Neurochemical and cellular reorganization of the spinal cord in a murine model of bone cancer pain

Matthew J. Schwei, Prisca Honore, Scott D. Rogers, Janeen L. Salak-Johnson, Matthew P. Finke, Margaret L. Ramnaraine, Denis R. Clohisy, Patrick W Mantyh

Research output: Contribution to journalArticle

439 Citations (Scopus)

Abstract

The cancer-related event that is most disruptive to the cancer patient's quality of life is pain. To begin to define the mechanisms that give rise to cancer pain, we examined the neurochemical changes that occur in the spinal cord and associated dorsal root ganglia in a murine model of bone cancer. Twenty-one days after intramedullary injection of osteolytic sarcoma cells into the femur, there was extensive bone destruction and invasion of the tumor into the periosteum, similar to that found in patients with osteolytic bone cancer. In the spinal cord, ipsilateral to the cancerous bone, there was a massive astrocyte hypertrophy without neuronal loss, an expression of dynorphin and c-Fos protein in neurons in the deep laminae of the dorsal horn. Additionally, normally non-noxious palpation of the bone with cancer induced behaviors indicative of pain, the internalization of the substance P receptor, and c-Fos expression in lamina I neurons, The alterations in the neurochemistry of the spinal cord and the sensitization of primary afferents were positively correlated with the extent of bone destruction and the growth of the tumor. This 'neurochemical signature' of bone cancer pain appears unique when compared to changes that occur in persistent inflammatory or neuropathic pain states. Understanding the mechanisms by which the cancer cells induce this neurochemical reorganization may provide insight into peripheral factors that drive spinal cord plasticity and in the development of more effective treatments for cancer pain.

Original languageEnglish (US)
Pages (from-to)10886-10897
Number of pages12
JournalJournal of Neuroscience
Volume19
Issue number24
StatePublished - Dec 15 1999
Externally publishedYes

Fingerprint

Bone Neoplasms
Spinal Cord
Neoplasms
Proto-Oncogene Proteins c-fos
Neurochemistry
Neurokinin-1 Receptors
Neurons
Bone and Bones
Dynorphins
Pain
Periosteum
Palpation
Bone Development
Spinal Ganglia
Neuralgia
Astrocytes
Sarcoma
Femur
Hypertrophy
Quality of Life

Keywords

  • Astrocyte
  • Gliosis
  • Nociception
  • Osteolysis
  • Primary afferents
  • Sensitization

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Schwei, M. J., Honore, P., Rogers, S. D., Salak-Johnson, J. L., Finke, M. P., Ramnaraine, M. L., ... Mantyh, P. W. (1999). Neurochemical and cellular reorganization of the spinal cord in a murine model of bone cancer pain. Journal of Neuroscience, 19(24), 10886-10897.

Neurochemical and cellular reorganization of the spinal cord in a murine model of bone cancer pain. / Schwei, Matthew J.; Honore, Prisca; Rogers, Scott D.; Salak-Johnson, Janeen L.; Finke, Matthew P.; Ramnaraine, Margaret L.; Clohisy, Denis R.; Mantyh, Patrick W.

In: Journal of Neuroscience, Vol. 19, No. 24, 15.12.1999, p. 10886-10897.

Research output: Contribution to journalArticle

Schwei, MJ, Honore, P, Rogers, SD, Salak-Johnson, JL, Finke, MP, Ramnaraine, ML, Clohisy, DR & Mantyh, PW 1999, 'Neurochemical and cellular reorganization of the spinal cord in a murine model of bone cancer pain', Journal of Neuroscience, vol. 19, no. 24, pp. 10886-10897.
Schwei MJ, Honore P, Rogers SD, Salak-Johnson JL, Finke MP, Ramnaraine ML et al. Neurochemical and cellular reorganization of the spinal cord in a murine model of bone cancer pain. Journal of Neuroscience. 1999 Dec 15;19(24):10886-10897.
Schwei, Matthew J. ; Honore, Prisca ; Rogers, Scott D. ; Salak-Johnson, Janeen L. ; Finke, Matthew P. ; Ramnaraine, Margaret L. ; Clohisy, Denis R. ; Mantyh, Patrick W. / Neurochemical and cellular reorganization of the spinal cord in a murine model of bone cancer pain. In: Journal of Neuroscience. 1999 ; Vol. 19, No. 24. pp. 10886-10897.
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