title: Spinal glial activation in a new rat model of bone cancer pain produced by prostate cancer cell inoculation of the tibia.
abstract: Studies suggest that astrocytes and microglia in the spinal cord are involved in the development of persistent pain induced by tissue inflammation and nerve injury. However, the role of glial cells in bone cancer pain is not well understood. The present study evaluated the spinal glial activation in a novel rat model of bone cancer pain produced by injecting AT-3.1 prostate cancer cells into the unilateral tibia of male Copenhagen rats. The structural damage to the tibia was monitored by radiological analysis. The thermal hyperalgesia, mechanical hyperalgesia and allodynia, and spontaneous flinch were measured. The results showed that: (1) inoculation of prostate cancer cells, but not the vehicle Hank's solution, induced progressive bone destruction at the proximal epiphysis of the tibia from day 7-20 post inoculation; (2) the inoculation also induced progressive thermal hyperalgesia, mechanical hyperalgesia, mechanical allodynia, and spontaneous flinches; (3) astrocytes and microglia were significantly activated in the spinal cord ipsilateral to the cancer leg, characterized by enhanced immunostaining of both glial fibrillary acidic protein (GFAP, astrocyte marker) and OX-42 (microglial marker); (4) IL-1beta was up-regulated in the ipsilateral spinal cord, evidenced by an increase of IL-1beta immunostained astrocytes. These results demonstrate that injection of AT-3.1 prostate cancer cells into the tibia produces progressive hyperalgesia and allodynia associated with the progression of tibia destruction, indicating the successful establishment of a novel male rat model of bone cancer pain. Further, bone cancer activates spinal glial cells, which may release IL-1beta and other cytokines and contribute to hyperalgesia.
authors.affiliation: Center For Integrative Medicine, School of Medicine, University of Maryland, 3rd Floor, James Kernan Hospital Mansion, 2200 Kernan Drive, Baltimore, MD 21207, USA. rzhan001@umaryland.edu
authors.forename: Rui-Xin
authors.initials: RX
authors.lastname: Zhang
authors.forename: Bing
authors.initials: B
authors.lastname: Liu
authors.forename: Linbo
authors.initials: L
authors.lastname: Wang
authors.forename: Ke
authors.initials: K
authors.lastname: Ren
authors.forename: Jian-Tian
authors.initials: JT
authors.lastname: Qiao
authors.forename: Brian M
authors.initials: BM
authors.lastname: Berman
authors.forename: Lixing
authors.initials: L
authors.lastname: Lao
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000378:metabolism; D001859:Bone Neoplasms / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology*; D017690:Cell Transplantation / Q000473:pathology; D004195:Disease Models, Animal; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006614:Hindlimb / Q000473:pathology / Q000503:physiopathology*; D006930:Hyperalgesia / Q000378:metabolism / Q000503:physiopathology; D007375:Interleukin-1 / Q000378:metabolism; D008297:Male; D009368:Neoplasm Transplantation / Q000473:pathology*; D009457:Neuroglia / Q000166:cytology / Q000378:metabolism*; D010146:Pain / Q000378:metabolism / Q000503:physiopathology*; D011467:Prostate / Q000473:pathology*; D011471:Prostatic Neoplasms / Q000473:pathology* / Q000556:secondary*; D051381:Rats; D013116:Spinal Cord / Q000166:cytology* / Q000378:metabolism*
chemical_list: D005904:Glial Fibrillary Acidic Protein; D007375:Interleukin-1