showed a disruption in the normal pattern of the rat's gait. Conclusions Our intraspinal metastatic tumor model animals showed locomotor and sensory signs that are in accordance with some of the clinical manifestations in humans. These signs included a locomotor deficit and an increase in noxious sensation. Our model offers a reliable method to evaluate alternative approaches to treat pain in patients with metastatic spine disease.