Author:
Han Liang,Jiang Jie,Xue Mengwen,Qin Tao,Xiao Ying,Wu Erxi,Shen Xin,Ma Qingyong,Ma Jiguang
Abstract
BackgroundMany 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.MethodsSubstance 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.ResultsIn 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.ConclusionOur results demonstrate that PC pain originates from the sHH signaling pathway, and NGF mediates the pain mechanism via regulating SP and CGRP.
Funder
National Natural Science Foundation of China
Subject
Anesthesiology and Pain Medicine,General Medicine
Reference31 articles.
1. Cancer statistics, 2019;Siegel;CA Cancer J Clin,2019
2. Cancer statistics in China, 2015;Chen;CA Cancer J Clin,2016
3. Road map for pain management in pancreatic cancer: a review;Lahoud;World J Gastrointest Oncol,2016
4. Perineural invasion and associated pain in pancreatic cancer;Bapat;Nat Rev Cancer,2011
5. New insights into perineural invasion of pancreatic cancer: more than pain;Liang;Biochim Biophys Acta,2016
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