Abstract
Pain and depression are common complications in patients with advanced cancer, which significantly affects their quality of life and survival. Dysregulation of the JAK/STAT3 pathway in the central nervous system is associated with pain and brain inflammatory disorders, but its role in bone cancer pain (BCP) remains unclear. This study aimed to investigate the specific role of the JAK/STAT3 pathway in the amygdala in BCP. A BCP rat model was established by intratibial injection of MRMT-1 carcinoma cells. Pain behavior was assessed using the mechanical withdrawal threshold, while depression-like behavior was assessed using the sucrose preference and forced swim test. Changes in inflammatory factors and related protein expression levels in the amygdala were detected using western blotting, immunofluorescence, and reverse transcription-quantitative polymerase chain reaction (RT-qPCR). The effects of intra-amygdala injections of a lentivirus targeting retinoic acid-related orphan receptor γt (RORγt) (LV-shRORγt), nifuroxazide (a STAT3 antagonist), and colivelin (a STAT3 agonist) were evaluated. Rats with BCP demonstrated increased microglial activation in the amygdala. Rats experiencing RORγt knockout in the amygdala showed reduced microglial activation levels. Nifuroxazide reduced Th17 cell differentiation, potentially alleviating pain and depression-like behaviors. To further explore the underlying relationship between the JAK/STAT3 pathway and Th17 cells, LV-shRORγt and a STAT3 agonist were co-administered. The inhibitory effect of LV-shRORγt counteracted the STAT3 agonist's active effects. Our study showed that targeting JAK/STAT3 signaling alleviated pain- and depression-like behaviors in rats with BCP by inhibiting Th17 cell differentiation.
Published Version
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call