Colocalization of aromatase in spinal cord astrocytes: Differences in expression and relationship to mechanical and thermal hyperalgesia in murine models of a painful and a non-painful bone tumor

E. E. O'Brien, B. A. Smeester, K. S. Michlitsch, J. H. Lee, A. J. Beitz

Research output: Contribution to journalArticlepeer-review

12 Scopus citations

Abstract

While spinal cord astrocytes play a key role in the generation of cancer pain, there have been no studies that have examined the relationship of tumor-induced astrocyte activation and aromatase expression during the development of cancer pain. Here, we examined tumor-induced mechanical hyperalgesia and cold allodynia, and changes in Glial fibrillary acid protein (GFAP) and aromatase expression in murine models of painful and non-painful bone cancer. We demonstrate that implantation of fibrosarcoma cells, but not melanoma cells, produces robust mechanical hyperalgesia and cold allodynia in tumor-bearing mice compared to saline-injected controls. Secondly, this increase in mechanical hyperalgesia and cold allodynia is mirrored by significant increases in both spinal astrocyte activity and aromatase expression in the dorsal horn of fibrosarcoma-bearing mice. Importantly, we show that aromatase is only found within a subset of astrocytes and not in neurons in the lumbar spinal cord. Finally, administration of an aromatase inhibitor reduced tumor-induced hyperalgesia in fibrosarcoma-bearing animals. We conclude that a painful fibrosarcoma tumor induces a significant increase in spinal astrocyte activation and aromatase expression and that the up-regulation of aromatase plays a role in the development of bone tumor-induced hyperalgesia. Since spinal aromatase is also upregulated, but to a lesser extent, in non-painful melanoma bone tumors, it may also be neuroprotective and responsive to the changing tumor environment.

Original languageEnglish (US)
Pages (from-to)235-245
Number of pages11
JournalNeuroscience
Volume301
DOIs
StatePublished - Aug 1 2015

Bibliographical note

Funding Information:
This work was supported by NIH grant CA084233 and Minnesota AES grant MIN-63-071 .

Publisher Copyright:
© 2015 IBRO.

Copyright:
Copyright 2017 Elsevier B.V., All rights reserved.

Keywords

  • Aromatase
  • Astrocytes
  • Cancer pain
  • Letrozole
  • Mechanical hyperalgesia
  • Spinal cord

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