Neural plasticity in pancreatitis and pancreatic cancer

被引:187
作者
Demir, Ihsan Ekin [1 ]
Friess, Helmut [1 ]
Ceyhan, Gueralp O. [1 ]
机构
[1] Tech Univ Munich, Dept Surg, Klinikum Rechts Isar, D-81675 Munich, Germany
关键词
NERVE GROWTH-FACTOR; NITRO-N-NITROSOGUANIDINE; PERINEURAL INVASION; NEUROPATHIC PAIN; MAST-CELLS; RAT MODEL; EXPERIMENTAL CARCINOGENESIS; GASTRIC CARCINOGENESIS; STEM-CELLS; EXPRESSION;
D O I
10.1038/nrgastro.2015.166
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
Pancreatic nerves undergo prominent alterations during the evolution and progression of human chronic pancreatitis and pancreatic cancer. Intrapancreatic nerves increase in size (neural hypertrophy) and number (increased neural density). The proportion of autonomic and sensory fibres (neural remodelling) is switched, and are infiltrated by perineural inflammatory cells (pancreatic neuritis) or invaded by pancreatic cancer cells (neural invasion). These neuropathic alterations also correlate with neuropathic pain. Instead of being mere histopathological manifestations of disease progression, pancreatic neural plasticity synergizes with the enhanced excitability of sensory neurons, with Schwann cell recruitment toward cancer and with central nervous system alterations. These alterations maintain a bidirectional interaction between nerves and non-neural pancreatic cells, as demonstrated by tissue and neural damage inducing neuropathic pain, and activated neurons releasing mediators that modulate inflammation and cancer growth. Owing to the prognostic effects of pain and neural invasion in pancreatic cancer, dissecting the mechanism of pancreatic neuroplasticity holds major translational relevance. However, current in vivo models of pancreatic cancer and chronic pancreatitis contain many discrepancies from human disease that overshadow their translational value. The present Review discusses novel possibilities for mechanistically uncovering the role of the nervous system in pancreatic disease progression.
引用
收藏
页码:649 / 659
页数:11
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