{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,16]],"date-time":"2026-02-16T10:06:51Z","timestamp":1771236411041,"version":"3.50.1"},"reference-count":31,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2019,12,1]],"date-time":"2019-12-01T00:00:00Z","timestamp":1575158400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2019,12,19]],"date-time":"2019-12-19T00:00:00Z","timestamp":1576713600000},"content-version":"vor","delay-in-days":18,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["81770540"],"award-info":[{"award-number":["81770540"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100017592","name":"Key Science and Technology Program of Shaanxi Province","doi-asserted-by":"crossref","award":["2015SF011"],"award-info":[{"award-number":["2015SF011"]}],"id":[{"id":"10.13039\/501100017592","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Gastroenterol"],"published-print":{"date-parts":[[2019,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n<jats:title>Background<\/jats:title>\n<jats:p>Nerve growth factor (NGF) and enteric glial cells (EGCs) are associated with visceral hypersensitivity and gastrointestinal motility disorder, which may represent the pathogenesis of functional dyspepsia (FD). This study aimed to investigate the expression of NGF, its high affinity receptor tropomyosin receptor kinase A (TrkA) and the EGC activation marker glial fibrillary acidic protein (GFAP) in the gastric mucosa of patients with FD and the association of these proteins with dyspeptic symptoms.<\/jats:p>\n<\/jats:sec><jats:sec>\n<jats:title>Methods<\/jats:title>\n<jats:p>Gastric mucosal biopsies taken from 27 FD patients (9 epigastric pain syndrome (EPS) patients, 7 postprandial distress syndrome (PDS) patients and 11 EPS overlap PDS patients) and 26 control subjects were used for analysis. The expression of NGF, TrkA and GFAP was examined, and the association of these proteins with dyspeptic symptoms, including epigastric pain, postprandial fullness, early satiation and epigastric burning, was analysed.<\/jats:p>\n<\/jats:sec><jats:sec>\n<jats:title>Results<\/jats:title>\n<jats:p>The expression levels of NGF, TrkA, and GFAP in the gastric mucosa were significantly higher in the EPS group, the PDS group, and the EPS overlap PDS group than in the healthy control group. There was no significant difference between the FD subgroups. TrkA colocalized with GFAP, which indicated that TrkA was localized to EGCs, and the expression of TrkA in EGCs was significantly higher in the FD group than in the control group. Changes in the expression of NGF, TrkA, and GFAP were positively correlated with epigastric pain, postprandial fullness and early satiation but had no significant relationship with epigastric burning.<\/jats:p>\n<\/jats:sec><jats:sec>\n<jats:title>Conclusions<\/jats:title>\n<jats:p>The increased expression of gastric NGF, TrkA and GFAP might be involved in FD pathophysiology and symptom perception.<\/jats:p>\n<\/jats:sec>","DOI":"10.1186\/s12876-019-1133-7","type":"journal-article","created":{"date-parts":[[2019,12,19]],"date-time":"2019-12-19T17:04:25Z","timestamp":1576775065000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Nerve growth factor and Tropomyosin receptor kinase A are increased in the gastric mucosa of patients with functional dyspepsia"],"prefix":"10.1186","volume":"19","author":[{"given":"Haitao","family":"Shi","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shanshan","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bin","family":"Qin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lianli","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Juan","family":"Yang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guolong","family":"Lu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fei","family":"Dai","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2019,12,19]]},"reference":[{"issue":"5","key":"1133_CR1","doi-asserted-by":"publisher","first-page":"1466","DOI":"10.1053\/j.gastro.2005.11.059","volume":"130","author":"J Tack","year":"2006","unstructured":"Tack J, Talley NJ, Camilleri M, Holtmann G, Hu P, Malagelada JR, Stanghellini V. Functional gastroduodenal disorders. Gastroenterology. 2006;130(5):1466\u201379.","journal-title":"Gastroenterology"},{"issue":"6","key":"1133_CR2","doi-asserted-by":"publisher","first-page":"1380","DOI":"10.1053\/j.gastro.2016.02.011","volume":"150","author":"V Stanghellini","year":"2016","unstructured":"Stanghellini V, Chan FK, Hasler WL, Malagelada JR, Suzuki H, Tack J, Talley NJ. Gastroduodenal Disorders. Gastroenterology. 2016;150(6):1380\u201392.","journal-title":"Gastroenterology"},{"issue":"17","key":"1133_CR3","doi-asserted-by":"publisher","first-page":"2661","DOI":"10.3748\/wjg.v12.i17.2661","volume":"12","author":"S Mahadeva","year":"2006","unstructured":"Mahadeva S, Goh KL. Epidemiology of functional dyspepsia: a global perspective. World J Gastroenterol. 2006;12(17):2661\u20136.","journal-title":"World J Gastroenterol"},{"issue":"2","key":"1133_CR4","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1159\/000205740","volume":"79","author":"T Shindo","year":"2009","unstructured":"Shindo T, Futagami S, Hiratsuka T, Horie A, Hamamoto T, Ueki N, Kusunoki M, Miyake K, Gudis K, Tsukui T, et al. Comparison of gastric emptying and plasma ghrelin levels in patients with functional dyspepsia and non-erosive reflux disease. Digestion. 2009;79(2):65\u201372.","journal-title":"Digestion"},{"issue":"3","key":"1133_CR5","doi-asserted-by":"publisher","first-page":"526","DOI":"10.1053\/gast.2001.27180","volume":"121","author":"J Tack","year":"2001","unstructured":"Tack J, Caenepeel P, Fischler B, Piessevaux H, Janssens J. Symptoms associated with hypersensitivity to gastric distention in functional dyspepsia. Gastroenterology. 2001;121(3):526\u201335.","journal-title":"Gastroenterology"},{"issue":"5","key":"1133_CR6","doi-asserted-by":"publisher","first-page":"286","DOI":"10.1038\/nrgastro.2012.32","volume":"9","author":"JB Furness","year":"2012","unstructured":"Furness JB. The enteric nervous system and neurogastroenterology. Nat Rev Gastroenterol Hepatol. 2012;9(5):286\u201394.","journal-title":"Nat Rev Gastroenterol Hepatol"},{"issue":"5","key":"1133_CR7","doi-asserted-by":"publisher","first-page":"637","DOI":"10.1586\/egh.10.51","volume":"4","author":"SA Snoek","year":"2010","unstructured":"Snoek SA, Verstege MI, Boeckxstaens GE, van den Wijngaard RM, de Jonge WJ. The enteric nervous system as a regulator of intestinal epithelial barrier function in health and disease. Expert Rev Gastroenterol Hepatol. 2010;4(5):637\u201351.","journal-title":"Expert Rev Gastroenterol Hepatol"},{"issue":"10","key":"1133_CR8","doi-asserted-by":"publisher","first-page":"1252","DOI":"10.1016\/j.humpath.2006.04.027","volume":"37","author":"G Bassotti","year":"2006","unstructured":"Bassotti G, Villanacci V, Cathomas G, Maurer CA, Fisogni S, Cadei M, Baron L, Morelli A, Valloncini E, Salerni B. Enteric neuropathology of the terminal ileum in patients with intractable slow-transit constipation. Hum Pathol. 2006;37(10):1252\u20138.","journal-title":"Hum Pathol"},{"issue":"2","key":"1133_CR9","doi-asserted-by":"publisher","first-page":"e89881","DOI":"10.1371\/journal.pone.0089881","volume":"9","author":"DV Bohorquez","year":"2014","unstructured":"Bohorquez DV, Samsa LA, Roholt A, Medicetty S, Chandra R, Liddle RA. An enteroendocrine cell-enteric glia connection revealed by 3D electron microscopy. PLoS One. 2014;9(2):e89881.","journal-title":"PLoS One"},{"key":"1133_CR10","doi-asserted-by":"publisher","first-page":"6","DOI":"10.1186\/1471-230X-12-6","volume":"12","author":"M Steinkamp","year":"2012","unstructured":"Steinkamp M, Gundel H, Schulte N, Spaniol U, Pflueger C, Zizer E, von Boyen GB. GDNF protects enteric glia from apoptosis: evidence for an autocrine loop. BMC Gastroenterol. 2012;12:6.","journal-title":"BMC Gastroenterol"},{"issue":"11","key":"1133_CR11","doi-asserted-by":"publisher","first-page":"820","DOI":"10.1111\/j.1365-2826.2006.01478.x","volume":"18","author":"GB von Boyen","year":"2006","unstructured":"von Boyen GB, Steinkamp M, Reinshagen M, Schafer KH, Adler G, Kirsch J. Nerve growth factor secretion in cultured enteric glia cells is modulated by proinflammatory cytokines. J Neuroendocrinol. 2006;18(11):820\u20135.","journal-title":"J Neuroendocrinol"},{"issue":"3","key":"1133_CR12","doi-asserted-by":"publisher","first-page":"R235","DOI":"10.1152\/ajpregu.00342.2015","volume":"310","author":"Q Li","year":"2016","unstructured":"Li Q, Winston JH, Sarna SK. Noninflammatory upregulation of nerve growth factor underlies gastric hypersensitivity induced by neonatal colon inflammation. Am J Physiol Regul Integr Comp Physiol. 2016;310(3):R235\u201342.","journal-title":"Am J Physiol Regul Integr Comp Physiol"},{"issue":"2 Suppl","key":"1133_CR13","doi-asserted-by":"publisher","first-page":"S7","DOI":"10.1097\/00002508-200006001-00003","volume":"16","author":"SC Apfel","year":"2000","unstructured":"Apfel SC. Neurotrophic factors and pain. Clin J Pain. 2000;16(2 Suppl):S7\u201311.","journal-title":"Clin J Pain"},{"issue":"3","key":"1133_CR14","doi-asserted-by":"publisher","first-page":"240","DOI":"10.1097\/AJP.0b013e3182048481","volume":"27","author":"RK Gerber","year":"2011","unstructured":"Gerber RK, Nie H, Arendt-Nielsen L, Curatolo M, Graven-Nielsen T. Local pain and spreading hyperalgesia induced by intramuscular injection of nerve growth factor are not reduced by local anesthesia of the muscle. Clin J Pain. 2011;27(3):240\u20137.","journal-title":"Clin J Pain"},{"issue":"4","key":"1133_CR15","doi-asserted-by":"publisher","first-page":"469","DOI":"10.1002\/j.1532-2149.2012.00202.x","volume":"17","author":"CD Mills","year":"2013","unstructured":"Mills CD, Nguyen T, Tanga FY, Zhong C, Gauvin DM, Mikusa J, Gomez EJ, Salyers AK, Bannon AW. Characterization of nerve growth factor-induced mechanical and thermal hypersensitivity in rats. Eur J Pain. 2013;17(4):469\u201379.","journal-title":"Eur J Pain"},{"issue":"3","key":"1133_CR16","doi-asserted-by":"publisher","first-page":"489","DOI":"10.1016\/S0304-3959(03)00266-5","volume":"105","author":"L Delafoy","year":"2003","unstructured":"Delafoy L, Raymond F, Doherty AM, Eschalier A, Diop L. Role of nerve growth factor in the trinitrobenzene sulfonic acid-induced colonic hypersensitivity. Pain. 2003;105(3):489\u201397.","journal-title":"Pain"},{"issue":"2","key":"1133_CR17","doi-asserted-by":"publisher","first-page":"524","DOI":"10.1053\/j.gastro.2004.05.019","volume":"127","author":"F Barreau","year":"2004","unstructured":"Barreau F, Cartier C, Ferrier L, Fioramonti J, Bueno L. Nerve growth factor mediates alterations of colonic sensitivity and mucosal barrier induced by neonatal stress in rats. Gastroenterology. 2004;127(2):524\u201334.","journal-title":"Gastroenterology"},{"key":"1133_CR18","doi-asserted-by":"publisher","first-page":"20320","DOI":"10.1038\/srep20320","volume":"6","author":"P Wang","year":"2016","unstructured":"Wang P, Du C, Chen FX, Li CQ, Yu YB, Han T, Akhtar S, Zuo XL, Tan XD, Li YQ. BDNF contributes to IBS-like colonic hypersensitivity via activating the enteroglia-nerve unit. Sci Rep. 2016;6:20320.","journal-title":"Sci Rep"},{"issue":"3","key":"1133_CR19","doi-asserted-by":"publisher","first-page":"570","DOI":"10.1053\/j.gastro.2012.11.001","volume":"144","author":"JH Winston","year":"2013","unstructured":"Winston JH, Sarna SK. Developmental origins of functional dyspepsia-like gastric hypersensitivity in rats. Gastroenterology. 2013;144(3):570\u20139 e573.","journal-title":"Gastroenterology"},{"issue":"4","key":"1133_CR20","doi-asserted-by":"publisher","first-page":"496","DOI":"10.1007\/s11596-013-1148-1","volume":"33","author":"R Qi","year":"2013","unstructured":"Qi R, Yang W, Chen J. Role of enteric glial cells in gastric motility in diabetic rats at different stages. J Huazhong Univ Sci Technolog Med Sci. 2013;33(4):496\u2013500.","journal-title":"J Huazhong Univ Sci Technolog Med Sci"},{"issue":"8","key":"1133_CR21","doi-asserted-by":"publisher","first-page":"734","DOI":"10.1111\/j.1365-2982.2012.01933.x","volume":"24","author":"S Willot","year":"2012","unstructured":"Willot S, Gauthier C, Patey N, Faure C. Nerve growth factor content is increased in the rectal mucosa of children with diarrhea-predominant irritable bowel syndrome. Neurogastroenterol Motil. 2012;24(8):734\u20139 e347.","journal-title":"Neurogastroenterol Motil"},{"issue":"5","key":"1133_CR22","doi-asserted-by":"publisher","first-page":"1002","DOI":"10.1053\/j.gastro.2015.01.042","volume":"148","author":"G Dothel","year":"2015","unstructured":"Dothel G, Barbaro MR, Boudin H, Vasina V, Cremon C, Gargano L, Bellacosa L, De Giorgio R, Le Berre-Scoul C, Aubert P, et al. Nerve fiber outgrowth is increased in the intestinal mucosa of patients with irritable bowel syndrome. Gastroenterology. 2015;148(5):1002\u201311 e1004.","journal-title":"Gastroenterology"},{"key":"1133_CR23","doi-asserted-by":"publisher","first-page":"251","DOI":"10.1007\/978-3-642-45106-5_10","volume":"220","author":"GR Lewin","year":"2014","unstructured":"Lewin GR, Lechner SG, Smith ES. Nerve growth factor and nociception: from experimental embryology to new analgesic therapy. Handb Exp Pharmacol. 2014;220:251\u201382.","journal-title":"Handb Exp Pharmacol"},{"issue":"6","key":"1133_CR24","doi-asserted-by":"publisher","first-page":"814","DOI":"10.1136\/gut.42.6.814","volume":"42","author":"H Mertz","year":"1998","unstructured":"Mertz H, Fullerton S, Naliboff B, Mayer EA. Symptoms and visceral perception in severe functional and organic dyspepsia. Gut. 1998;42(6):814\u201322.","journal-title":"Gut"},{"issue":"3","key":"1133_CR25","doi-asserted-by":"publisher","first-page":"G499","DOI":"10.1152\/ajpgi.00356.2002","volume":"284","author":"K Bielefeldt","year":"2003","unstructured":"Bielefeldt K, Ozaki N, Gebhart GF. Role of nerve growth factor in modulation of gastric afferent neurons in the rat. Am J Physiol Gastrointest Liver Physiol. 2003;284(3):G499\u2013507.","journal-title":"Am J Physiol Gastrointest Liver Physiol"},{"issue":"5","key":"1133_CR26","doi-asserted-by":"publisher","first-page":"670","DOI":"10.1136\/gut.46.5.670","volume":"46","author":"FF di Mola","year":"2000","unstructured":"di Mola FF, Friess H, Zhu ZW, Koliopanos A, Bley T, Di Sebastiano P, Innocenti P, Zimmermann A, Buchler MW. Nerve growth factor and Trk high affinity receptor (TrkA) gene expression in inflammatory bowel disease. Gut. 2000;46(5):670\u20139.","journal-title":"Gut"},{"issue":"5","key":"1133_CR27","doi-asserted-by":"publisher","first-page":"R1322","DOI":"10.1152\/ajpregu.00066.2003","volume":"284","author":"M Reinshagen","year":"2003","unstructured":"Reinshagen M, Steinkamp M. NGF---not just a nerve growth factor in the gut. Am J Physiol Regul Integr Comp Physiol. 2003;284(5):R1322.","journal-title":"Am J Physiol Regul Integr Comp Physiol"},{"issue":"8","key":"1133_CR28","doi-asserted-by":"publisher","first-page":"1205","DOI":"10.1038\/ajg.2015.158","volume":"110","author":"C Cirillo","year":"2015","unstructured":"Cirillo C, Bessissow T, Desmet AS, Vanheel H, Tack J, Vanden Berghe P. Evidence for neuronal and structural changes in submucous ganglia of patients with functional dyspepsia. Am J Gastroenterol. 2015;110(8):1205\u201315.","journal-title":"Am J Gastroenterol"},{"issue":"6","key":"1133_CR29","doi-asserted-by":"publisher","first-page":"777","DOI":"10.1111\/j.1365-2982.2005.00687.x","volume":"17","author":"A Ruhl","year":"2005","unstructured":"Ruhl A. Glial cells in the gut. Neurogastroenterol Motil. 2005;17(6):777\u201390.","journal-title":"Neurogastroenterol Motil"},{"issue":"1","key":"1133_CR30","doi-asserted-by":"publisher","first-page":"176","DOI":"10.1053\/j.gastro.2013.09.030","volume":"146","author":"B Stoffels","year":"2014","unstructured":"Stoffels B, Hupa KJ, Snoek SA, van Bree S, Stein K, Schwandt T, Vilz TO, Lysson M, Veer CV, Kummer MP, et al. Postoperative ileus involves interleukin-1 receptor signaling in enteric glia. Gastroenterology. 2014;146(1):176\u201387 e171.","journal-title":"Gastroenterology"},{"issue":"32","key":"1133_CR31","doi-asserted-by":"publisher","first-page":"11273","DOI":"10.3748\/wjg.v20.i32.11273","volume":"20","author":"YB Yu","year":"2014","unstructured":"Yu YB, Li YQ. Enteric glial cells and their role in the intestinal epithelial barrier. World J Gastroenterol. 2014;20(32):11273\u201380.","journal-title":"World J Gastroenterol"}],"container-title":["BMC Gastroenterology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/s12876-019-1133-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/article\/10.1186\/s12876-019-1133-7\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/s12876-019-1133-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,12,18]],"date-time":"2020-12-18T00:18:45Z","timestamp":1608250725000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmcgastroenterol.biomedcentral.com\/articles\/10.1186\/s12876-019-1133-7"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,12]]},"references-count":31,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2019,12]]}},"alternative-id":["1133"],"URL":"https:\/\/doi.org\/10.1186\/s12876-019-1133-7","relation":{},"ISSN":["1471-230X"],"issn-type":[{"value":"1471-230X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,12]]},"assertion":[{"value":"24 March 2019","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"2 December 2019","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"19 December 2019","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The study was approved by the Ethics Committee of The Second Affiliated Hospital of Xi\u2019an Jiaotong University. The written informed consent was obtained from each participant.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not Applicable.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that they have no competing interests.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"221"}}