Abstract
The majority of patients with terminal breast cancer show signs of bone metastasis, the most common cause of pain in cancer. Clinically available drug treatment options for the relief of cancer-associated bone pain are limited due to either inadequate pain relief and/or dose-limiting side-effects. One of the major hurdles in understanding the mechanism by which breast cancer causes pain after metastasis to the bones is the lack of suitable preclinical models. Until the late twentieth century, all animal models of cancer induced bone pain involved systemic injection of cancer cells into animals, which caused severe deterioration of animal health due to widespread metastasis. In this mini-review we have discussed details of a recently developed and highly efficient preclinical model of breast cancer induced bone pain: Walker 256 cancer cell- induced bone pain in rats. The model involves direct localized injection of cancer cells into a single tibia in rats, which avoids widespread metastasis of cancer cells and hence animals maintain good health throughout the experimental period. This model closely mimics the human pathophysiology of breast cancer induced bone pain and has great potential to aid in the process of drug discovery for treating this intractable pain condition.
Highlights
The most common cause of pain in cancer arises from bone metastasis, and around 73% of patients with terminal breast cancer exhibit indications of bone metastases (Coleman, 2006; Currie et al, 2013; Bu et al, 2014)
Nonsteroidal anti-inflammatory drugs are the mainstay of treatment, often in combination with strong opioid analgesics, radiotherapy in the initial stages of metastasis, and adjuvant agents that inhibit osteoclast activity such as bisphosphonates and denosumab (Mantyh et al, 2002; Colvin and Fallon, 2008; Fallon et al, 2016; Fernandes et al, 2016)
Another advantage is that after unilateral intra-tibial injection (ITI), tumor cells do not metastasize to the contralateral tibia during the experimental period and they only cause structural degradation of bones in the ipsilateral limb but not the contralateral limb (Kurth et al, 2001, 2002)
Summary
The most common cause of pain in cancer arises from bone metastasis, and around 73% of patients with terminal breast cancer exhibit indications of bone metastases (Coleman, 2006; Currie et al, 2013; Bu et al, 2014). Growth of Walker 256 cells in the form of tumor is practically independent of the age and weight of the animals at the time of their inoculation (Walpole, 1951) Another advantage is that after unilateral intra-tibial injection (ITI), tumor cells do not metastasize to the contralateral tibia during the experimental period and they only cause structural degradation of bones in the ipsilateral limb but not the contralateral limb (Kurth et al, 2001, 2002). To minimize within- and between- laboratory variability in the use of these cells in vivo, it is important that cultured cells are banked and frozen at early passages, and that culture conditions including growth media, temperature, humidity and exposure to drugs are standardized (Marx, 2014)
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