Fig. 6.
Effects of continuous subcutaneous administration of QX-314 on phosphorylated cyclic adenosine monophosphate response element–binding protein (p-CREB) expression in L2 dorsal root ganglion (DRG) neurons of sarcoma-implanted mice. (A) Immunohistochemical staining for transient receptor potential vanilloid subfamily 1 (TRPV1; green) with p-CREB (red) in L2 DRG neurons of sarcoma-implanted mice after continuous subcutaneous administration of a vehicle or QX-314 (5 mg kg−1 h−1) for 48 h. White arrows indicate p-CREB–immunoreactive neurons expressed in TRPV1-immunoreactive neurons. Scale bar = 50 μm. (B) Percentages of p-CREB–positive profiles in TRPV1-positive DRG neurons. n = 3 for naive mice and n = 6 in the other groups. (C) Percentages of p-CREB–positive profiles in TRPV1-negative DRG neurons. n = 3 for naive mice and n = 6 in the other groups. Data for percentages of p-CREB–positive profiles in TRPV1-positive DRG neurons or in TRPV1-negative DRG neurons are presented as means ± SDs. In naive mice, 33.8 ± 2.1% of TRPV1-positive DRG neurons were p-CREB positive (p-CREB–positive count/total TRPV1-positive count = 658/1948), and 31.1 ± 7.5% of TRPV1-negative DRG neurons were p-CREB positive (p-CREB–positive count/total TRPV1-negative count = 867/2787) (B, C). These results represent averaged proportions obtained from 27 DRG sections. Sarcoma implantation, but not sham implantation, significantly increased the expression of p-CREB in TRPV1-positive and TRPV1-negative DRG neurons (B, C). QX-314 reduced p-CREB expression in TRPV1-positive, but not TRPV1-negative, DRG neurons (B, C). In QX-314–treated mice, 32.2 ± 3.0% of TRPV1-positive DRG neurons were p-CREB–positive (p-CREB–positive count/total TRPV1-positive count = 926/2887), and in vehicle-treated mice, 52.6 ± 5.9% of TRPV1-positive DRG neurons were p-CREB positive (p-CREB–positive count/total TRPV1-positive count = 1703/3266). In QX-314–treated mice, 41.7 ± 4.5% of TRPV1-negative DRG neurons were p-CREB positive (p-CREB–positive count/total TRPV1-negative count = 1586/3777), and in vehicle-treated mice, 42.1 ± 4.7% of TRPV1-negative DRG neurons were p-CREB positive (p-CREB–positive count/total TRPV1-negative count = 2146/5107). These results represent averaged proportions obtained from 54 DRG sections in QX-314–treated mice and 49 DRG sections in vehicle-treated mice. *P < 0.05 versus sham. #P < 0.001 versus sham. **P < 0.001 versus vehicle.