{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T20:14:44Z","timestamp":1792613684562,"version":"4.5.0"},"reference-count":104,"publisher":"Springer Science and Business Media LLC","issue":"11","license":[{"start":{"date-parts":[[2015,10,13]],"date-time":"2015-10-13T00:00:00Z","timestamp":1444694400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springer.com\/tdm"},{"start":{"date-parts":[[2015,10,13]],"date-time":"2015-10-13T00:00:00Z","timestamp":1444694400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springer.com\/tdm"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Nat Rev Gastroenterol Hepatol"],"published-print":{"date-parts":[[2015,11]]},"DOI":"10.1038\/nrgastro.2015.166","type":"journal-article","created":{"date-parts":[[2015,10,13]],"date-time":"2015-10-13T05:53:45Z","timestamp":1444715625000},"page":"649-659","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":253,"title":["Neural plasticity in pancreatitis and pancreatic cancer"],"prefix":"10.1038","volume":"12","author":[{"given":"Ihsan Ekin","family":"Demir","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helmut","family":"Friess","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G\u00fcralp O.","family":"Ceyhan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2015,10,13]]},"reference":[{"key":"BFnrgastro2015166_CR1","doi-asserted-by":"publisher","first-page":"1626","DOI":"10.1523\/JNEUROSCI.10-05-01626.1990","volume":"10","author":"AL Kirchgessner","year":"1990","unstructured":"Kirchgessner, A. L. & Gershon, M. D. Innervation of the pancreas by neurons in the gut. J. Neurosci. 10, 1626\u20131642 (1990).","journal-title":"J. Neurosci."},{"key":"BFnrgastro2015166_CR2","first-page":"230","volume":"26","author":"AL Kirchgessner","year":"1991","unstructured":"Kirchgessner, A. L. & Gershon, M. D. Innervation and regulation of the pancreas by neurons in the gut. Z. Gastroenterol. Verh. 26, 230\u2013233 (1991).","journal-title":"Z. Gastroenterol. Verh."},{"key":"BFnrgastro2015166_CR3","doi-asserted-by":"publisher","first-page":"270","DOI":"10.1002\/(SICI)1096-9861(19960722)371:2<270::AID-CNE7>3.0.CO;2-#","volume":"371","author":"AL Kirchgessner","year":"1996","unstructured":"Kirchgessner, A. L., Liu, M. T. & Gershon, M. D. In situ identification and visualization of neurons that mediate enteric and enteropancreatic reflexes. J. Comp. Neurol. 371, 270\u2013286 (1996).","journal-title":"J. Comp. Neurol."},{"key":"BFnrgastro2015166_CR4","doi-asserted-by":"publisher","first-page":"1060","DOI":"10.1111\/j.1365-2982.2008.01141.x","volume":"20","author":"AC Schloithe","year":"2008","unstructured":"Schloithe, A. C.  et al. A novel preparation to study rat pancreatic spinal and vagal mechanosensitive afferents in vitro. Neurogastroenterol. Motil. 20, 1060\u20131069 (2008).","journal-title":"Neurogastroenterol. Motil."},{"key":"BFnrgastro2015166_CR5","doi-asserted-by":"publisher","first-page":"938","DOI":"10.1152\/ajpgi.00105.2002","volume":"283","author":"JD Nathan","year":"2002","unstructured":"Nathan, J. D.  et al. Primary sensory neurons: a common final pathway for inflammation in experimental pancreatitis in rats. Am. J. Physiol. Gastrointest. Liver Physiol. 283, 938\u2013946 (2002).","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"BFnrgastro2015166_CR6","doi-asserted-by":"publisher","first-page":"950","DOI":"10.1152\/ajpgi.00549.2004","volume":"288","author":"KN Browning","year":"2005","unstructured":"Browning, K. N., Coleman, F. H. & Travagli, R. A. Characterization of pancreas-projecting rat dorsal motor nucleus of vagus neurons. Am. J. Physiol. Gastrointest. Liver Physiol. 288, 950\u2013955 (2005).","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"BFnrgastro2015166_CR7","doi-asserted-by":"publisher","first-page":"437","DOI":"10.1152\/ajpgi.00402.2012","volume":"304","author":"T Babic","year":"2013","unstructured":"Babic, T.  et al. Role of the vagus in the reduced pancreatic exocrine function in copper-deficient rats. Am. J. Physiol. Gastrointest. Liver Physiol. 304, 437\u2013448 (2013).","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"BFnrgastro2015166_CR8","doi-asserted-by":"publisher","first-page":"18","DOI":"10.1016\/S0006-8993(01)02273-9","volume":"902","author":"X Deng","year":"2001","unstructured":"Deng, X.  et al. The area postrema lesions alter the inhibitory effects of peripherally infused pancreatic polypeptide on pancreatic secretion. Brain Res. 902, 18\u201329 (2001).","journal-title":"Brain Res."},{"key":"BFnrgastro2015166_CR9","doi-asserted-by":"publisher","first-page":"1283","DOI":"10.1053\/j.gastro.2010.12.033","volume":"140","author":"ES Schwartz","year":"2010","unstructured":"Schwartz, E. S.  et al. Synergistic role of TRPV1 and TRPA1 in pancreatic pain and inflammation. Gastroenterology 140, 1283\u20131291.e1\u2013e2 (2010).","journal-title":"Gastroenterology"},{"key":"BFnrgastro2015166_CR10","doi-asserted-by":"publisher","first-page":"551","DOI":"10.1159\/000082180","volume":"4","author":"RA Liddle","year":"2004","unstructured":"Liddle, R. A. & Nathan, J. D. Neurogenic inflammation and pancreatitis. Pancreatology 4, 551\u2013559 (2004).","journal-title":"Pancreatology"},{"key":"BFnrgastro2015166_CR11","doi-asserted-by":"publisher","first-page":"959","DOI":"10.1152\/ajpgi.00154.2005","volume":"290","author":"EC Wick","year":"2006","unstructured":"Wick, E. C.  et al. Transient receptor potential vanilloid 1, calcitonin gene-related peptide, and substance P mediate nociception in acute pancreatitis. Am. J. Physiol. Gastrointest. Liver Physiol. 290, 959\u2013969 (2006).","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"BFnrgastro2015166_CR12","doi-asserted-by":"publisher","first-page":"491","DOI":"10.1007\/s00401-013-1099-4","volume":"125","author":"IE Demir","year":"2013","unstructured":"Demir, I. E.  et al. Neural plasticity in the gastrointestinal tract: chronic inflammation, neurotrophic signals, and hypersensitivity. Acta Neuropathol. 125, 491\u2013509 (2013).","journal-title":"Acta Neuropathol."},{"key":"BFnrgastro2015166_CR13","doi-asserted-by":"publisher","first-page":"1940","DOI":"10.1002\/ar.21033","volume":"292","author":"KH Schafer","year":"2009","unstructured":"Schafer, K. H., Van Ginneken, C. & Copray, S. Plasticity and neural stem cells in the enteric nervous system. Anat. Rec. (Hoboken) 292, 1940\u20131952 (2009).","journal-title":"Anat. Rec. (Hoboken)"},{"key":"BFnrgastro2015166_CR14","doi-asserted-by":"publisher","first-page":"177","DOI":"10.1053\/j.gastro.2008.09.029","volume":"136","author":"GO Ceyhan","year":"2009","unstructured":"Ceyhan, G. O.  et al. Pancreatic neuropathy and neuropathic pain\u2014a comprehensive pathomorphological study of 546 cases. Gastroenterology 136, 177\u2013186.e1 (2009).","journal-title":"Gastroenterology"},{"key":"BFnrgastro2015166_CR15","doi-asserted-by":"publisher","first-page":"682","DOI":"10.1136\/gut.50.5.682","volume":"50","author":"H Friess","year":"2002","unstructured":"Friess, H.  et al. Neural alterations in surgical stage chronic pancreatitis are independent of the underlying aetiology. Gut 50, 682\u2013686 (2002).","journal-title":"Gut"},{"key":"BFnrgastro2015166_CR16","doi-asserted-by":"publisher","first-page":"97","DOI":"10.3389\/fphys.2012.00097","volume":"3","author":"IE Demir","year":"2012","unstructured":"Demir, I. E., Friess, H. & Ceyhan, G. O. Nerve-cancer interactions in the stromal biology of pancreatic cancer. Front. Physiol. 3, 97 (2012).","journal-title":"Front. Physiol."},{"key":"BFnrgastro2015166_CR17","doi-asserted-by":"publisher","first-page":"151","DOI":"10.1007\/s00423-010-0731-1","volume":"396","author":"IE Demir","year":"2011","unstructured":"Demir, I. E.  et al. Pain mechanisms in chronic pancreatitis: of a master and his fire. Langenbecks Arch. Surg. 396, 151\u2013160 (2011).","journal-title":"Langenbecks Arch. Surg."},{"key":"BFnrgastro2015166_CR18","doi-asserted-by":"publisher","first-page":"480","DOI":"10.1111\/j.1365-2982.2009.01428.x","volume":"22","author":"IE Demir","year":"2010","unstructured":"Demir, I. E.  et al. The microenvironment in chronic pancreatitis and pancreatic cancer induces neuronal plasticity. Neurogastroenterol. Motil. 22, 480\u2013490, e112\u2013e113 (2010).","journal-title":"Neurogastroenterol. Motil."},{"key":"BFnrgastro2015166_CR19","doi-asserted-by":"publisher","first-page":"923","DOI":"10.1097\/SLA.0b013e3181d974d4","volume":"251","author":"GO Ceyhan","year":"2010","unstructured":"Ceyhan, G. O.  et al. Nerve growth factor and artemin are paracrine mediators of pancreatic neuropathy in pancreatic adenocarcinoma. Ann. Surg. 251, 923\u2013931 (2010).","journal-title":"Ann. Surg."},{"key":"BFnrgastro2015166_CR20","doi-asserted-by":"publisher","first-page":"1017","DOI":"10.1152\/ajpgi.00517.2011","volume":"303","author":"IE Demir","year":"2012","unstructured":"Demir, I. E.  et al. Neuronal plasticity in chronic pancreatitis is mediated via the neurturin\/GFRalpha2 axis. Am. J. Physiol. Gastrointest. Liver Physiol. 303, 1017\u20131028 (2012).","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"BFnrgastro2015166_CR21","doi-asserted-by":"publisher","first-page":"103","DOI":"10.1093\/carcin\/bgt312","volume":"35","author":"K Wang","year":"2014","unstructured":"Wang, K.  et al. The neurotrophic factor neurturin contributes toward an aggressive cancer cell phenotype, neuropathic pain and neuronal plasticity in pancreatic cancer. Carcinogenesis 35, 103\u2013113 (2014).","journal-title":"Carcinogenesis"},{"key":"BFnrgastro2015166_CR22","doi-asserted-by":"publisher","first-page":"534","DOI":"10.1136\/gut.2006.105528","volume":"56","author":"GO Ceyhan","year":"2007","unstructured":"Ceyhan, G. O.  et al. The neurotrophic factor artemin influences the extent of neural damage and growth in chronic pancreatitis. Gut 56, 534\u2013544 (2007).","journal-title":"Gut"},{"key":"BFnrgastro2015166_CR23","doi-asserted-by":"publisher","first-page":"274","DOI":"10.1097\/01.sla.0000217642.68697.55","volume":"244","author":"GO Ceyhan","year":"2006","unstructured":"Ceyhan, G. O.  et al. The neurotrophic factor artemin promotes pancreatic cancer invasion. Ann. Surg. 244, 274\u2013281 (2006).","journal-title":"Ann. Surg."},{"key":"BFnrgastro2015166_CR24","doi-asserted-by":"publisher","first-page":"347","DOI":"10.1038\/labinvest.2008.170","volume":"89","author":"GO Ceyhan","year":"2009","unstructured":"Ceyhan, G. O.  et al. Neural fractalkine expression is closely linked to pain and pancreatic neuritis in human chronic pancreatitis. Lab. Invest. 89, 347\u2013361 (2009).","journal-title":"Lab. Invest."},{"key":"BFnrgastro2015166_CR25","doi-asserted-by":"publisher","first-page":"e60529","DOI":"10.1371\/journal.pone.0060529","volume":"8","author":"IE Demir","year":"2013","unstructured":"Demir, I. E.  et al. Perineural mast cells are specifically enriched in pancreatic neuritis and neuropathic pain in pancreatic cancer and chronic pancreatitis. PLoS ONE 8, e60529 (2013).","journal-title":"PLoS ONE"},{"key":"BFnrgastro2015166_CR26","doi-asserted-by":"publisher","first-page":"423","DOI":"10.1136\/gut.47.3.423","volume":"47","author":"P Di Sebastiano","year":"2000","unstructured":"Di Sebastiano P.  et al. Expression of interleukin 8 (IL-8) and substance P in human chronic pancreatitis. Gut 47, 423\u2013428 (2000).","journal-title":"Gut"},{"key":"BFnrgastro2015166_CR27","doi-asserted-by":"publisher","first-page":"1648","DOI":"10.1016\/S0016-5085(97)70047-7","volume":"112","author":"P Di Sebastiano","year":"1997","unstructured":"Di Sebastiano, P.  et al. Immune cell infiltration and growth-associated protein 43 expression correlate with pain in chronic pancreatitis. Gastroenterology 112, 1648\u20131655 (1997).","journal-title":"Gastroenterology"},{"key":"BFnrgastro2015166_CR28","doi-asserted-by":"publisher","first-page":"919","DOI":"10.1007\/s00423-007-0277-z","volume":"393","author":"FF di Mola","year":"2008","unstructured":"di Mola, F. F. & di Sebastiano, P. Pain and pain generation in pancreatic cancer. Langenbecks Arch. Surg. 393, 919\u2013922 (2008).","journal-title":"Langenbecks Arch. Surg."},{"key":"BFnrgastro2015166_CR29","doi-asserted-by":"publisher","first-page":"1573","DOI":"10.2174\/138161211796196918","volume":"17","author":"JD Wood","year":"2011","unstructured":"Wood, J. D. Visceral pain: spinal afferents, enteric mast cells, enteric nervous system and stress. Curr. Pharm. Des. 17, 1573\u20131575 (2011).","journal-title":"Curr. Pharm. Des."},{"key":"BFnrgastro2015166_CR30","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1186\/1471-230X-5-8","volume":"5","author":"WA Hoogerwerf","year":"2005","unstructured":"Hoogerwerf, W. A.  et al. The role of mast cells in the pathogenesis of pain in chronic pancreatitis. BMC Gastroenterol. 5, 8 (2005).","journal-title":"BMC Gastroenterol."},{"key":"BFnrgastro2015166_CR31","first-page":"213","volume":"15","author":"O Bauer","year":"2000","unstructured":"Bauer, O. & Razin, E. Mast cell-nerve interactions. News Physiol. Sci. 15, 213\u2013218 (2000).","journal-title":"News Physiol. Sci."},{"key":"BFnrgastro2015166_CR32","doi-asserted-by":"publisher","first-page":"2975","DOI":"10.1073\/pnas.84.9.2975","volume":"84","author":"RH Stead","year":"1987","unstructured":"Stead, R. H.  et al. Intestinal mucosal mast cells in normal and nematode-infected rat intestines are in intimate contact with peptidergic nerves. Proc. Natl Acad. Sci. USA 84, 2975\u20132979 (1987).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"BFnrgastro2015166_CR33","doi-asserted-by":"publisher","first-page":"5983","DOI":"10.4049\/jimmunol.1002244","volume":"186","author":"M Hagiyama","year":"2011","unstructured":"Hagiyama, M.  et al. Enhanced nerve-mast cell interaction by a neuronal short isoform of cell adhesion molecule-1. J. Immunol. 186, 5983\u20135992 (2011).","journal-title":"J. Immunol."},{"key":"BFnrgastro2015166_CR34","doi-asserted-by":"publisher","first-page":"311","DOI":"10.1016\/j.bbi.2011.09.016","volume":"26","author":"D Levy","year":"2012","unstructured":"Levy, D.  et al. Mast cell degranulation distinctly activates trigemino-cervical and lumbosacral pain pathways and elicits widespread tactile pain hypersensitivity. Brain Behav. Immun. 26, 311\u2013317 (2012).","journal-title":"Brain Behav. Immun."},{"key":"BFnrgastro2015166_CR35","doi-asserted-by":"publisher","first-page":"693","DOI":"10.1053\/j.gastro.2003.11.055","volume":"126","author":"G Barbara","year":"2004","unstructured":"Barbara, G.  et al. Activated mast cells in proximity to colonic nerves correlate with abdominal pain in irritable bowel syndrome. Gastroenterology 126, 693\u2013702 (2004).","journal-title":"Gastroenterology"},{"key":"BFnrgastro2015166_CR36","doi-asserted-by":"publisher","first-page":"85","DOI":"10.1016\/j.bbadis.2011.06.004","volume":"1822","author":"S Buhner","year":"2012","unstructured":"Buhner, S. & Schemann, M. Mast cell-nerve axis with a focus on the human gut. Biochim. Biophys. Acta 1822, 85\u201392 (2012).","journal-title":"Biochim. Biophys. Acta"},{"key":"BFnrgastro2015166_CR37","doi-asserted-by":"publisher","first-page":"1513","DOI":"10.3390\/cancers2031513","volume":"2","author":"IE Demir","year":"2010","unstructured":"Demir, I. E.  et al. Neural invasion in pancreatic cancer: the past, present and future. Cancers (Basel) 2, 1513\u20131527 (2010).","journal-title":"Cancers (Basel)"},{"key":"BFnrgastro2015166_CR38","doi-asserted-by":"publisher","first-page":"900","DOI":"10.1097\/SLA.0000000000000968","volume":"260","author":"F Liebl","year":"2014","unstructured":"Liebl, F.  et al. The impact of neural invasion severity in gastrointestinal malignancies: a clinicopathological study. Ann. Surg. 260, 900\u2013908 (2014).","journal-title":"Ann. Surg."},{"key":"BFnrgastro2015166_CR39","first-page":"469","volume":"1","author":"B Liu","year":"2002","unstructured":"Liu, B. & Lu, K. Y. Neural invasion in pancreatic carcinoma. Hepatobiliary Pancreat. Dis. Int. 1, 469\u2013476 (2002).","journal-title":"Hepatobiliary Pancreat. Dis. Int."},{"key":"BFnrgastro2015166_CR40","doi-asserted-by":"publisher","first-page":"50","DOI":"10.1158\/1078-0432.CCR-12-2392","volume":"19","author":"F Liebl","year":"2013","unstructured":"Liebl, F.  et al. The severity of neural invasion is associated with shortened survival in colon cancer. Clin. Cancer Res. 19, 50\u201361 (2013).","journal-title":"Clin. Cancer Res."},{"key":"BFnrgastro2015166_CR41","doi-asserted-by":"publisher","first-page":"442","DOI":"10.1016\/j.bbrc.2008.07.035","volume":"374","author":"GO Ceyhan","year":"2008","unstructured":"Ceyhan, G. O.  et al. Neural invasion in pancreatic cancer: a mutual tropism between neurons and cancer cells. Biochem. Biophys. Res. Commun. 374, 442\u2013447 (2008).","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"BFnrgastro2015166_CR42","doi-asserted-by":"publisher","first-page":"299","DOI":"10.1016\/j.humpath.2006.08.002","volume":"38","author":"H Dai","year":"2007","unstructured":"Dai, H.  et al. Enhanced survival in perineural invasion of pancreatic cancer: an in vitro approach. Hum. Pathol. 38, 299\u2013307 (2007).","journal-title":"Hum. Pathol."},{"key":"BFnrgastro2015166_CR43","doi-asserted-by":"publisher","first-page":"1529","DOI":"10.1158\/0008-5472.CAN-13-1012","volume":"74","author":"A Gohrig","year":"2014","unstructured":"Gohrig, A.  et al. Axon guidance factor SLIT2 inhibits neural invasion and metastasis in pancreatic cancer. Cancer Res. 74, 1529\u20131540 (2014).","journal-title":"Cancer Res."},{"key":"BFnrgastro2015166_CR44","doi-asserted-by":"publisher","first-page":"5733","DOI":"10.1158\/0008-5472.CAN-12-0764","volume":"72","author":"O Cavel","year":"2012","unstructured":"Cavel, O.  et al. Endoneurial macrophages induce perineural invasion of pancreatic cancer cells by secretion of GDNF and activation of RET tyrosine kinase receptor. Cancer Res. 72, 5733\u20135743 (2012).","journal-title":"Cancer Res."},{"key":"BFnrgastro2015166_CR45","doi-asserted-by":"publisher","first-page":"107","DOI":"10.1093\/jnci\/djp456","volume":"102","author":"Z Gil","year":"2010","unstructured":"Gil, Z.  et al. Paracrine regulation of pancreatic cancer cell invasion by peripheral nerves. J. Natl Cancer Inst. 102, 107\u2013118 (2010).","journal-title":"J. Natl Cancer Inst."},{"key":"BFnrgastro2015166_CR46","doi-asserted-by":"publisher","first-page":"2795","DOI":"10.1002\/ijc.27594","volume":"131","author":"A Imoto","year":"2012","unstructured":"Imoto, A.  et al. Neural invasion induces cachexia via astrocytic activation of neural route in pancreatic cancer. Int. J. Cancer 131, 2795\u20132807 (2012).","journal-title":"Int. J. Cancer"},{"key":"BFnrgastro2015166_CR47","doi-asserted-by":"publisher","first-page":"3379","DOI":"10.1002\/cncr.24396","volume":"115","author":"C Liebig","year":"2009","unstructured":"Liebig, C.  et al. Perineural invasion in cancer: a review of the literature. Cancer 115, 3379\u20133391 (2009).","journal-title":"Cancer"},{"key":"BFnrgastro2015166_CR48","doi-asserted-by":"publisher","first-page":"1494","DOI":"10.1158\/1535-7163.MCT-08-0755","volume":"8","author":"I Abiatari","year":"2009","unstructured":"Abiatari, I.  et al. Consensus transcriptome signature of perineural invasion in pancreatic carcinoma. Mol. Cancer Ther. 8, 1494\u20131504 (2009).","journal-title":"Mol. Cancer Ther."},{"key":"BFnrgastro2015166_CR49","doi-asserted-by":"publisher","first-page":"2555","DOI":"10.1038\/ajg.2009.380","volume":"104","author":"GO Ceyhan","year":"2009","unstructured":"Ceyhan, G. O.  et al. Pancreatic neuropathy results in \u201cneural remodeling\u201d and altered pancreatic innervation in chronic pancreatitis and pancreatic cancer. Am. J. Gastroenterol. 104, 2555\u20132565 (2009).","journal-title":"Am. J. Gastroenterol."},{"key":"BFnrgastro2015166_CR50","doi-asserted-by":"publisher","first-page":"311","DOI":"10.1016\/j.bpg.2010.03.001","volume":"24","author":"GO Ceyhan","year":"2010","unstructured":"Ceyhan, G. O.  et al. Fate of nerves in chronic pancreatitis: neural remodeling and pancreatic neuropathy. Best Pract. Res. Clin. Gastroenterol. 24, 311\u2013322 (2010).","journal-title":"Best Pract. Res. Clin. Gastroenterol."},{"key":"BFnrgastro2015166_CR51","doi-asserted-by":"publisher","first-page":"e1592","DOI":"10.1038\/cddis.2014.557","volume":"6","author":"V Secq","year":"2015","unstructured":"Secq, V.  et al. Stromal SLIT2 impacts on pancreatic cancer-associated neural remodeling. Cell Death Dis. 6, e1592 (2015).","journal-title":"Cell Death Dis."},{"key":"BFnrgastro2015166_CR52","doi-asserted-by":"publisher","first-page":"1605","DOI":"10.1056\/NEJMra0901557","volume":"362","author":"M Hidalgo","year":"2010","unstructured":"Hidalgo, M. Pancreatic cancer. N. Engl. J. Med. 362, 1605\u20131617 (2010).","journal-title":"N. Engl. J. Med."},{"key":"BFnrgastro2015166_CR53","doi-asserted-by":"publisher","first-page":"291","DOI":"10.1016\/j.ccr.2007.01.012","volume":"11","author":"C Guerra","year":"2007","unstructured":"Guerra, C.  et al. Chronic pancreatitis is essential for induction of pancreatic ductal adenocarcinoma by K-Ras oncogenes in adult mice. Cancer Cell 11, 291\u2013302 (2007).","journal-title":"Cancer Cell"},{"key":"BFnrgastro2015166_CR54","doi-asserted-by":"publisher","first-page":"629","DOI":"10.1016\/j.pan.2013.05.009","volume":"13","author":"E Tieftrunk","year":"2013","unstructured":"Tieftrunk, E.  et al. Evidence of pancreatic neuropathy and neuropathic pain in hereditary chronic pancreatitis. Pancreatology 13, 629\u2013630 (2013).","journal-title":"Pancreatology"},{"key":"BFnrgastro2015166_CR55","doi-asserted-by":"publisher","first-page":"197","DOI":"10.2174\/157015906778019554","volume":"4","author":"J Huang","year":"2006","unstructured":"Huang, J., Zhang, X. & McNaughton, P. A. Inflammatory pain: the cellular basis of heat hyperalgesia. Curr. Neuropharmacol. 4, 197\u2013206 (2006).","journal-title":"Curr. Neuropharmacol."},{"key":"BFnrgastro2015166_CR56","doi-asserted-by":"publisher","first-page":"104","DOI":"10.1016\/j.pan.2012.02.010","volume":"12","author":"SG Barreto","year":"2012","unstructured":"Barreto, S. G. & Saccone, G. T. Pancreatic nociception\u2014revisiting the physiology and pathophysiology. Pancreatology 12, 104\u2013112 (2012).","journal-title":"Pancreatology"},{"key":"BFnrgastro2015166_CR57","doi-asserted-by":"publisher","first-page":"400","DOI":"10.1097\/ACO.0b013e32834871df","volume":"24","author":"Q Xu","year":"2011","unstructured":"Xu, Q. & Yaksh, T. L. A brief comparison of the pathophysiology of inflammatory versus neuropathic pain. Curr. Opin. Anaesthesiol. 24, 400\u2013407 (2011).","journal-title":"Curr. Opin. Anaesthesiol."},{"key":"BFnrgastro2015166_CR58","doi-asserted-by":"publisher","first-page":"219","DOI":"10.1016\/0016-5085(94)90080-9","volume":"107","author":"DE Bockman","year":"1994","unstructured":"Bockman, D. E., Buchler, M. & Beger, H. G. Interaction of pancreatic ductal carcinoma with nerves leads to nerve damage. Gastroenterology 107, 219\u2013230 (1994).","journal-title":"Gastroenterology"},{"key":"BFnrgastro2015166_CR59","doi-asserted-by":"publisher","first-page":"1459","DOI":"10.1016\/0016-5085(88)90687-7","volume":"94","author":"DE Bockman","year":"1988","unstructured":"Bockman, D. E.  et al. Analysis of nerves in chronic pancreatitis. Gastroenterology 94, 1459\u20131469 (1988).","journal-title":"Gastroenterology"},{"key":"BFnrgastro2015166_CR60","doi-asserted-by":"publisher","first-page":"183","DOI":"10.1097\/00006676-199203000-00009","volume":"7","author":"M Buchler","year":"1992","unstructured":"Buchler, M.  et al. Changes in peptidergic innervation in chronic pancreatitis. Pancreas 7, 183\u2013192 (1992).","journal-title":"Pancreas"},{"key":"BFnrgastro2015166_CR61","doi-asserted-by":"publisher","first-page":"1718","DOI":"10.1158\/0008-5472.CAN-13-2050","volume":"74","author":"RE Stopczynski","year":"2014","unstructured":"Stopczynski, R. E.  et al. Neuroplastic changes occur early in the development of pancreatic ductal adenocarcinoma. Cancer Res. 74, 1718\u20131727 (2014).","journal-title":"Cancer Res."},{"key":"BFnrgastro2015166_CR62","doi-asserted-by":"publisher","first-page":"214","DOI":"10.1016\/j.pain.2005.06.013","volume":"117","author":"JH Winston","year":"2005","unstructured":"Winston, J. H.  et al. Molecular and behavioral changes in nociception in a novel rat model of chronic pancreatitis for the study of pain. Pain 117, 214\u2013222 (2005).","journal-title":"Pain"},{"key":"BFnrgastro2015166_CR63","doi-asserted-by":"publisher","first-page":"1282","DOI":"10.1053\/j.gastro.2007.06.015","volume":"133","author":"GY Xu","year":"2007","unstructured":"Xu, G. Y.  et al. Transient receptor potential vanilloid 1 mediates hyperalgesia and is up-regulated in rats with chronic pancreatitis. Gastroenterology 133, 1282\u20131292 (2007).","journal-title":"Gastroenterology"},{"key":"BFnrgastro2015166_CR64","doi-asserted-by":"publisher","first-page":"176","DOI":"10.1152\/ajpgi.00053.2011","volume":"302","author":"Y Zhu","year":"2012","unstructured":"Zhu, Y.  et al. Systemic administration of anti-NGF increases A-type potassium currents and decreases pancreatic nociceptor excitability in a rat model of chronic pancreatitis. Am. J. Physiol. Gastrointest. Liver Physiol. 302, 176\u2013181 (2012).","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"BFnrgastro2015166_CR65","doi-asserted-by":"publisher","first-page":"424","DOI":"10.1152\/ajpgi.00560.2005","volume":"291","author":"GY Xu","year":"2006","unstructured":"Xu, G. Y.  et al. Enhanced excitability and suppression of A-type K+ current of pancreas-specific afferent neurons in a rat model of chronic pancreatitis. Am. J. Physiol. Gastrointest. Liver Physiol. 291, 424\u2013431 (2006).","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"BFnrgastro2015166_CR66","doi-asserted-by":"publisher","first-page":"615","DOI":"10.1097\/00000658-199911000-00002","volume":"230","author":"H Friess","year":"1999","unstructured":"Friess, H.  et al. Nerve growth factor and its high-affinity receptor in chronic pancreatitis. Ann. Surg. 230, 615\u2013624 (1999).","journal-title":"Ann. Surg."},{"key":"BFnrgastro2015166_CR67","doi-asserted-by":"publisher","first-page":"268","DOI":"10.1097\/01.mpa.0000240600.72946.23","volume":"33","author":"S Takamido","year":"2006","unstructured":"Takamido, S.  et al. Intrapancreatic axonal hyperbranching of dorsal root ganglia neurons in chronic pancreatitis model rats and its relation to pancreatic pain. Pancreas 33, 268\u2013279 (2006).","journal-title":"Pancreas"},{"key":"BFnrgastro2015166_CR68","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1186\/1744-8069-7-15","volume":"7","author":"NS Qian","year":"2011","unstructured":"Qian, N. S.  et al. Spinal toll like receptor 3 is involved in chronic pancreatitis-induced mechanical allodynia of rat. Mol. Pain 7, 15 (2011).","journal-title":"Mol. Pain"},{"key":"BFnrgastro2015166_CR69","doi-asserted-by":"publisher","first-page":"165","DOI":"10.1053\/j.gastro.2011.09.041","volume":"142","author":"PY Liu","year":"2012","unstructured":"Liu, P. Y.  et al. Spinal microglia initiate and maintain hyperalgesia in a rat model of chronic pancreatitis. Gastroenterology 142, 165\u2013173.e2 (2012).","journal-title":"Gastroenterology"},{"key":"BFnrgastro2015166_CR70","doi-asserted-by":"publisher","first-page":"dju184","DOI":"10.1093\/jnci\/dju184","volume":"106","author":"IE Demir","year":"2014","unstructured":"Demir, I. E.  et al. Investigation of Schwann cells at neoplastic cell sites before the onset of cancer invasion. J. Natl Cancer Inst. 106, dju184 (2014).","journal-title":"J. Natl Cancer Inst."},{"key":"BFnrgastro2015166_CR71","doi-asserted-by":"publisher","first-page":"2419","DOI":"10.1158\/1078-0432.CCR-05-1852","volume":"12","author":"N Koide","year":"2006","unstructured":"Koide, N.  et al. Establishment of perineural invasion models and analysis of gene expression revealed an invariant chain (CD74) as a possible molecule involved in perineural invasion in pancreatic cancer. Clin. Cancer Res. 12, 2419\u20132426 (2006).","journal-title":"Clin. Cancer Res."},{"key":"BFnrgastro2015166_CR72","doi-asserted-by":"publisher","first-page":"968","DOI":"10.1038\/ajg.2010.479","volume":"106","author":"T Samkharadze","year":"2011","unstructured":"Samkharadze, T.  et al. Pigment epithelium-derived factor associates with neuropathy and fibrosis in pancreatic cancer. Am. J. Gastroenterol. 106, 968\u2013980 (2011).","journal-title":"Am. J. Gastroenterol."},{"key":"BFnrgastro2015166_CR73","doi-asserted-by":"publisher","first-page":"724","DOI":"10.1016\/j.cgh.2010.03.005","volume":"8","author":"SS Olesen","year":"2010","unstructured":"Olesen, S. S.  et al. Descending inhibitory pain modulation is impaired in patients with chronic pancreatitis. Clin. Gastroenterol. Hepatol. 8, 724\u2013730 (2010).","journal-title":"Clin. Gastroenterol. Hepatol."},{"key":"BFnrgastro2015166_CR74","doi-asserted-by":"publisher","first-page":"418","DOI":"10.1097\/MEG.0b013e3283457b09","volume":"23","author":"SS Olesen","year":"2011","unstructured":"Olesen, S. S.  et al. Slowed EEG rhythmicity in patients with chronic pancreatitis: evidence of abnormal cerebral pain processing? Eur. J. Gastroenterol. Hepatol. 23, 418\u2013424 (2011).","journal-title":"Eur. J. Gastroenterol. Hepatol."},{"key":"BFnrgastro2015166_CR75","doi-asserted-by":"publisher","first-page":"46","DOI":"10.1002\/j.1532-2149.2012.00155.x","volume":"17","author":"SS Olesen","year":"2013","unstructured":"Olesen, S. S.  et al. Cerebral excitability is abnormal in patients with painful chronic pancreatitis. Eur. J. Pain. 17, 46\u201354 (2013).","journal-title":"Eur. J. Pain."},{"key":"BFnrgastro2015166_CR76","doi-asserted-by":"publisher","first-page":"742","DOI":"10.1159\/000321644","volume":"10","author":"SS Olesen","year":"2010","unstructured":"Olesen, S. S.  et al. Pain-associated adaptive cortical reorganisation in chronic pancreatitis. Pancreatology 10, 742\u2013751 (2010).","journal-title":"Pancreatology"},{"key":"BFnrgastro2015166_CR77","doi-asserted-by":"publisher","first-page":"e57963","DOI":"10.1371\/journal.pone.0057963","volume":"8","author":"SS Olesen","year":"2013","unstructured":"Olesen, S. S.  et al. Quantitative sensory testing predicts pregabalin efficacy in painful chronic pancreatitis. PLoS ONE 8, e57963 (2013).","journal-title":"PLoS ONE"},{"key":"BFnrgastro2015166_CR78","doi-asserted-by":"publisher","first-page":"878","DOI":"10.1111\/j.1365-2036.2011.04802.x","volume":"34","author":"SS Olesen","year":"2013","unstructured":"Olesen, S. S.  et al. Randomised clinical trial: pregabalin attenuates experimental visceral pain through sub-cortical mechanisms in patients with painful chronic pancreatitis. Aliment. Pharmacol. Ther. 34, 878\u2013887 (2013).","journal-title":"Aliment. Pharmacol. Ther."},{"key":"BFnrgastro2015166_CR79","doi-asserted-by":"publisher","first-page":"363","DOI":"10.1016\/j.ejpain.2005.06.006","volume":"10","author":"HC Buscher","year":"2006","unstructured":"Buscher, H. C., Wilder-Smith, O. H. & van Goor, H. Chronic pancreatitis patients show hyperalgesia of central origin: a pilot study. Eur. J. Pain 10, 363\u2013370 (2006).","journal-title":"Eur. J. Pain"},{"key":"BFnrgastro2015166_CR80","doi-asserted-by":"publisher","first-page":"815","DOI":"10.2147\/JPR.S50919","volume":"6","author":"M de Vries","year":"2013","unstructured":"de Vries, M.  et al. Altered resting state EEG in chronic pancreatitis patients: toward a marker for chronic pain. J. Pain Res. 6, 815\u2013824 (2013).","journal-title":"J. Pain Res."},{"key":"BFnrgastro2015166_CR81","doi-asserted-by":"publisher","first-page":"363","DOI":"10.1111\/j.1365-2125.2011.04104.x","volume":"73","author":"C Graversen","year":"2012","unstructured":"Graversen, C.  et al. The analgesic effect of pregabalin in patients with chronic pain is reflected by changes in pharmaco-EEG spectral indices. Br. J. Clin. Pharmacol. 73, 363\u2013372 (2012).","journal-title":"Br. J. Clin. Pharmacol."},{"key":"BFnrgastro2015166_CR82","doi-asserted-by":"publisher","first-page":"968","DOI":"10.1002\/j.1532-2149.2013.00442.x","volume":"18","author":"D Lelic","year":"2014","unstructured":"Lelic, D.  et al. Functional reorganization of brain networks in patients with painful chronic pancreatitis. Eur. J. Pain 18, 968\u2013977 (2014).","journal-title":"Eur. J. Pain"},{"key":"BFnrgastro2015166_CR83","doi-asserted-by":"publisher","first-page":"1554","DOI":"10.1136\/gut.2010.236620","volume":"60","author":"JB Frokjaer","year":"2011","unstructured":"Frokjaer, J. B.  et al. Altered brain microstructure assessed by diffusion tensor imaging in patients with chronic pancreatitis. Gut 60, 1554\u20131562 (2011).","journal-title":"Gut"},{"key":"BFnrgastro2015166_CR84","doi-asserted-by":"publisher","first-page":"434","DOI":"10.1016\/j.cgh.2011.11.024","volume":"10","author":"JB Frokjaer","year":"2012","unstructured":"Frokjaer, J. B.  et al. Reduced cortical thickness of brain areas involved in pain processing in patients with chronic pancreatitis. Clin. Gastroenterol. Hepatol. 10, 434\u2013438.e1 (2012).","journal-title":"Clin. Gastroenterol. Hepatol."},{"key":"BFnrgastro2015166_CR85","first-page":"26","volume":"3","author":"B Salvioli","year":"2002","unstructured":"Salvioli, B.  et al. Neurology and neuropathology of the pancreatic innervation. JOP 3, 26\u201333 (2002).","journal-title":"JOP"},{"key":"BFnrgastro2015166_CR86","doi-asserted-by":"publisher","first-page":"10222","DOI":"10.1158\/0008-5472.CAN-06-2483","volume":"67","author":"BJ Swanson","year":"2007","unstructured":"Swanson, B. J.  et al. MUC1 is a counter-receptor for myelin-associated glycoprotein (Siglec-4a) and their interaction contributes to adhesion in pancreatic cancer perineural invasion. Cancer Res. 67, 10222\u201310229 (2007).","journal-title":"Cancer Res."},{"key":"BFnrgastro2015166_CR87","doi-asserted-by":"publisher","first-page":"1361","DOI":"10.1038\/nn1992","volume":"10","author":"J Scholz","year":"2007","unstructured":"Scholz, J. & Woolf, C. J. The neuropathic pain triad: neurons, immune cells and glia. Nat. Neurosci. 10, 1361\u20131368 (2007).","journal-title":"Nat. Neurosci."},{"key":"BFnrgastro2015166_CR88","doi-asserted-by":"publisher","first-page":"1236361","DOI":"10.1126\/science.1236361","volume":"341","author":"C Magnon","year":"2013","unstructured":"Magnon, C.  et al. Autonomic nerve development contributes to prostate cancer progression. Science 341, 1236361 (2013).","journal-title":"Science"},{"key":"BFnrgastro2015166_CR89","doi-asserted-by":"publisher","first-page":"250ra115","DOI":"10.1126\/scitranslmed.3009569","volume":"6","author":"CM Zhao","year":"2014","unstructured":"Zhao, C. M.  et al. Denervation suppresses gastric tumorigenesis. Sci. Transl. Med. 6, 250ra115 (2014).","journal-title":"Sci. Transl. Med."},{"key":"BFnrgastro2015166_CR90","doi-asserted-by":"publisher","first-page":"1777","DOI":"10.1158\/0008-5472.CAN-14-3180","volume":"75","author":"P Jobling","year":"2015","unstructured":"Jobling, P.  et al. Nerve-cancer cell cross-talk: a novel promoter of tumor progression. Cancer Res. 75, 1777\u20131781 (2015).","journal-title":"Cancer Res."},{"key":"BFnrgastro2015166_CR91","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1159\/000100045","volume":"39","author":"HM Schuller","year":"2007","unstructured":"Schuller, H. M. Neurotransmitter receptor-mediated signaling pathways as modulators of carcinogenesis. Prog. Exp. Tumor Res. 39, 45\u201363 (2007).","journal-title":"Prog. Exp. Tumor Res."},{"key":"BFnrgastro2015166_CR92","doi-asserted-by":"publisher","first-page":"188","DOI":"10.1002\/ijc.2910440134","volume":"44","author":"M Tatsuta","year":"1989","unstructured":"Tatsuta, M., Iishi, H. & Baba, M. Inhibition by neostigmine and isoproterenol and promotion by atropine of experimental carcinogenesis in rat stomach by N methyl N' nitro N-nitrosoguanidine. Int. J. Cancer 44, 188\u2013189 (1989).","journal-title":"Int. J. Cancer"},{"key":"BFnrgastro2015166_CR93","first-page":"4199","volume":"49","author":"M Tatsuta","year":"1989","unstructured":"Tatsuta, M.  et al. Effect of 6-hydroxydopamine on gastric carcinogenesis and tetragastrin inhibition of gastric carcinogenesis induced by N methyl N' nitro N-nitrosoguanidine in Wistar rats. Cancer Res. 49, 4199\u20134203 (1989).","journal-title":"Cancer Res."},{"key":"BFnrgastro2015166_CR94","doi-asserted-by":"publisher","first-page":"767","DOI":"10.1002\/ijc.2910510517","volume":"51","author":"M Tatsuta","year":"1992","unstructured":"Tatsuta, M.  et al. Inhibitions by 6-hydroxydopamine and neostigmine singly or together of gastric carcinogenesis induced by N methyl N' nitro N-nitrosoguanidine in Wistar rats. Int. J. Cancer 51, 767\u2013771 (1992).","journal-title":"Int. J. Cancer"},{"key":"BFnrgastro2015166_CR95","doi-asserted-by":"publisher","first-page":"773","DOI":"10.1038\/bjc.1990.377","volume":"62","author":"M Tatsuta","year":"1990","unstructured":"Tatsuta, M.  et al. Inhibition by neostigmine of hepatocarcinogenesis induced by N-nitrosomorpholine in Sprague-Dawley rats. Br. J. Cancer 62, 773\u2013775 (1990).","journal-title":"Br. J. Cancer"},{"key":"BFnrgastro2015166_CR96","doi-asserted-by":"publisher","first-page":"619","DOI":"10.1038\/bjc.1988.271","volume":"58","author":"M Tatsuta","year":"1988","unstructured":"Tatsuta, M.  et al. Inhibition by isoproterenol and neostigmine of experimental carcinogenesis in rat colon by azoxymethane. Br. J. Cancer 58, 619\u2013620 (1988).","journal-title":"Br. J. Cancer"},{"key":"BFnrgastro2015166_CR97","doi-asserted-by":"publisher","first-page":"477","DOI":"10.1097\/CAD.0b013e32832bd1e3","volume":"20","author":"HA Al-Wadei","year":"2009","unstructured":"Al-Wadei, H. A., Al-Wadei, M. H. & Schuller, H. M. Prevention of pancreatic cancer by the beta-blocker propranolol. Anticancer Drugs 20, 477\u2013482 (2009).","journal-title":"Anticancer Drugs"},{"key":"BFnrgastro2015166_CR98","first-page":"874","volume":"123","author":"S Hassan","year":"2014","unstructured":"Hassan, S.  et al. Behavioral stress accelerates prostate cancer development in mice. J. Clin. Invest. 123, 874\u2013886 (2014).","journal-title":"J. Clin. Invest."},{"key":"BFnrgastro2015166_CR99","doi-asserted-by":"publisher","first-page":"939","DOI":"10.1038\/nm1447","volume":"12","author":"PH Thaker","year":"2006","unstructured":"Thaker, P. H.  et al. Chronic stress promotes tumor growth and angiogenesis in a mouse model of ovarian carcinoma. Nat. Med. 12, 939\u2013944 (2006).","journal-title":"Nat. Med."},{"key":"BFnrgastro2015166_CR100","doi-asserted-by":"publisher","first-page":"1515","DOI":"10.1172\/JCI40802","volume":"120","author":"AK Sood","year":"2010","unstructured":"Sood, A. K.  et al. Adrenergic modulation of focal adhesion kinase protects human ovarian cancer cells from anoikis. J. Clin. Invest. 120, 1515\u20131523 (2010).","journal-title":"J. Clin. Invest."},{"key":"BFnrgastro2015166_CR101","doi-asserted-by":"publisher","first-page":"400","DOI":"10.1016\/j.stem.2015.02.006","volume":"16","author":"SC Peterson","year":"2015","unstructured":"Peterson, S. C.  et al. Basal cell carcinoma preferentially arises from stem cells within hair follicle and mechanosensory niches. Cell Stem Cell 16, 400\u2013412 (2015).","journal-title":"Cell Stem Cell"},{"key":"BFnrgastro2015166_CR102","doi-asserted-by":"publisher","first-page":"5133","DOI":"10.7314\/APJCP.2013.14.9.5133","volume":"14","author":"JF Zhang","year":"2013","unstructured":"Zhang, J. F.  et al. Influence of perineural invasion on survival and recurrence in patients with resected pancreatic cancer. Asian Pac. J. Cancer Prev. 14, 5133\u20135139 (2013).","journal-title":"Asian Pac. J. Cancer Prev."},{"key":"BFnrgastro2015166_CR103","first-page":"9154","volume":"20","author":"JG D'Haese","year":"2014","unstructured":"D'Haese, J. G.  et al. Pain sensation in pancreatic diseases is not uniform: the different facets of pancreatic pain. World J. Gastroenterol. 20, 9154\u20139161 (2014).","journal-title":"World J. Gastroenterol."},{"key":"BFnrgastro2015166_CR104","doi-asserted-by":"publisher","first-page":"1373","DOI":"10.1053\/gast.2000.19264","volume":"119","author":"H Toma","year":"2000","unstructured":"Toma, H.  et al. Nerve growth factor expression is up-regulated in the rat model of L arginine induced acute pancreatitis. Gastroenterology 119, 1373\u20131381 (2000).","journal-title":"Gastroenterology"}],"container-title":["Nature Reviews Gastroenterology &amp; Hepatology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/nrgastro.2015.166","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/nrgastro.2015.166.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/nrgastro.2015.166.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,19]],"date-time":"2022-04-19T03:26:27Z","timestamp":1650338787000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/nrgastro.2015.166"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,10,13]]},"references-count":104,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2015,11]]}},"alternative-id":["BFnrgastro2015166"],"URL":"https:\/\/doi.org\/10.1038\/nrgastro.2015.166","relation":{},"ISSN":["1759-5045","1759-5053"],"issn-type":[{"value":"1759-5045","type":"print"},{"value":"1759-5053","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,10,13]]},"assertion":[{"value":"13 October 2015","order":1,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing financial interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}