Anti-NGF therapy profoundly reduces bone cancer pain and the accompanying increase in markers of peripheral and central sensitization

Molly A. Sevcik, Joseph R. Ghilardi, Christopher M. Peters, Theodore H. Lindsay, Kyle G. Halvorson, Beth M. Jonas, Kazufumi Kubota, Michael A Kuskowski, Leila Boustany, David L. Shelton, Patrick W. Mantyh

Research output: Contribution to journalArticle

232 Citations (Scopus)

Abstract

Bone cancer pain can be difficult to control, as it appears to be driven simultaneously by inflammatory, neuropathic and tumorigenic mechanisms. As nerve growth factor (NGF) has been shown to modulate inflammatory and neuropathic pain states, we focused on a novel NGF sequestering antibody and demonstrated that two administrations of this therapy in a mouse model of bone cancer pain produces a profound reduction in both ongoing and movement-evoked bone cancer pain-related behaviors that was greater than that achieved with acute administration of 10 or 30 mg/kg of morphine. This therapy also reduced several neurochemical changes associated with peripheral and central sensitization in the dorsal root ganglion and spinal cord, whereas the therapy did not influence disease progression or markers of sensory or sympathetic innervation in the skin or bone. Mechanistically, the great majority of sensory fibers that innervate the bone are CGRP/TrkA expressing fibers, and if the sensitization and activation of these fibers is blocked by anti-NGF therapy there would not be another population of nociceptors, such as the non-peptidergic IB4/RET-IR nerve fibers, to take their place in signaling nociceptive events.

Original languageEnglish (US)
Pages (from-to)128-141
Number of pages14
JournalPain
Volume115
Issue number1-2
DOIs
StatePublished - Jan 1 2005
Externally publishedYes

Fingerprint

Central Nervous System Sensitization
Bone Neoplasms
Nerve Growth Factor
Bone and Bones
Nociceptors
Spinal Ganglia
Neuralgia
Therapeutics
Nerve Fibers
Morphine
Disease Progression
Spinal Cord
Skin
Cancer Pain
Antibodies
Population

Keywords

  • Metastasis
  • NGF
  • Nociception
  • Skeletal malignancies
  • Tumor

Cite this

Sevcik, M. A., Ghilardi, J. R., Peters, C. M., Lindsay, T. H., Halvorson, K. G., Jonas, B. M., ... Mantyh, P. W. (2005). Anti-NGF therapy profoundly reduces bone cancer pain and the accompanying increase in markers of peripheral and central sensitization. Pain, 115(1-2), 128-141. https://doi.org/10.1016/j.pain.2005.02.022

Anti-NGF therapy profoundly reduces bone cancer pain and the accompanying increase in markers of peripheral and central sensitization. / Sevcik, Molly A.; Ghilardi, Joseph R.; Peters, Christopher M.; Lindsay, Theodore H.; Halvorson, Kyle G.; Jonas, Beth M.; Kubota, Kazufumi; Kuskowski, Michael A; Boustany, Leila; Shelton, David L.; Mantyh, Patrick W.

In: Pain, Vol. 115, No. 1-2, 01.01.2005, p. 128-141.

Research output: Contribution to journalArticle

Sevcik, MA, Ghilardi, JR, Peters, CM, Lindsay, TH, Halvorson, KG, Jonas, BM, Kubota, K, Kuskowski, MA, Boustany, L, Shelton, DL & Mantyh, PW 2005, 'Anti-NGF therapy profoundly reduces bone cancer pain and the accompanying increase in markers of peripheral and central sensitization', Pain, vol. 115, no. 1-2, pp. 128-141. https://doi.org/10.1016/j.pain.2005.02.022
Sevcik, Molly A. ; Ghilardi, Joseph R. ; Peters, Christopher M. ; Lindsay, Theodore H. ; Halvorson, Kyle G. ; Jonas, Beth M. ; Kubota, Kazufumi ; Kuskowski, Michael A ; Boustany, Leila ; Shelton, David L. ; Mantyh, Patrick W. / Anti-NGF therapy profoundly reduces bone cancer pain and the accompanying increase in markers of peripheral and central sensitization. In: Pain. 2005 ; Vol. 115, No. 1-2. pp. 128-141.
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