Abstract
Peripheral nerve invasion can occur during cancer progress, which seriously affects the patient's quality of life and brings pain. There is currently no effective treatment method. Therefore, in this study, we established a model of breast cancer bone metastasis and transplanted olfactory sheath cells (OECs) into rats to explore a new cell therapy strategy for treating cancer pain. The results showed that compared with the cancer pain group and the vehicle group (DMEM/F12 medium solution), OEC transplantation improved tibial bone destruction and osteolytic lesions, increased the mechanical withdrawal threshold and thermal withdrawal latency, and alleviated cancer pain behavior in rats. In vitro experiments found that OECs inhibited microglia activation induced by P2X7 receptor (P2X7R) activator BzATP, reduced the expression of IL-1β and IL-18, and protected neuron survival. Further in vivo experiments showed that transplantation of OECs reduced the expression levels of P2X7R, NLRP3, apoptosis-associated spotted protein (ASC), and Caspase-1 in spinal cord tissue, reduced the concentration levels of IL-1β and IL-18 in rat serum, and promoted the growth of peripheral axons. Our conclusions suggest that OEC transplantation may alleviate cancer pain by downregulating P2X7R expression, inhibiting NLRP3/ASC/Caspase-1 signaling, improving neuroinflammatory responses, and thus alleviating cancer pain. These data indicate that OECs may become promising targets for treating cancer pain.