胰腺癌性痛发生、发展的神经机制研究进展

邱欣彤; 李仪; 曹鹏; 张明明

doi:10.16098/j.issn.0529-1356.2021.04.026

PDF(875 KB)

解剖学报 ›› 2021, Vol. 52 ›› Issue (4) : 670-674. DOI: 10.16098/j.issn.0529-1356.2021.04.026

综述

胰腺癌性痛发生、发展的神经机制研究进展

邱欣彤^1,2 李仪^1,3曹鹏^1,4张明明^1*

作者信息 +

Research progress on neural mechanism of pancreatic cancer pain

QIU Xin-tong^1,2 LI Yi^1,3 CAO Peng^1,4 ZHANG Ming-ming^1*

Author information +

文章历史 +

摘要

胰腺癌性痛属于癌症引起的内脏痛，患者常常具有左上腹疼痛的特点，且在背部呈带状放射，严重影响患者的预后和生活质量。胰腺属于腹膜后位器官，周围有大量的神经丛包绕，受交感神经和副交感神经的共同支配。胰腺癌性痛机制复杂，如胰腺癌肿瘤细胞对周围神经的侵袭、肥大细胞脱颗粒物使受体激活、新生毛细血管增生、神经胶质细胞参与以及多种分子水平机制等。掌握胰腺的神经解剖学特征，探索胰腺癌性痛的机制对于临床治疗胰腺癌患者疼痛以及提高其预后和生活质量非常必要。我们就胰腺癌的神经病理性痛机制做一综述，以期为临床治疗胰腺癌性痛提供新的靶点和策略。

Abstract

Pancreatic cancer pain is a kind of visceral pain caused by cancer. Patients often have the characteristics of left upper abdominal pain and band radiation on the back, which seriously affects the prognosis and quality of life of the patients. Pancreas is a retroperitoneal organ and distributed with sympathetic nerve and parasympathetic nerve. The mechanism of pancreatic cancer pain is complex, such as the invasion of peripheral nerve by tumor cells, the activation of receptor by mastocyte departiculate action, the proliferation of new capillaries, the involvement of glial cells, and the related molecular mechanisms. It is necessary to understand the neuroanatomical characteristics of pancreas and explore the mechanism of pancreatic cancer pain in order to relieve the pain and improve the prognosis and quality of life of patients with pancreatic cancer. In this paper, the neuropathic pain mechanism of pancreatic cancer is reviewed in order to provide a new target and strategy for clinical treatment.

导出引用

邱欣彤李仪曹鹏张明明. 胰腺癌性痛发生、发展的神经机制研究进展[J]. 解剖学报. 2021, 52(4): 670-674 https://doi.org/10.16098/j.issn.0529-1356.2021.04.026

QIU Xin-tong LI Yi CAO Peng ZHANG Ming-ming. Research progress on neural mechanism of pancreatic cancer pain[J]. Acta Anatomica Sinica. 2021, 52(4): 670-674 https://doi.org/10.16098/j.issn.0529-1356.2021.04.026

中图分类号： Q189

参考文献

［1］ Ilic M, Ilic I. Epidemiology of pancreatic cancer［J］. World J Gastroenterol,2016 22(44):9694-9705.

［2］ Tando Y, Yanagimachi M, Matsuhashi Y, et al. A brief outline of the history of the pancreatic anatomy［J］. Dig Surg, 2010,27(2):84-86.

［3］ So M, Bansal N, Piracha MM. Neuromodulation and pancreatic cancer pain［J］. J Palliat Med,2018,21(8): 1064-1066.

［4］ Leung PS. Overview of the pancreas［J］. Adv Exp Med Biol,2010,690:3-12.

［5］ Skandalakis LJ, Rowe JS Jr, Gray SW, et al. Surgical embryology and anatomy of the pancreas［J］. Surg Clin North Am, 1993,73(4):661-697.

［6］ Hagai H. Configurational anatomy of the pancreas: its surgical relevance from ontogenetic and comparative-anatomical viewpoints［J］. J Hepatobiliary Pancreat Surg, 2003,10(1):48-56.

［7］ Lindsay TH, Halvorson KG, Peters CM, et al. A quantitative analysis of the sensory and sympathetic innervation of the mouse pancreas［J］. Neuroscience, 2006,137(4):1417-1426.

［8］ Nedergaard J, Alexson S, Cannon B. Cold adaptation in the rat: increased brown fat peroxisomal beta-oxidation relative to maximal mitochondrial oxidative capacity［J］. Am J Physiol,1980,239(5):C208-216.

［9］ Rack FJ, Elkins CW. Experiences with vagotomy and sympathectomy in the treatment of chronic recurrent pancreatitis［J］. AMA Arch Surg,1950,61(5):937-943.

［10］ Rodriguez-Diaz R, Abdulreda MH, Formoso AL, et al. Innervation patterns of autonomic axons in the human endocrine pancreas［J］. Cell Metab,2011,14(1):45-54.

［11］ Henry BM, Skinningsrud B, Saganiak K, et al. Development of the human pancreas and its vasculature-An integrated review covering anatomical, embryological, histological, and molecular aspects［J］. Ann Anat,2019,221:115-124.

［12］ Bonica JJ. Autonomic innervation of the viscera in relation to nerve block［J］. Anesthesiology,1968,29(4):793-813.

［13］ Kato K, Ikeura T, Yanagawa M, et al. Morphological and immunohistochemical comparison of intrapancreatic nerves between chronic pancreatitis and type 1 autoimmune pancreatitis［J］. Pancreatology,2017,17(3):403-410.

［14］ Gupta R, Amanam I, Chung V. Current and future therapies for advanced pancreatic cancer［J］. J Surg Oncol,2017,116(1):25-34.

［15］ Bj?rnsson B, Sandstr?m P. Laparoscopic distal pancreatectomy for adenocarcinoma of the pancreas［J］. World J Gastroenterol,2014,20(37):13402-13411.

［16］ Dobosz ? , Kaczor M, Stefaniak TJ. Pain in pancreatic cancer: review of medical and surgical remedies［J］. ANZ J Surg,2016,86(10):756-761.

［17］ J?nig W. Neurobiology of visceral pain［J］. Schmerz,2014,28(3):233-251.

［18］ Wang L, Xu H, Ge Y, et al. Establishment of a murine pancreatic cancer pain model and microarray analysis of painassociated genes in the spinal cord dorsal horn［J］. Mol Med Rep,2017,16(4):4429-4436.

［19］ Gebhart GF, Bielefeldt K. Physiology of visceral pain［J］. Compr Physiol,2016,6(4):1609-1633.

［20］ Carr RA, Roch AM, Zhong X, et al. Prospective evaluation of associations between cancer-related pain and perineural invasion in patients with resectable pancreatic adenocarcinoma［J］. J Gastrointest Surg,2017,21(10):1658-1665.

［21］ Zhang Y. Molecular mechanism of moesin in pancreatic cancer and its correlation with pain［D］. Tianjin: Tianjin Medical University,2009. (in Chinese)

张彧. moesin在胰腺癌嗜神经性中的分子机制及与疼痛的相关性［D］. 天津：天津医科大学,2009.

［22］ Liang L, Dong M, Cong K, et al. Correlations of moesin expression with the pathological stage, nerve infiltration, tumor location and pain severity in patients with pancreatic cancer［J］. J BUON,2019,24(3):1225-1232.

［23］ Abiatari I, Esposito I, Oliveira TD, et al. Moesin-dependent cytoskeleton remodelling is associated with an anaplastic phenotype of pancreatic cancer［J］. J Cell Mol Med,2010,14(5):1166-1179.

［24］ Bapat AA, Munoz RM, Von Hoff DD, et al. Blocking nerve growth factor signaling reduces the neural invasion potential of pancreatic cancer cells［J］. PLoS One,2016,11(10):e0165586.

［25］ Jobling P, Pundavela J, Oliveira SM, et al. Nerve-cancer cell cross-talk: a novel promoter of tumor progression［J］. Cancer Res,2015,75(9):1777-1781.

［26］ Boilly B, Faulkner S, Jobling P, et al. Nerve dependence: from regeneration to cancer［J］. Cancer Cell,2017,31(3):342-354.

［27］ Longo V, Tamma R, Brunetti O, et al. Mast cells and angiogenesis in pancreatic ductal adenocarcinoma［J］. Clin Exp Med,2018,18(3):319-323.

［28］ Yu DW. Study on the role and mechanism of mast cell departiculate matter in pancreatic cancer pain［D］. Shanghai: Second Military Medical University,2013. (in Chinese)

虞大为. 肥大细胞脱颗粒物在胰腺癌疼痛中的作用及其机制研究［D］. 上海：第二军医大学,2013.

［29］ Guo X, Zhai L, Xue R, et al. Mast cell tryptase contributes to pancreatic cancer growth through promoting angiogenesis via activation of angiopoietin-1［J］. Int J Mol Sci,2016,17(6): 834.

［30］ Hung CY, Tan CH. TRP channels in nociception and pathological pain［J］. Adv Exp Med Biol,2018,1099:13-27.

［31］ Zhang MM. Mechanism of central transmission and regulation of pelvic visceral pain information［D］. Xi’an: Fourth Military Medical University,2014. (in Chinese)

张明明. 盆腔内脏痛信息在中枢传递与调控的机制［D］. 西安：第四军医大学,2014.

［32］ Zhu J, Miao XR, Tao KM, et al. Trypsin-protease activated receptor-2 signaling contributes to pancreatic cancer pain［J］. Oncotarget,2017,8(37): 61810-61823.

［33］ Amaya F, Shimosato G, Nagano M, et al. NGF and GDNF differentially regulate TRPV1 expression that contributes to development of inflammatory thermal hyperalgesia［J］. Eur J Neurosc,2004,20(9):2303-2310.

［34］ Witte D, Zeeh F, G?deken T, et al. Proteinase-activated receptor 2 is a novel regulator of TGF-β signaling in pancreatic cancer［J］. J Clin Med,2016,5(12): 111.

［35］ Xie L, Duan Z, Liu C, et al. Protease-activated receptor 2 agonist increases cell proliferation and invasion of human pancreatic cancer cells［J］. Exp Ther Med,2015,9(1):239-244.

［36］ Yu D, Zhu J, Zhu M, et al. Inhibition of mast cell degranulation relieves visceral hypersensitivity induced by pancreatic carcinoma in mice［J］. J Mol Neurosci,2019,69(2):235-245.

［37］ Barreto SG, Saccone GT. Pancreatic nociception-revisiting the physiology and pathophysiology［J］. Pancreatology,2012,12(2):104-112.

［38］ Ceyhan GO, Michalski CW, Demir IE, et al. Pancreatic pain［J］. Best Pract Res Clin Gastroenterol,2008,22(1):31-44.

［39］ Elliott AA, Elliott JR. Characterization of TTX-sensitive and TTX-resistant sodium currents in small cells from adult rat dorsal root ganglia［J］. J Physiol,1993,463:39.

[40] Lastraioli E, Iorio J, Arcangeli A. Ion channel expression as promising cancer biomarker [J]. Biochim Biophys Acta, 2015,1848(10pt B):2685-2702.

［41］ Godazgar M, Zhang Q, Chibalina MV, et al. Biphasic voltage-dependent inactivation of human NaV 1.3, 1.6 and 1.7 Na+ channels expressed in rodent insulinsecreting cells［J］. J Physiol,2018,596(9):1601-1626.

［42］ Berta T, Qadri Y, Tan PH, et al. Targeting dorsal root ganglia and primary sensory neurons for the treatment of chronic pain［J］. Expert Opin Ther Targets,2017,21(7):695-703.

［43］ Tréhoux S, Lahdaoui F, Delpu Y, et al. Micro-RNAs miR-29a and miR-330-5p function as tumor suppressors by targeting the MUC1 mucin in pancreatic cancer cells［J］. Biochim Biophys Acta,2015,1853(10 Pt A):2392-2403.

［44］ Wang LQ. Mechanism of mir-330 inhibiting GABAB receptor function in spinal cord neurons to mediate pancreatic cancer pain［D］. Shanghai: Second Military Medical University,2015. (in Chinese)

［45］ Demir IE, Ceyhan GO, Rauch U, et al. The microenvironment in chronic pancreatitis and pancreatic cancer induces neuronal plasticity［J］. Neurogastroenterol Motil,2010,22(4):480-490.

［46］ Demir IE, Friess H, Ceyhan GO. Neural plasticity in pancreatitis and pancreatic cancer［J］. Nat Rev Gastroenterol Hepatol,2015,12(11):649-659.

［47］ Alrawashdeh W, Jones R, Dumartin L, et al. Perineural invasion in pancreatic cancer: proteomic analysis and in vitro modelling［J］. Mol Oncol,2019,13(5):1075-1091.

［48］ Demir IE, Tieftrunk E, Schorn S, et al. Activated Schwann cells in pancreatic cancer are linked to analgesia via suppression of spinal astroglia and microglia［J］. Gut,2016,65(6):1001-1014.

［49］ Costache MI, Ioana M, Iordache S, et al. VEGF expression in pancreatic cancer and other malignancies: a review of the literature［J］. Rom J Intern Med,2015,53(3):199-208.

［50］ Abiatari I, Midelashvili T, Motsikulashvili M, et al. Overexpressed progenitor gene CSF1R in pancreatic cancer tissues and nerve invasive pancreatic cancer cells［J］. Georgian Med News,2018,(285):96-100.

［51］ Bennett MI. Mechanism-based cancer-pain therapy［J］. Pain,2017,158 (Suppl 1):S74-S78.

［52］ Mercadante S, Tirelli W, David F, et al. Morphine versus oxycodone in pancreatic cancer pain: a randomized controlled study［J］. Clin J Pain,2010,26(9):794-797.

［53］ Rossi ML, Rehman AA, Gondi CS. Therapeutic options for the management of pancreatic cancer［J］. World J Gastroenterol,2014,20(32):11142-11159.

［54］ Dobosz ?, Stefaniak T, Dobrzycka M, et al. Invasive treatment of pain associated with pancreatic cancer on different levels of WHO analgesic ladder［J］. BMC Surg,2016,16:20.

［55］ Niu L, Wang Y, Yao F, et al. Alleviating visceral cancer pain in patients with pancreatic cancer using cryoablation and celiac plexus block［J］. Cryobiology,2013,66(2):105-111.

［56］ Gupta R, Amanam I, Chung V. Current and future therapies for advanced pancreatic cancer［J］. J Surg Oncol,2017,116(1):25-34.