Major Histocompatibility Complex Class I in Hippocampus Promotes the Comorbid Depressive Symptoms in Cancer Induced Bone Pain via Regulating the Microglial TREM2/DAP12 Signaling

Abstract Pain and depression comorbidity affect the patients’ both physical and mental health and quality of life seriously. The comorbid depressive symptoms in cancer pain severely affect the recognition and treatment of pain. Similarly, cancer pain patients with depression are inclined toward more despair and greater impairment. The mechanisms responsible for the comorbid depressive symptoms in cancer induced bone pain have not been fully delineated and the currently available therapeutics for this pathological pain is relatively limited. In the present study, we observed that carcinoma cells implantation induced pain and depression comorbidity resulted in the upregulation of major histocompatibility complex class I (MHC-I) in hippocampus associated with the activation of TREM2/DAP12-mediated microglial signaling pathways. These observations were reversed by a lentiviral vector harboring RNA interference sequence targeting MHC-I injected into the hippocampus of tumor bearing mice. Together, these results suggest that MHC-I involves in the cancer induced bone pain and depression comorbidity through regulating the TREM2/DAP12-mediated signals in microglia of hippocampus. Suppression of MHC-I could be a therapeutic target for cancer induced bone pain.