title: 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.
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.
authors.affiliation: Department of Veterinary and Biomedical Sciences, College of Veterinary Medicine, University of Minnesota, St. Paul, MN, USA.
authors.forename: E E
authors.initials: EE
authors.lastname: O'Brien
authors.affiliation: Department of Veterinary and Biomedical Sciences, College of Veterinary Medicine, University of Minnesota, St. Paul, MN, USA.
authors.forename: B A
authors.initials: BA
authors.lastname: Smeester
authors.affiliation: Department of Veterinary and Biomedical Sciences, College of Veterinary Medicine, University of Minnesota, St. Paul, MN, USA.
authors.forename: K S
authors.initials: KS
authors.lastname: Michlitsch
authors.affiliation: Department of Veterinary Physiology, College of Veterinary Medicine and Research Institute for Veterinary Science, Seoul National University, Seoul 151-742, Republic of Korea.
authors.forename: J-H
authors.initials: JH
authors.lastname: Lee
authors.affiliation: Department of Veterinary and Biomedical Sciences, College of Veterinary Medicine, University of Minnesota, 1971 Commonwealth Avenue, St. Paul, MN 55108, USA. Electronic address: beitz001@umn.edu.
authors.forename: A J
authors.initials: AJ
authors.lastname: Beitz
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use; D001141:Aromatase / Q000378:metabolism*; D001859:Bone Neoplasms / Q000150:complications* / Q000188:drug therapy / Q000473:pathology; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D005354:Fibrosarcoma / Q000150:complications / Q000188:drug therapy / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D005904:Glial Fibrillary Acidic Protein; D006930:Hyperalgesia / Q000209:etiology* / Q000473:pathology*; D000077289:Letrozole; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D017628:Microglia / Q000201:enzymology*; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009570:Nitriles / Q000627:therapeutic use; D010146:Pain / Q000150:complications* / Q000209:etiology; D017288:Pain Threshold; D013116:Spinal Cord / Q000473:pathology*; D014230:Triazoles / Q000627:therapeutic use
chemical_list: D000970:Antineoplastic Agents; D005904:Glial Fibrillary Acidic Protein; D009419:Nerve Tissue Proteins; D009570:Nitriles; D014230:Triazoles; C528900:glial fibrillary astrocytic protein, mouse; D000077289:Letrozole; D001141:Aromatase
keywords: aromatase; astrocytes; cancer pain; letrozole; mechanical hyperalgesia; spinal cord