Chronic Morphine Administration Causes Increased Bone Loss And Prolonged Neuropathic Pain In A Murine Breast Cancer Model
AuthorCiccone, Haley Anne
AdvisorVanderah, Todd W.
MetadataShow full item record
PublisherThe University of Arizona.
AbstractBreast cancer preferentially metastasizes to bone, stimulating afferent nerve fibers and causing severe, prolonged bone pain. One of the most common therapies to combat cancerinduced bone pain (CIBP) involves the use of opioids, such as morphine, that acts at the Mu opioid receptor (MOR) to alleviate pain. However, recent studies have shown that morphine may exacerbate immune responses by acting through the Toll-like receptor 4 (TLR4) to recruit proinflammatory cytokines and chemokines to the site of metastasis. The purpose of this study was to investigate the underlying mechanism of opioid-induced bone loss. This was done by measuring spontaneous pain behavior and quantifying the amount of lesions in the right hind femur of C57Bl/6 mice inoculated with EO771 breast adenocarcinoma cells after chronic administration of morphine or saline delivered through an osmotic minipump implanted subcutaneously. It was concluded that morphine-treated mice with cancer exhibited paradoxical analgesia after chronic use. Additionally, transgenic MOR and TLR4 knockout mice treated with cancer and morphine displayed a nonsignificant change in bone loss compared to knockouts treated only with cancer and saline, indicating that TLR4 may play a vital role in progressive bone lesion formation following chronic morphine use in a murine metastatic breast cancer model.