Modulation of Rat Cancer-Induced Bone Pain is Independent of Spinal Microglia Activity

The dissemination of cancer to bone can cause significant cancer-induced bone pain (CIBP), severely impairing the patient’s quality of life. Several rodent models have been developed to explore the nociceptive mechanisms of CIBP, including intratibial inoculation of breast carcinoma cells in syngene...

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Bibliographic Details
Published in:Cancers 2020-10, Vol.12 (10), p.2740
Main Authors: Diaz-delCastillo, Marta, Hansen, Rie Bager, Appel, Camilla Kristine, Nielsen, Lykke, Nielsen, Sascha Nolsøe, Karyniotakis, Konstantinos, Dahl, Louise M., Andreasen, Rikke B., Heegaard, Anne-Marie
Format: Article
Language:English
Subjects:
Analgesics
Animal models
Bone cancer
Bone density
Breast cancer
Breast carcinoma
Calcium
Central nervous system
Females
Homeostasis
Inoculation
Kinases
MAP kinase
Microglia
Microglial cells
Minocycline
Morphine
Neuralgia
Pain
Pain perception
Patients
Physiological aspects
Protein kinase
Quality of life
Rodents
Spinal cord
Therapeutic targets
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Summary:The dissemination of cancer to bone can cause significant cancer-induced bone pain (CIBP), severely impairing the patient’s quality of life. Several rodent models have been developed to explore the nociceptive mechanisms of CIBP, including intratibial inoculation of breast carcinoma cells in syngeneic Sprague Dawley rats. Using this model, we investigated whether resident spinal microglial cells are involved in the transmission and modulation of CIBP, a long-debated disease feature. Immunohistochemical staining of ionizing calcium-binding adaptor molecule 1 (Iba-1) and phosphorylated p38-mitogen-activated protein kinase (P-p38 MAPK) showed no spinal microglial reaction in cancer-bearing rats, independently of disease stage, sex, or carcinoma cell line. As a positive control, significant upregulation of both Iba-1 and P-p38 was observed in a rat model of neuropathic pain. Additionally, intrathecal administration of the microglial inhibitor minocycline did not ameliorate pain-like behaviors in cancer-bearing rats, in contrast to spinal morphine administration. Our results indicate that microglial reaction is not a main player in CIBP, adding to the debate that even within the same models of CIBP, significant variations are seen in disease features considered potential drug targets. We suggest that this heterogeneity may reflect the clinical landscape, underscoring the need for understanding the translational value of CIBP models.
ISSN:2072-6694
2072-6694
DOI:10.3390/cancers12102740