To explore the role of PKCγ subunits of rostral anterior cingulate cortex (rACC) neurons in the development of bone cancer pain in rats. Healthy female Sprague-Dawley rats were randomly divided into five groups: blank control group (naive group), sham operation group (sham group), bone cancer pain group (BCP group), BCP plus empty lentiviral vector group (vehicle group) and BCP plus PKCγ/shRNA recombinant lentiviral vector group (PKCγ group). The BCP group, vehicle group and PKCγ group received a 10 µl intra-tibial injection of MADB-106 rat mammary carcinoma cell suspension (4.6×10 8 cell/ml). In comparison, the sham group received a 10 µl intra-tibial injection of saline. The mechanical withdrawal threshold (MWT) and thermal withdrawal latency (TWL) were assessed on pre-operation day 0 (baseline) and days 3, 7, 14 and 21 after intra-tibial injection, respectively. To downregulate the PKCγ subunits of rACC neurons, the PKCγ group received a 10 µl bilateral rACC injection of shRNA/PKCγ recombinant lentivirus (1.25×10 9 TU/ml) on the day 7 after intra-tibial injection, whereas the vehicle group received an injection of the same dose of empty lentiviral vector. Western blotting, immunohistochemical and immunofluorescence analysis were performed to detect the different expression of PKCγ subunits in rACC neurons among these groups on postoperative days 7 or 21. No significant difference in the baseline of MWT and TWL was found among these five groups ( P > 0.05). However, compared with the naive group and sham group, the rats with bone cancer (BCP group, vehicle group and PKCγ group) demonstrated marked mechanical allodynia and thermal hyperalgesia that was evoked starting on postoperative day 7 following intra-tibial injection of carcinoma cells ( P < 0.05). Meanwhile, the western blotting analysis also confirmed that the expression of PKCγ in rACC neurons was significantly increased in the BCP model groups ( P < 0.05). However, from postoperative days 14-21, the injection of shRNA/PKCγ recombinant lentivirus in the PKCγ group alleviated mechanical allodynia and thermal hyperalgesia ( P < 0.05).The present study indicates that up-regulation of PKCγ subunits of rACC neurons in bone cancer pain rats contributes to the development of bone cancer pain.
Background:To explore the role of PKCγ subunit of rACC neurons in the development of bone cancer pain in rats. Methods:40 adult female SD rats were divided into five groups: blank control group (Naive group), sham operation group (Sham group), bone cancer pain group (BCP group),empty lentiviral vector group(Vehicle group) and PKCγ/shRNA recombinant lentiviral vector group (PKCγ group). 10μl MADB-106 rat mammary cancer cells suspension was inoculated into the tibia bone marrow cavity of rats in BCP group and Vehicle group similarly. 10μl saline was inoculated into the proximal tibia bone marrow cavity of rats in Sham group. In the PKCγ group, the rats were taken the same treatment as the BCP group, and then 10μl shRNA/PKCγ recombinant lentivirus was injected into the bilateral rACC on the 7th day. The mechanical withdrawal threshold and thermal withdrawal latency were measured every 3 days to assess the rat pain behavior. Immunohistochemistry, Western blotting technology and immunofluorescence were used to detect the expression of PKCγ subunits in rat rACC neurons after operation. Results: From the 3rd day after operation, the mechanical withdrawal thresholds in BCP group, Vehicle group and PKCγ group were significantly decreased than those in Naive group and Sham group (P<0.05). Compared with the BCP group and Vehicle group the mechanical withdrawal threshold in the PKCγ group increased significantly (P<0.05). On the 3rd postoperative day, the thermal withdrawal latency in BCP, Vehicle and PKCγ groups was significantly longer than those in Naive and Sham groups(P<0.05). From the 14th postoperative day, the TWL in PKCγ group was shorter than that in BCP and Vehicle groups (P<0.05). Western blot analysis showed that the expression of PKCγ in rACC neurons on the 14th day after operation in rats of BCP and Vehicle groups were significantly higher than that in Naive group and Sham group. (P<0.05) However, in the PKCγ group, the expression of PKCγ in rACC neurons was significantly lower than that in BCP group (P<0.05). Conclusion: Up-regulation of PKC subunit of rACC neurons in bone cancer pain rats contributes to the development of pain sensitivity in bone cancer.
To explore the role of PKCγ subunits of rostral anterior cingulate cortex (rACC) neurons in the development of bone cancer pain in rats. Healthy female Sprague-Dawley rats were randomly divided into five groups: blank control group (naive group), sham operation group (sham group), bone cancer pain group (BCP group), BCP plus empty lentiviral vector group (vehicle group) and BCP plus PKCγ/shRNA recombinant lentiviral vector group (PKCγ group). The BCP group, vehicle group and PKCγ group received a 10 µl intra-tibial injection of MADB-106 rat mammary carcinoma cell suspension (4.6×10 8 cell/ml). In comparison, the sham group received a 10 µl intra-tibial injection of saline. The mechanical withdrawal threshold (MWT) and thermal withdrawal latency (TWL) were assessed on pre-operation day 0 (baseline) and days 3, 7, 14 and 21 after intra-tibial injection, respectively. To downregulate the PKCγ subunits of rACC neurons, the PKCγ group received a 10 µl bilateral rACC injection of shRNA/PKCγ recombinant lentivirus (1.25×10 9 TU/ml) on the day 7 after intra-tibial injection, whereas the vehicle group received an injection of the same dose of empty lentiviral vector. Western blotting, immunohistochemical and immunofluorescence analysis were performed to detect the different expression of PKCγ subunits in rACC neurons among these groups on postoperative days 7 or 21. No significant difference in the baseline of MWT and TWL was found among these five groups ( P > 0.05). However, compared with the naive group and sham group, the rats with bone cancer (BCP group, vehicle group and PKCγ group) demonstrated marked mechanical allodynia and thermal hyperalgesia that was evoked starting on postoperative day 7 following intra-tibial injection of carcinoma cells ( P < 0.05). Meanwhile, the western blotting analysis also confirmed that the expression of PKCγ in rACC neurons was significantly increased in the BCP model groups ( P < 0.05). However, from postoperative days 14-21, the injection of shRNA/PKCγ recombinant lentivirus in the PKCγ group alleviated mechanical allodynia and thermal hyperalgesia ( P < 0.05).The present study indicates that up-regulation of PKCγ subunits of rACC neurons in bone cancer pain rats contributes to the development of bone cancer pain.
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