RT Journal Article SR Electronic T1 Selective Blockade of the Capsaicin Receptor TRPV1 Attenuates Bone Cancer Pain JF The Journal of Neuroscience JO J. Neurosci. FD Society for Neuroscience SP 3126 OP 3131 DO 10.1523/JNEUROSCI.3815-04.2005 VO 25 IS 12 A1 Joseph R. Ghilardi A1 Heidi Röhrich A1 Theodore H. Lindsay A1 Molly A. Sevcik A1 Matthew J. Schwei A1 Kazufumi Kubota A1 Kyle G. Halvorson A1 Jeannie Poblete A1 Sandra R. Chaplan A1 Adrienne E. Dubin A1 Nicholas I. Carruthers A1 Devin Swanson A1 Michael Kuskowski A1 Christopher M. Flores A1 David Julius A1 Patrick W. Mantyh YR 2005 UL http://www.jneurosci.org/content/25/12/3126.abstract AB Cancer colonization of bone leads to the activation of osteoclasts, thereby producing local tissue acidosis and bone resorption. This process may contribute to the generation of both ongoing and movement-evoked pain, resulting from the activation of sensory neurons that detect noxious stimuli (nociceptors). The capsaicin receptor TRPV1 (transient receptor potential vanilloid subtype 1) is a cation channel expressed by nociceptors that detects multiple pain-producing stimuli, including noxious heat and extracellular protons, raising the possibility that it is an important mediator of bone cancer pain via its capacity to detect osteoclast- and tumor-mediated tissue acidosis. Here, we show that TRPV1 is present on sensory neuron fibers that innervate the mouse femur and that, in an in vivo model of bone cancer pain, acute or chronic administration of a TRPV1 antagonist or disruption of the TRPV1 gene results in a significant attenuation of both ongoing and movement-evoked nocifensive behaviors. Administration of the antagonist had similar efficacy in reducing early, moderate, and severe pain-related responses, suggesting that TRPV1 may be a novel target for pharmacological treatment of chronic pain states associated with bone cancer metastasis.