Targeting PI3K-mTOR signaling in the anterior cingulate cortex improves emotional behavior, and locomotor activity in rats with bone cancer pain.

OBJECTIVE: To investigate the effects of targeting the PI3K-mTOR signaling pathway in the anterior cingulate cortex (ACC) on pain responses, locomotor activity, and emotional behavior in rats with bone cancer pain. METHODS: Bone cancer pain was induced by implanting Walker 256 cells into the rat. Pain responses were assessed using paw withdrawal threshold and latency measurements, while locomotor activity and negative mood were evaluated through open field and conditioned place aversion tests, respectively. RESULTS: The results showed that the bone cancer pain model led to allodynia, hyperalgesia, decreased ambulation, and ACC microglial activation. Morphine treatment improved pain responses but did not affect locomotor activity or mTOR protein expression. In contrast, rapamycin treatment reduced pain, improved locomotor activity, and decreased negative mood. It also downregulated PI3K-mTOR protein expression. Furthermore, inhibiting the PI3K-mTOR pathway with a PI3K inhibitor or rapamycin not only improved pain responses and locomotor activity but also reduced depression and anxiety-like behaviors. These effects were accompanied by changes in paw withdrawal threshold, latency, static time, and PI3K-mTOR protein expression. CONCLUSIONS: Targeting the PI3K-mTOR signaling pathway in the ACC effectively alleviates pain-related symptoms and emotional disturbances in rats with bone cancer pain. This approach holds promise for alleviating pain and allaying negative emotion after further study.