[Overexpression of heme oxygenase 1 in spinal cord alleviates bone cancer pain in mice].
摘要
OBJECTIVE: To explore the anti-nociceptive effects of heme oxygenase 1 (HO-1) on bone cancer pain in mice. METHODS: The model of bone cancer pain was established by an inoculation of prostate tumor cell line RM-1 cells into intramedullary space of murine femur. Bone destruction and tumor formation in femur were checked by hematoxylin and eosin staining. The mechanical allodynia and heat hyperalgesia were examined by behavioral testing. After intraperitoneal injections of HO-1 inducer (CoPP) and HO-1 inhibitor (SnPP), the protein content of HO-1 in spinal cord was examined by Western blot. RESULTS: The invasion of tumor cells into bone and bone destruction were induced by an injection of RM-1 into right femur. The paw withdrawal threshold (PWL) and paw withdrawal latency (PWL) decreased significantly at 7 days after inoculation and maintained for over 21 days. HO-1 inducer CoPP increased PWT and PWL dramatically in mice with bone cancer pain after consecutive intraperitoneal dosing of CoPP for 5 days. However, SnPP unaltered pain behaviors. Western blot showed the expression of HO-1 in spinal cord was up-regulated after an intraperitoneal injection of CoPP and unchanged after an intraperitoneal injection of SnPP. CONCLUSION: Intramedullary inoculation of prostate tumor cell line RM-1 cells produces bone cancer and induces bone cancer pain. An up-regulation of HO-1 in spinal cord may alleviate bone cancer pain.