Simple Summary

Cancer-induced bone pain is one of the most debilitating and feared symptoms of cancer patients. Many patients have inadequate pain relief with the current treatment options, and there is a need for new pain medication targeting the mechanisms of cancer-induced bone pain. It has been hypothesized that microglia (cells involved in central nervous system homeostasis) are involved in the signalling of cancer-induced bone pain; however, data from animal models are inconsistent. Here, we apply immunohistochemical staining of the microglial markers ionizing calcium-binding adaptor molecule 1 (Iba-1) and phosphorylated p38-mitogen-activated protein kinase (P-p38 MAPK) to show that microglial reaction is not a feature of cancer-induced bone pain; this independently of disease stage, animal sex or cancer cell-line. Furthermore, pharmacological inhibition of microglia did not affect pain-related behaviours in cancer-bearing rats. Overall, our data support that microglial reaction is not a main player in cancer-induced bone pain.

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.