PT  - JOURNAL ARTICLE
AU  - Liang Han
AU  - Jie Jiang
AU  - Mengwen Xue
AU  - Tao Qin
AU  - Ying Xiao
AU  - Erxi Wu
AU  - Xin Shen
AU  - Qingyong Ma
AU  - Jiguang Ma
TI  - Sonic hedgehog signaling pathway promotes pancreatic cancer pain via nerve growth factor
AID  - 10.1136/rapm-2019-100991
DP  - 2019 Nov 29
TA  - Regional Anesthesia & Pain Medicine
PG  - rapm-2019-100991
4099  - http://rapm.bmj.com/content/early/2019/11/29/rapm-2019-100991.short
4100  - http://rapm.bmj.com/content/early/2019/11/29/rapm-2019-100991.full
AB  - Background Many patients with pancreatic cancer (PC) suffer from abdominal pain and back pain. However, the cause of pain associated with PC is largely unclear. In this study, we tested the potential influence of the sonic hedgehog (sHH) signaling pathway on PC pain.Methods Substance P (SP) and calcitonin gene-related peptide (CGRP) expression was measured in cultured PC cells and dorsal root ganglions (DRG) by real-time PCR, western blotting analysis and ELISA. Small interfering RNA transfection and plasmid constructs were used to regulate the expression of sHH in the AsPc-1 and Panc-1 cell lines. Pain-related behavior was observed in an orthotopic tumor model in nude mice.Results In this study, the results show that sHH increased the expression of SP and CGRP in DRGs in a concentration and time-dependent manner. Additionally, sHH secretion from PC cells could activate the sHH signaling pathway and, in turn, increase the expression of nerve growth factor (NGF), P75, and TrkA in DRGs. Furthermore, the sHH signaling pathway and NGF/NGF receptor contributed to pain sensitivity in a nude mouse model.Conclusion Our results demonstrate that PC pain originates from the sHH signaling pathway, and NGF mediates the pain mechanism via regulating SP and CGRP.