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      Use of Animal Models in Understanding Cancer-induced Bone Pain

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          Abstract

          Many common cancers have a propensity to metastasize to bone. Although malignancies often go undetected in their native tissues, bone metastases produce excruciating pain that severely compromises patient quality of life. Cancer-induced bone pain (CIBP) is poorly managed with existing medications, and its multifaceted etiology remains to be fully elucidated. Novel analgesic targets arise as more is learned about this complex and distinct pain state. Over the past two decades, multiple animal models have been developed to study CIBP’s unique pathology and identify therapeutic targets. Here, we review animal models of CIBP and the mechanistic insights gained as these models evolve. Findings from immunocompromised and immunocompetent host systems are discussed separately to highlight the effect of model choice on outcome. Gaining an understanding of the unique neuromolecular profile of cancer pain through the use of appropriate animal models will aid in the development of more effective therapeutics for CIBP.

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          Most cited references 189

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          MicroRNAs: target recognition and regulatory functions.

           David Bartel (2009)
          MicroRNAs (miRNAs) are endogenous approximately 23 nt RNAs that play important gene-regulatory roles in animals and plants by pairing to the mRNAs of protein-coding genes to direct their posttranscriptional repression. This review outlines the current understanding of miRNA target recognition in animals and discusses the widespread impact of miRNAs on both the expression and evolution of protein-coding genes.
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            The capsaicin receptor: a heat-activated ion channel in the pain pathway.

            Capsaicin, the main pungent ingredient in 'hot' chilli peppers, elicits a sensation of burning pain by selectively activating sensory neurons that convey information about noxious stimuli to the central nervous system. We have used an expression cloning strategy based on calcium influx to isolate a functional cDNA encoding a capsaicin receptor from sensory neurons. This receptor is a non-selective cation channel that is structurally related to members of the TRP family of ion channels. The cloned capsaicin receptor is also activated by increases in temperature in the noxious range, suggesting that it functions as a transducer of painful thermal stimuli in vivo.
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              Osteoclast differentiation and activation.

              Osteoclasts are specialized cells derived from the monocyte/macrophage haematopoietic lineage that develop and adhere to bone matrix, then secrete acid and lytic enzymes that degrade it in a specialized, extracellular compartment. Discovery of the RANK signalling pathway in the osteoclast has provided insight into the mechanisms of osteoclastogenesis and activation of bone resorption, and how hormonal signals impact bone structure and mass. Further study of this pathway is providing the molecular basis for developing therapeutics to treat osteoporosis and other diseases of bone loss.
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                Author and article information

                Journal
                Cancer Growth Metastasis
                Cancer Growth Metastasis
                Cancer Growth and Metastasis
                Cancer Growth and Metastasis
                Libertas Academica
                1179-0644
                2015
                23 August 2015
                : 8
                : Suppl 1
                : 47-62
                Affiliations
                Department of Medical Pharmacology, University of Arizona College of Medicine, Tucson, AZ, USA.
                Author notes
                Article
                cgm-suppl.1-2015-047
                10.4137/CGM.S21215
                4552039
                © 2015 the author(s), publisher and licensee Libertas Academica Ltd.

                This is an open-access article distributed under the terms of the Creative Commons CC-BY-NC 3.0 License.

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