Selective blockade of the capsaicin receptor TRPV1 attenuates bone cancer pain

Joseph R. Ghilardi, Heidi Röhrich, Theodore H. Lindsay, Molly A. Sevcik, Matthew J. Schwei, Kazufumi Kubota, Kyle G. Halvorson, Jeannie Poblete, Sandra R. Chaplan, Adrienne E. Dubin, Nicholas I. Carruthers, Devin Swanson, Michael Kuskowski, Christopher M. Flores, David Julius, Patrick W. Mantyh

Research output: Contribution to journalArticle

294 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)3126-3131
Number of pages6
JournalJournal of Neuroscience
Volume25
Issue number12
DOIs
StatePublished - Mar 23 2005
Externally publishedYes

Keywords

  • Metastasis
  • Nociception
  • Skeletal malignancies
  • Therapy
  • Tumor
  • Vanilloid receptor

ASJC Scopus subject areas

  • Neuroscience(all)

Fingerprint Dive into the research topics of 'Selective blockade of the capsaicin receptor TRPV1 attenuates bone cancer pain'. Together they form a unique fingerprint.

  • Cite this

    Ghilardi, J. R., Röhrich, H., Lindsay, T. H., Sevcik, M. A., Schwei, M. J., Kubota, K., Halvorson, K. G., Poblete, J., Chaplan, S. R., Dubin, A. E., Carruthers, N. I., Swanson, D., Kuskowski, M., Flores, C. M., Julius, D., & Mantyh, P. W. (2005). Selective blockade of the capsaicin receptor TRPV1 attenuates bone cancer pain. Journal of Neuroscience, 25(12), 3126-3131. https://doi.org/10.1523/JNEUROSCI.3815-04.2005