Abstract
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.
Highlights
The dissemination of cancer to bone can lead to significant pain, with up to 85% of patients experiencing cancer-induced bone pain (CIBP) [1,2,3]
Through immunohistochemical characterization of ionizing calcium-binding adaptor molecule 1 (Iba-1) and phosphorylated p38-mitogen-activated protein kinase (P-p38 MAPK), two markers of microglial reaction [25], and through pharmacological microglial inhibition our findings suggest that microglial reaction is not a main feature of this model of CIBP; this is independently of disease stage, rat sex, and cancer cell line inoculated
No significant difference was found in the number of Walker 256 model of CIBP focus on females [26,30,31,32], we addressed whether microglial reaction present cancer-bearing male rats.ofNo significant difference wasrats found in the number of Iba-1 cells was between theinipsilateral dorsal horn cancer-bearing and sham
Summary
The dissemination of cancer to bone can lead to significant pain, with up to 85% of patients experiencing cancer-induced bone pain (CIBP) [1,2,3]. The most commonly used involve the inoculation of syngeneic carcinoma cell lines in the intramedullary cavity of a long bone (e.g., tibia or femur), leading to the localized development of osteolytic bone lesions and pain-like behaviors [15,16,17]. These models have been useful to advance our knowledge of CIBP, demonstrating that this pain type shares nociceptive and neuropathic pain components and presents with its own characteristics and neurochemical signature [18,19,20]
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