{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T12:16:16Z","timestamp":1792066576347,"version":"4.4.0"},"reference-count":155,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2024,2,23]],"date-time":"2024-02-23T00:00:00Z","timestamp":1708646400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Life"],"abstract":"<jats:p>The intricate network of the pancreatic nervous system plays a fundamental role in physiologic functions of the endocrine and exocrine pancreas. Several pancreatic diseases affect the normal functionality of the pancreatic nervous system. This chronic derangement leads to anatomical alterations, such as neural hypertrophy and increased nerve density. Perineural invasion is a prominent feature of pancreatic cancer, contributing to cancer progression and metastasis. Despite the fact that these pathogenic mechanisms are still incompletely studied and understood, the constant occurrence of these alterations highlights their importance in the pathophysiology of the pancreatic diseases. The occurrence of anatomical changes is strictly linked to the appearance of pain. Pancreatic pain has peculiar features, and its management is complex in clinical practice. In the present review, the evidence on lifestyle, pharmacological and interventional approaches for the management of pancreatic pain is presented. Analgesic therapy is the cornerstone of pain treatment. However, it is important to identify the individual characteristic of the patients and personalize the approach to pain management. Nevertheless, the incomplete efficacy of these strategies makes this field an area of unmet needs. The study of neuroplasticity is crucial to understand the mechanisms that regulate the pathophysiology of pancreatic diseases. Several trials testing new drugs with specific neuromodulatory effects are ongoing. However, further studies are needed to investigate crucial targets to develop novel therapies for the modulation of the nervous system and the prevention of complications of pancreatic diseases. This comprehensive review summarizes the importance of the nervous system in pancreatic diseases with a special focus on its anatomy and physiology, its pathophysiological features and clinical relevance in pancreatic disease, the treatment of pancreatic pain, and the identification of future trends of research.<\/jats:p>","DOI":"10.3390\/life14030299","type":"journal-article","created":{"date-parts":[[2024,2,23]],"date-time":"2024-02-23T04:31:23Z","timestamp":1708662683000},"page":"299","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Neuropancreatology: The Nervous System and Pain Management in Pancreatic Diseases"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0658-4310","authenticated-orcid":false,"given":"Alberto","family":"Nicoletti","sequence":"first","affiliation":[{"name":"Pancreas Unit, CEMAD Centro Malattie dell\u2019Apparato Digerente, Medicina Interna e Gastroenterologia, Dipartimento di Medicina e Chirurgia Traslazionale, Universit\u00e0 Cattolica del Sacro Cuore, Fondazione Policlinico Universitario \u201cA. Gemelli\u201d IRCCS, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Federica","family":"Vitale","sequence":"additional","affiliation":[{"name":"Pancreas Unit, CEMAD Centro Malattie dell\u2019Apparato Digerente, Medicina Interna e Gastroenterologia, Dipartimento di Medicina e Chirurgia Traslazionale, Universit\u00e0 Cattolica del Sacro Cuore, Fondazione Policlinico Universitario \u201cA. Gemelli\u201d IRCCS, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7546-8041","authenticated-orcid":false,"given":"Mattia","family":"Paratore","sequence":"additional","affiliation":[{"name":"Pancreas Unit, CEMAD Centro Malattie dell\u2019Apparato Digerente, Medicina Interna e Gastroenterologia, Dipartimento di Medicina e Chirurgia Traslazionale, Universit\u00e0 Cattolica del Sacro Cuore, Fondazione Policlinico Universitario \u201cA. Gemelli\u201d IRCCS, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppe","family":"Quero","sequence":"additional","affiliation":[{"name":"Centro Pancreas, Chirurgia Digestiva, Dipartimento di Medicina e Chirurgia Traslazionale, Universit\u00e0 Cattolica del Sacro Cuore, Fondazione Policlinico Universitario \u201cA. Gemelli\u201d IRCCS, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7734-0538","authenticated-orcid":false,"given":"Marcantonio","family":"Negri","sequence":"additional","affiliation":[{"name":"Pancreas Unit, CEMAD Centro Malattie dell\u2019Apparato Digerente, Medicina Interna e Gastroenterologia, Dipartimento di Medicina e Chirurgia Traslazionale, Universit\u00e0 Cattolica del Sacro Cuore, Fondazione Policlinico Universitario \u201cA. Gemelli\u201d IRCCS, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Enrico Celestino","family":"Nista","sequence":"additional","affiliation":[{"name":"Pancreas Unit, CEMAD Centro Malattie dell\u2019Apparato Digerente, Medicina Interna e Gastroenterologia, Dipartimento di Medicina e Chirurgia Traslazionale, Universit\u00e0 Cattolica del Sacro Cuore, Fondazione Policlinico Universitario \u201cA. Gemelli\u201d IRCCS, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sergio","family":"Alfieri","sequence":"additional","affiliation":[{"name":"Centro Pancreas, Chirurgia Digestiva, Dipartimento di Medicina e Chirurgia Traslazionale, Universit\u00e0 Cattolica del Sacro Cuore, Fondazione Policlinico Universitario \u201cA. Gemelli\u201d IRCCS, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6230-1779","authenticated-orcid":false,"given":"Antonio","family":"Gasbarrini","sequence":"additional","affiliation":[{"name":"Pancreas Unit, CEMAD Centro Malattie dell\u2019Apparato Digerente, Medicina Interna e Gastroenterologia, Dipartimento di Medicina e Chirurgia Traslazionale, Universit\u00e0 Cattolica del Sacro Cuore, Fondazione Policlinico Universitario \u201cA. Gemelli\u201d IRCCS, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lorenzo","family":"Zileri Dal Verme","sequence":"additional","affiliation":[{"name":"Pancreas Unit, CEMAD Centro Malattie dell\u2019Apparato Digerente, Medicina Interna e Gastroenterologia, Dipartimento di Medicina e Chirurgia Traslazionale, Universit\u00e0 Cattolica del Sacro Cuore, Fondazione Policlinico Universitario \u201cA. Gemelli\u201d IRCCS, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,2,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1053\/j.gastro.2021.09.043","article-title":"Global Incidence of Acute Pancreatitis Is Increasing Over Time: A Systematic Review and Meta-Analysis","volume":"162","author":"Iannuzzi","year":"2022","journal-title":"Gastroenterology"},{"key":"ref_2","unstructured":"GBD2017 Pancreatic Cancer Collaborators (2019). The global, regional, and national burden of pancreatic cancer and its attributable risk factors in 195 countries and territories, 1990\u20132017: A systematic analysis for the Global Burden of Disease Study 2017. Lancet Gastroenterol. Hepatol., 4, 934\u2013947."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"744","DOI":"10.1053\/j.gastro.2020.10.007","article-title":"Worldwide Burden of, Risk Factors for, and Trends in Pancreatic Cancer","volume":"160","author":"Huang","year":"2021","journal-title":"Gastroenterology"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"21","DOI":"10.3389\/fnins.2019.00021","article-title":"Intrapancreatic Ganglia and Neural Regulation of Pancreatic Endocrine Secretion","volume":"13","author":"Li","year":"2019","journal-title":"Front. Neurosci."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"745","DOI":"10.1016\/j.beem.2014.05.002","article-title":"Neural control of the endocrine pancreas","volume":"28","author":"Caicedo","year":"2014","journal-title":"Best Pract. Res. Clin. Endocrinol. Metab."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/j.autneu.2006.10.001","article-title":"Autonomic pathways regulating pancreatic exocrine secretion","volume":"133","author":"Love","year":"2007","journal-title":"Auton. Neurosci."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"663022","DOI":"10.3389\/fendo.2021.663022","article-title":"Optical Imaging of Pancreatic Innervation","volume":"12","author":"Makhmutova","year":"2021","journal-title":"Front. Endocrinol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1097\/MOG.0b013e3283639326","article-title":"Modulation of pancreatic exocrine and endocrine secretion","volume":"29","author":"Chandra","year":"2013","journal-title":"Curr. Opin. Gastroenterol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/j.bpg.2007.10.016","article-title":"Pancreatic pain","volume":"22","author":"Ceyhan","year":"2008","journal-title":"Best Pract. Res. Clin. Gastroenterol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"726","DOI":"10.1016\/S0140-6736(20)31310-6","article-title":"Acute pancreatitis","volume":"396","author":"Boxhoorn","year":"2020","journal-title":"Lancet"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"382","DOI":"10.1001\/jama.2020.20317","article-title":"Acute Pancreatitis: A Review","volume":"325","author":"Mederos","year":"2021","journal-title":"JAMA"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"695","DOI":"10.1038\/nrc3131","article-title":"Perineural invasion and associated pain in pancreatic cancer","volume":"11","author":"Bapat","year":"2011","journal-title":"Nat. Rev. Cancer"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"2563","DOI":"10.1002\/1097-0142(19871115)60:10<2563::AID-CNCR2820601036>3.0.CO;2-L","article-title":"The prevalence of pain in four cancers","volume":"60","author":"Greenwald","year":"1987","journal-title":"Cancer"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"360","DOI":"10.1016\/0885-3924(91)90027-2","article-title":"Symptoms of pancreatic cancer","volume":"6","author":"Krech","year":"1991","journal-title":"J. Pain Symptom Manag."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Caban, M., and Ma\u0142ecka-Wojciesko, E. (2023). Gaps and Opportunities in the Diagnosis and Treatment of Pancreatic Cancer. Cancers, 15.","DOI":"10.3390\/cancers15235577"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1781","DOI":"10.1016\/j.cgh.2022.09.026","article-title":"Association of Chronic Pancreatitis Pain Features With Physical, Mental, and Social Health","volume":"21","author":"Yadav","year":"2022","journal-title":"Clin. Gastroenterol. Hepatol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1511","DOI":"10.1016\/j.pan.2020.08.017","article-title":"The quality of pain management in pancreatic cancer: A prospective multi-center study","volume":"20","author":"Damm","year":"2020","journal-title":"Pancreatology"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"782151","DOI":"10.3389\/fmed.2021.782151","article-title":"Pain Management in Acute Pancreatitis: A Systematic Review and Meta-Analysis of Randomised Controlled Trials","volume":"8","author":"Cai","year":"2021","journal-title":"Front. Med."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"460","DOI":"10.4253\/wjge.v13.i10.460","article-title":"Endoscopic ultrasonography-guided celiac plexus neurolysis in patients with unresectable pancreatic cancer: An update","volume":"13","author":"Valenciano","year":"2021","journal-title":"World J. Gastrointest. Endosc."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"720","DOI":"10.1016\/j.pan.2017.07.006","article-title":"Guidelines for the understanding and management of pain in chronic pancreatitis","volume":"17","author":"Drewes","year":"2017","journal-title":"Pancreatology"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"691777","DOI":"10.3389\/fnana.2021.691777","article-title":"Pancreas-Brain Crosstalk","volume":"15","author":"Lkhagvasuren","year":"2021","journal-title":"Front. Neuroanat."},{"key":"ref_22","first-page":"G780","article-title":"Neurons in the dorsal motor nucleus of the vagus may integrate vagal and spinal information from the GI tract","volume":"268","author":"Renehan","year":"1995","journal-title":"Am. J. Physiol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1417","DOI":"10.1016\/j.neuroscience.2005.10.055","article-title":"A quantitative analysis of the sensory and sympathetic innervation of the mouse pancreas","volume":"137","author":"Lindsay","year":"2006","journal-title":"Neuroscience"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1016\/j.pan.2012.02.010","article-title":"Pancreatic nociception\u2014Revisiting the physiology and pathophysiology","volume":"12","author":"Barreto","year":"2012","journal-title":"Pancreatology"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"G938","DOI":"10.1152\/ajpgi.00105.2002","article-title":"Primary sensory neurons: A common final pathway for inflammation in experimental pancreatitis in rats","volume":"283","author":"Nathan","year":"2002","journal-title":"Am. J. Physiol.-Gastrointest. Liver Physiol."},{"key":"ref_26","first-page":"389","article-title":"Substance P and calcitonin gene related peptide mediate pain in chronic pancreatitis and their expression is driven by nerve growth factor","volume":"12","author":"Liu","year":"2011","journal-title":"JOP"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"e14479","DOI":"10.14814\/phy2.14479","article-title":"Differential effects of vagus nerve stimulation strategies on glycemia and pancreatic secretions","volume":"8","author":"Payne","year":"2020","journal-title":"Physiol. Rep."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1679\/aohc.64.281","article-title":"Locations and innervation of cell bodies of sympathetic neurons projecting to the gastrointestinal tract in the rat","volume":"64","author":"Quinson","year":"2001","journal-title":"Arch. Histol. Cytol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/S0006-8993(97)00532-5","article-title":"CNS sites involved in sympathetic and parasympathetic control of the pancreas: A viral tracing study","volume":"766","author":"Jansen","year":"1997","journal-title":"Brain Res."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1016\/j.celrep.2013.06.019","article-title":"Sympathetic innervation during development is necessary for pancreatic islet architecture and functional maturation","volume":"4","author":"Borden","year":"2013","journal-title":"Cell Rep."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"823","DOI":"10.2337\/db16-1351","article-title":"Evidence That the Sympathetic Nervous System Elicits Rapid, Coordinated, and Reciprocal Adjustments of Insulin Secretion and Insulin Sensitivity During Cold Exposure","volume":"66","author":"Morton","year":"2017","journal-title":"Diabetes"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/j.cmet.2011.05.008","article-title":"Innervation patterns of autonomic axons in the human endocrine pancreas","volume":"14","author":"Abdulreda","year":"2011","journal-title":"Cell Metab."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"2714","DOI":"10.2337\/db13-1371","article-title":"Control of insulin secretion by cholinergic signaling in the human pancreatic islet","volume":"63","author":"Molina","year":"2014","journal-title":"Diabetes"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"756","DOI":"10.1002\/jcp.25176","article-title":"Neurotransmitters and Neuropeptides: New Players in the Control of Islet of Langerhans\u2019 Cell Mass and Function","volume":"231","author":"Moretti","year":"2016","journal-title":"J. Cell Physiol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"644","DOI":"10.1002\/cne.22541","article-title":"Vagal afferent innervation of the proximal gastrointestinal tract mucosa: Chemoreceptor and mechanoreceptor architecture","volume":"519","author":"Powley","year":"2011","journal-title":"J. Comp. Neurol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1626","DOI":"10.1523\/JNEUROSCI.10-05-01626.1990","article-title":"Innervation of the pancreas by neurons in the gut","volume":"10","author":"Kirchgessner","year":"1990","journal-title":"J. Neurosci."},{"key":"ref_37","first-page":"G339","article-title":"Presynaptic inhibition by serotonin of nerve-mediated secretion of pancreatic amylase","volume":"268","author":"Kirchgessner","year":"1995","journal-title":"Am. J. Physiol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1007\/s00125-017-4409-x","article-title":"Human pancreatic neuro-insular network in health and fatty infiltration","volume":"61","author":"Tang","year":"2018","journal-title":"Diabetologia"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"567","DOI":"10.1016\/j.tice.2016.10.005","article-title":"Structure of neuro-endocrine and neuro-epithelial interactions in human foetal pancreas","volume":"48","author":"Krivova","year":"2016","journal-title":"Tissue Cell"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1097\/00006676-200410000-00007","article-title":"Catecholamines and 5-hydroxytryptamine in tissues of the rabbit exocrine pancreas","volume":"29","author":"Yi","year":"2004","journal-title":"Pancreas"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"649","DOI":"10.1038\/nrgastro.2015.166","article-title":"Neural plasticity in pancreatitis and pancreatic cancer","volume":"12","author":"Demir","year":"2015","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1053\/j.gastro.2008.09.029","article-title":"Pancreatic neuropathy and neuropathic pain--a comprehensive pathomorphological study of 546 cases","volume":"136","author":"Ceyhan","year":"2009","journal-title":"Gastroenterology"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"97","DOI":"10.3389\/fphys.2012.00097","article-title":"Nerve-cancer interactions in the stromal biology of pancreatic cancer","volume":"3","author":"Demir","year":"2012","journal-title":"Front. Physiol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"8578","DOI":"10.1523\/JNEUROSCI.2185-06.2006","article-title":"Artemin overexpression in skin enhances expression of TRPV1 and TRPA1 in cutaneous sensory neurons and leads to behavioral sensitivity to heat and cold","volume":"26","author":"Elitt","year":"2006","journal-title":"J. Neurosci."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1093\/carcin\/bgt312","article-title":"The neurotrophic factor neurturin contributes toward an aggressive cancer cell phenotype, neuropathic pain and neuronal plasticity in pancreatic cancer","volume":"35","author":"Wang","year":"2014","journal-title":"Carcinogenesis"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"534","DOI":"10.1136\/gut.2006.105528","article-title":"The neurotrophic factor artemin influences the extent of neural damage and growth in chronic pancreatitis","volume":"56","author":"Ceyhan","year":"2007","journal-title":"Gut"},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Demir, I.E., Schorn, S., Schremmer-Danninger, E., Wang, K., Kehl, T., Giese, N.A., Alg\u00fcl, H., Friess, H., and Ceyhan, G.O. (2013). Perineural mast cells are specifically enriched in pancreatic neuritis and neuropathic pain in pancreatic cancer and chronic pancreatitis. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0060529"},{"key":"ref_48","first-page":"213","article-title":"Mast Cell-Nerve Interactions","volume":"15","author":"Bauer","year":"2000","journal-title":"News Physiol. Sci."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"2975","DOI":"10.1073\/pnas.84.9.2975","article-title":"Intestinal mucosal mast cells in normal and nematode-infected rat intestines are in intimate contact with peptidergic nerves","volume":"84","author":"Stead","year":"1987","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"693","DOI":"10.1053\/j.gastro.2003.11.055","article-title":"Activated mast cells in proximity to colonic nerves correlate with abdominal pain in irritable bowel syndrome","volume":"126","author":"Barbara","year":"2004","journal-title":"Gastroenterology"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1136\/gut.47.3.423","article-title":"Expression of interleukin 8 (IL-8) and substance P in human chronic pancreatitis","volume":"47","author":"Baccante","year":"2000","journal-title":"Gut"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"724","DOI":"10.1016\/j.cgh.2010.03.005","article-title":"Descending inhibitory pain modulation is impaired in patients with chronic pancreatitis","volume":"8","author":"Olesen","year":"2010","journal-title":"Clin. Gastroenterol. Hepatol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"418","DOI":"10.1097\/MEG.0b013e3283457b09","article-title":"Slowed EEG rhythmicity in patients with chronic pancreatitis: Evidence of abnormal cerebral pain processing?","volume":"23","author":"Olesen","year":"2011","journal-title":"Eur. J. Gastroenterol. Hepatol."},{"key":"ref_54","first-page":"815","article-title":"Altered resting state EEG in chronic pancreatitis patients: Toward a marker for chronic pain","volume":"6","author":"Jongsma","year":"2013","journal-title":"J. Pain Res."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1002\/j.1532-2149.2012.00155.x","article-title":"Cerebral excitability is abnormal in patients with painful chronic pancreatitis","volume":"17","author":"Olesen","year":"2013","journal-title":"Eur. J. Pain"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"742","DOI":"10.1159\/000321644","article-title":"Pain-associated adaptive cortical reorganisation in chronic pancreatitis","volume":"10","author":"Olesen","year":"2010","journal-title":"Pancreatology"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"968","DOI":"10.1002\/j.1532-2149.2013.00442.x","article-title":"Functional reorganization of brain networks in patients with painful chronic pancreatitis","volume":"18","author":"Lelic","year":"2014","journal-title":"Eur. J. Pain"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1554","DOI":"10.1136\/gut.2010.236620","article-title":"Altered brain microstructure assessed by diffusion tensor imaging in patients with chronic pancreatitis","volume":"60","author":"Frokjaer","year":"2011","journal-title":"Gut"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"434","DOI":"10.1016\/j.cgh.2011.11.024","article-title":"Reduced cortical thickness of brain areas involved in pain processing in patients with chronic pancreatitis","volume":"10","author":"Bouwense","year":"2012","journal-title":"Clin. Gastroenterol. Hepatol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1236361","DOI":"10.1126\/science.1236361","article-title":"Autonomic nerve development contributes to prostate cancer progression","volume":"341","author":"Magnon","year":"2013","journal-title":"Science"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"250ra115","DOI":"10.1126\/scitranslmed.3009569","article-title":"Denervation suppresses gastric tumorigenesis","volume":"6","author":"Zhao","year":"2014","journal-title":"Sci. Transl. Med."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"322","DOI":"10.1097\/00006676-200305000-00002","article-title":"Neural invasion in the staging of pancreatic cancer","volume":"26","author":"Pour","year":"2003","journal-title":"Pancreas"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1513","DOI":"10.3390\/cancers2031513","article-title":"Neural invasion in pancreatic cancer: The past, present and future","volume":"2","author":"Demir","year":"2010","journal-title":"Cancers"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1016\/0016-5085(94)90080-9","article-title":"Interaction of pancreatic ductal carcinoma with nerves leads to nerve damage","volume":"107","author":"Bockman","year":"1994","journal-title":"Gastroenterology"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1633","DOI":"10.1023\/A:1010684916863","article-title":"Brain-derived neurotrophic factor (BDNF) is upregulated and associated with pain in chronic pancreatitis","volume":"46","author":"Zhu","year":"2001","journal-title":"Dig. Dis. Sci."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"2419","DOI":"10.1200\/JCO.1999.17.8.2419","article-title":"Nerve growth factor expression correlates with perineural invasion and pain in human pancreatic cancer","volume":"17","author":"Zhu","year":"1999","journal-title":"J. Clin. Oncol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1093\/jnci\/djp456","article-title":"Paracrine regulation of pancreatic cancer cell invasion by peripheral nerves","volume":"102","author":"Gil","year":"2010","journal-title":"J. Natl. Cancer Inst."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1038\/nrn812","article-title":"The GDNF family: Signalling, biological functions and therapeutic value","volume":"3","author":"Airaksinen","year":"2002","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"9060","DOI":"10.1158\/0008-5472.CAN-08-1810","article-title":"The chemokine receptor CX3CR1 is involved in the neural tropism and malignant behavior of pancreatic ductal adenocarcinoma","volume":"68","author":"Marchesi","year":"2008","journal-title":"Cancer Res"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"925","DOI":"10.1001\/archsurg.2012.1094","article-title":"Clinical outcome in relation to timing of surgery in chronic pancreatitis: A nomogram to predict pain relief","volume":"147","author":"Ali","year":"2012","journal-title":"Arch. Surg."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"S-908","DOI":"10.1016\/S0016-5085(15)33079-1","article-title":"Tu1492 characteristics and predictors of large duct chronic calcific pancreatitis: A cross sectional analysis from a tertiary referral center","volume":"148","author":"Moran","year":"2015","journal-title":"Gastroenterology"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"556","DOI":"10.1097\/00006676-198611000-00015","article-title":"Pancreatic tissue pressure and pain in chronic pancreatitis","volume":"1","author":"Borly","year":"1986","journal-title":"Pancreas"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"462","DOI":"10.3109\/00365529009095516","article-title":"Evaluation of pancreatic tissue fluid pressure and pain in chronic pancreatitis. A longitudinal study","volume":"25","author":"Borly","year":"1990","journal-title":"Scand. J. Gastroenterol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1055\/s-2003-40237","article-title":"A prospective, randomized trial comparing endoscopic and surgical therapy for chronic pancreatitis","volume":"35","author":"Zboril","year":"2003","journal-title":"Endoscopy"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1124\/pr.117.014399","article-title":"Etiology and Pharmacology of Neuropathic Pain","volume":"70","author":"Alles","year":"2018","journal-title":"Pharmacol. Rev."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1159\/000082180","article-title":"Neurogenic inflammation and pancreatitis","volume":"4","author":"Liddle","year":"2004","journal-title":"Pancreatology"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1159\/000087654","article-title":"Role of neurogenic inflammation in pancreatitis and pancreatic pain","volume":"14","author":"Westlund","year":"2005","journal-title":"Neurosignals"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1111\/j.1749-6632.1991.tb33116.x","article-title":"The tachykinin neuroimmune connection in inflammatory pain","volume":"632","author":"Weihe","year":"1991","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1016\/S0304-3959(00)00436-X","article-title":"NK-1 receptor gene expression is related to pain in chronic pancreatitis","volume":"91","author":"Shrikhande","year":"2001","journal-title":"Pain"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"786","DOI":"10.1097\/SLA.0b013e318070d56e","article-title":"Neurokinin-2 receptor levels correlate with intensity, frequency, and duration of pain in chronic pancreatitis","volume":"246","author":"Michalski","year":"2007","journal-title":"Ann. Surg."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"615","DOI":"10.1097\/00000658-199911000-00002","article-title":"Nerve growth factor and its high-affinity receptor in chronic pancreatitis","volume":"230","author":"Friess","year":"1999","journal-title":"Ann. Surg."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1038\/nrgastro.2011.274","article-title":"Unraveling the mystery of pain in chronic pancreatitis","volume":"9","author":"Pasricha","year":"2012","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1016\/j.pain.2008.12.011","article-title":"Basic and clinical aspects of gastrointestinal pain","volume":"141","author":"Knowles","year":"2009","journal-title":"Pain"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1159\/000108958","article-title":"Pain in chronic pancreatitis: A salutogenic mechanism or a maladaptive brain response?","volume":"7","author":"Fregni","year":"2007","journal-title":"Pancreatology"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1016\/S0002-9610(99)80089-0","article-title":"Pitfalls of distal pancreatectomy for relief of pain in chronic pancreatitis","volume":"171","author":"Rattner","year":"1996","journal-title":"Am. J. Surg."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1007\/s00795-007-0374-7","article-title":"Effects of sensory denervation by neonatal capsaicin administration on experimental pancreatitis induced by dibutyltin dichloride","volume":"40","author":"Ikeura","year":"2007","journal-title":"Med. Mol. Morphol."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"47","DOI":"10.3748\/wjg.v21.i1.47","article-title":"Systematic mechanism-orientated approach to chronic pancreatitis pain","volume":"21","author":"Bouwense","year":"2015","journal-title":"World J. Gastroenterol."},{"key":"ref_88","doi-asserted-by":"crossref","unstructured":"Wilder-Smith, O.H. (2013). A Paradigm-Shift in Pain Medicine, River Publishers.","DOI":"10.13052\/rp-9788793102545"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"v56","DOI":"10.1093\/annonc\/mdv295","article-title":"Cancer of the pancreas: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up","volume":"26","author":"Ducreux","year":"2015","journal-title":"Ann. Oncol."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"1870","DOI":"10.1001\/jama.1995.03530230056031","article-title":"The WHO analgesic ladder for cancer pain management. Stepping up the quality of its evaluation","volume":"274","author":"Jadad","year":"1995","journal-title":"JAMA"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"159","DOI":"10.2217\/pmt-2021-0012","article-title":"Pain management consultation for acute pancreatitis: Impact on length of stay and opioid utilization","volume":"12","author":"Ushe","year":"2022","journal-title":"Pain Manag."},{"key":"ref_92","doi-asserted-by":"crossref","unstructured":"Working Group IAP\/APA Acute Pancreatitis Guidelines (2013). IAP\/APA evidence-based guidelines for the management of acute pancreatitis. Pancreatology, 13, e1\u2013e15.","DOI":"10.1016\/j.pan.2013.07.063"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"612","DOI":"10.1016\/j.clnu.2020.01.004","article-title":"ESPEN guideline on clinical nutrition in acute and chronic pancreatitis","volume":"39","author":"Arvanitakis","year":"2020","journal-title":"Clin. Nutr."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"725","DOI":"10.1177\/2050640615612368","article-title":"Timing of oral refeeding in acute pancreatitis: A systematic review and meta-analysis","volume":"4","author":"Horibe","year":"2015","journal-title":"United Eur. Gastroenterol. J."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1097\/SLA.0000000000004596","article-title":"Immediate Oral Refeeding in Patients With Mild and Moderate Acute Pancreatitis: A Multicenter, Randomized Controlled Trial (PADI trial)","volume":"274","author":"Gordo","year":"2021","journal-title":"Ann. Surg."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"722","DOI":"10.1016\/j.clnu.2016.06.006","article-title":"Incidence and predictors of oral feeding intolerance in acute pancreatitis: A systematic review, meta-analysis, and meta-regression","volume":"36","author":"Bevan","year":"2017","journal-title":"Clin. Nutr."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1016\/j.cgh.2007.12.040","article-title":"Dietary counseling versus dietary supplements for malnutrition in chronic pancreatitis: A randomized controlled trial","volume":"6","author":"Singh","year":"2008","journal-title":"Clin. Gastroenterol. Hepatol."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1177\/2050640616684695","article-title":"United European Gastroenterology evidence-based guidelines for the diagnosis and therapy of chronic pancreatitis (HaPanEU)","volume":"5","author":"Rosendahl","year":"2017","journal-title":"United Eur. Gastroenterol. J."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"2898","DOI":"10.1016\/j.clnu.2021.02.005","article-title":"ESPEN practical guideline: Clinical Nutrition in cancer","volume":"40","author":"Muscaritoli","year":"2021","journal-title":"Clin. Nutr."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"1996","DOI":"10.1016\/j.ebiom.2015.11.023","article-title":"Alcohol Consumption as a Risk Factor for Acute and Chronic Pancreatitis: A Systematic Review and a Series of Meta-analyses","volume":"2","author":"Samokhvalov","year":"2015","journal-title":"EBioMedicine"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"1201","DOI":"10.1097\/MPA.0000000000000176","article-title":"Smoking and risk for acute pancreatitis: A systematic review and meta-analysis","volume":"43","author":"Yuhara","year":"2014","journal-title":"Pancreas"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1159\/000332196","article-title":"The emerging role of smoking in the development of pancreatitis","volume":"11","author":"Alexandre","year":"2011","journal-title":"Pancreatology"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1093\/alcalc\/agt019","article-title":"Abstinence after first acute alcohol-associated pancreatitis protects against recurrent pancreatitis and minimizes the risk of pancreatic dysfunction","volume":"48","author":"Nikkola","year":"2013","journal-title":"Alcohol Alcohol."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"34","DOI":"10.4236\/jct.2013.410A005","article-title":"Smoking and Pancreatic Disease","volume":"4","author":"Edderkaoui","year":"2013","journal-title":"J. Cancer Ther."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"1115","DOI":"10.1177\/2050640620938987","article-title":"Pancreatic exocrine insufficiency and pancreatic enzyme replacement therapy in patients with advanced pancreatic cancer: A systematic review and meta-analysis","volume":"8","author":"Avci","year":"2020","journal-title":"United Eur. Gastroenterol. J."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"878","DOI":"10.1007\/s00268-021-06420-w","article-title":"Analgesia in the Initial Management of Acute Pancreatitis: A Systematic Review and Meta-Analysis of Randomised Controlled Trials","volume":"46","author":"Thavanesan","year":"2022","journal-title":"World J. Surg."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"492","DOI":"10.1111\/j.1533-2500.2011.00474.x","article-title":"26. Pain in chronic pancreatitis","volume":"11","author":"Puylaert","year":"2011","journal-title":"Pain Pract."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1186\/s13017-019-0247-0","article-title":"2019 WSES guidelines for the management of severe acute pancreatitis","volume":"14","author":"Tolonen","year":"2019","journal-title":"World J. Emerg. Surg."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1146\/annurev-med-062613-093100","article-title":"Opioid Receptors","volume":"67","author":"Stein","year":"2016","journal-title":"Annu. Rev. Med."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"860","DOI":"10.1124\/pr.110.003145","article-title":"Modulation of peripheral sensory neurons by the immune system: Implications for pain therapy","volume":"63","author":"Stein","year":"2011","journal-title":"Pharmacol. Rev."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1016\/S0016-5107(94)70027-3","article-title":"Opioids and the sphincter of Oddi","volume":"40","author":"Sherman","year":"1994","journal-title":"Gastrointest. Endosc."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"1266","DOI":"10.1111\/j.1572-0241.2001.03536.x","article-title":"Narcotic analgesic effects on the sphincter of Oddi: A review of the data and therapeutic implications in treating pancreatitis","volume":"96","author":"Thompson","year":"2001","journal-title":"Am. J. Gastroenterol."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"532","DOI":"10.1016\/j.cgh.2023.10.021","article-title":"Buprenorphine Versus Diclofenac for Pain Relief in Acute Pancreatitis: A Double-Blinded Randomized Controlled Trial","volume":"22","author":"Saini","year":"2024","journal-title":"Clin. Gastroenterol. Hepatol."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1002\/ejp.970","article-title":"European Pain Federation position paper on appropriate opioid use in chronic pain management","volume":"21","author":"Christrup","year":"2017","journal-title":"Eur. J. Pain"},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1016\/j.sjpain.2015.12.005","article-title":"Definition, diagnosis and treatment strategies for opioid-induced bowel dysfunction\u2013Recommendations of the Nordic Working Group","volume":"11","author":"Drewes","year":"2016","journal-title":"Scand. J. Pain"},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1038\/ajgsup.2014.6","article-title":"The narcotic bowel syndrome: A recent update","volume":"2","author":"Drossman","year":"2014","journal-title":"Am. J. Gastroenterol. Suppl."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"879","DOI":"10.2165\/00003088-200443130-00004","article-title":"Clinical pharmacology of tramadol","volume":"43","author":"Grond","year":"2004","journal-title":"Clin. Pharmacokinet."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"1107","DOI":"10.1023\/A:1026607703352","article-title":"Effect of tramadol and morphine on pain and gastrointestinal motor function in patients with chronic pancreatitis","volume":"44","author":"Hill","year":"1999","journal-title":"Dig. Dis. Sci."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"43","DOI":"10.3390\/cancers3010043","article-title":"Pain management in pancreatic cancer","volume":"3","author":"Hameed","year":"2010","journal-title":"Cancers"},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"e659","DOI":"10.1200\/OP.21.00488","article-title":"Opioid Prescription Is Associated With Increased Survival in Older Adult Patients With Pancreatic Cancer in the United States: A Propensity Score Analysis","volume":"18","author":"Zylberberg","year":"2022","journal-title":"JCO Oncol. Pract."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"829","DOI":"10.1111\/j.1526-4637.2009.00653.x","article-title":"Do opioids induce hyperalgesia in humans? An evidence-based structured review","volume":"10","author":"Fishbain","year":"2009","journal-title":"Pain Med."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"385","DOI":"10.5055\/jom.2010.0036","article-title":"Defining clinical issues around tolerance, hyperalgesia, and addiction: A quantitative and qualitative outcome study of long-term opioid dosing in a chronic pain practice","volume":"6","author":"Schneider","year":"2010","journal-title":"J. Opioid Manag."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"598","DOI":"10.1016\/j.pain.2012.12.026","article-title":"Opioid withdrawal increases transient receptor potential vanilloid 1 activity in a protein kinase A-dependent manner","volume":"154","author":"Spahn","year":"2013","journal-title":"Pain"},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"536","DOI":"10.1053\/j.gastro.2011.04.003","article-title":"Pregabalin reduces pain in patients with chronic pancreatitis in a randomized, controlled trial","volume":"141","author":"Olesen","year":"2011","journal-title":"Gastroenterology"},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1016\/j.brainres.2010.04.035","article-title":"Analgesic effects of gabapentin on mechanical hypersensitivity in a rat model of chronic pancreatitis","volume":"1337","author":"Liao","year":"2010","journal-title":"Brain Res."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"673","DOI":"10.1097\/MPA.0b013e318215ad38","article-title":"Effects of systemic administration of a local anesthetic on pain in acute pancreatitis: A randomized clinical trial","volume":"40","author":"Layer","year":"2011","journal-title":"Pancreas"},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"2290","DOI":"10.1055\/s-0030-1267512","article-title":"Procaine infusion for pain treatment of acute pancreatitis: A randomized, placebo-controlled double-blind trial","volume":"135","author":"Wilms","year":"2010","journal-title":"Dtsch. Med. Wochenschr."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"1319","DOI":"10.1080\/003655200453692","article-title":"Buprenorphine or procaine for pain relief in acute pancreatitis. A prospective randomized study","volume":"35","author":"Jakobs","year":"2000","journal-title":"Scand. J. Gastroenterol."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1159\/000076541","article-title":"Procaine hydrochloride fails to relieve pain in patients with acute pancreatitis","volume":"69","author":"Kahl","year":"2004","journal-title":"Digestion"},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1016\/S1474-4422(14)70251-0","article-title":"Pharmacotherapy for neuropathic pain in adults: A systematic review and meta-analysis","volume":"14","author":"Finnerup","year":"2015","journal-title":"Lancet Neurol."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"35448","DOI":"10.18632\/oncotarget.26234","article-title":"Naturally occurring compounds as pancreatic cancer therapeutics","volume":"9","author":"Lohse","year":"2018","journal-title":"Oncotarget"},{"key":"ref_132","doi-asserted-by":"crossref","unstructured":"Kapral, M., Wawszczyk, J., Jesse, K., Paul-Samojedny, M., Ku\u015bmierz, D., and W\u0119glarz, L. (2017). Inositol Hexaphosphate Inhibits Proliferation and Induces Apoptosis of Colon Cancer Cells by Suppressing the AKT\/mTOR Signaling Pathway. Molecules, 22.","DOI":"10.3390\/molecules22101657"},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"8","DOI":"10.3747\/co.23.3099","article-title":"Integrating cannabis into clinical cancer care","volume":"23","author":"Abrams","year":"2016","journal-title":"Curr. Oncol."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"12448","DOI":"10.3748\/wjg.v21.i43.12448","article-title":"Epidural anesthesia improves pancreatic perfusion and decreases the severity of acute pancreatitis","volume":"21","author":"Sadowski","year":"2015","journal-title":"World J. Gastroenterol."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"e198","DOI":"10.1097\/CCM.0000000000002874","article-title":"Thoracic Epidural Analgesia and Mortality in Acute Pancreatitis: A Multicenter Propensity Analysis","volume":"46","author":"Jabaudon","year":"2018","journal-title":"Crit. Care Med."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1186\/s13054-023-04502-w","article-title":"Thoracic epidural analgesia in intensive care unit patients with acute pancreatitis: The EPIPAN multicenter randomized controlled trial","volume":"27","author":"Jabaudon","year":"2023","journal-title":"Crit. Care"},{"key":"ref_137","first-page":"CD007519","article-title":"Celiac plexus block for pancreatic cancer pain in adults","volume":"2019","author":"Arcidiacono","year":"2011","journal-title":"Cochrane. Database. Syst. Rev."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"652","DOI":"10.1111\/papr.13143","article-title":"Systematic review and meta-analysis of celiac plexus neurolysis for abdominal pain associated with unresectable pancreatic cancer","volume":"22","author":"Okita","year":"2022","journal-title":"Pain Pract."},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"900","DOI":"10.1111\/j.1572-0241.1999.01042.x","article-title":"A Prospective Randomized Comparison of Endoscopic Ultrasound- and Computed Tomography-Guided Celiac Plexus Block for Managing Chronic Pancreatitis Pain","volume":"94","author":"Gress","year":"1999","journal-title":"Am. J. Gastroenterol."},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1111\/ner.13051","article-title":"Spinal Cord Stimulation for Management of Pain in Chronic Pancreatitis: A Systematic Review of Efficacy and Complications","volume":"23","author":"Ratnayake","year":"2020","journal-title":"Neuromodulation"},{"key":"ref_141","doi-asserted-by":"crossref","unstructured":"Ciapa\u0142a, K., and Mika, J. (2023). Advances in Neuropathic Pain Research: Selected Intracellular Factors as Potential Targets for Multidirectional Analgesics. Pharmaceuticals, 16.","DOI":"10.3390\/ph16111624"},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"1822","DOI":"10.1053\/j.gastro.2006.02.022","article-title":"The vagus nerve and nicotinic receptors modulate experimental pancreatitis severity in mice","volume":"130","author":"Giebelen","year":"2006","journal-title":"Gastroenterology"},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1097\/MPA.0b013e3182a85c21","article-title":"Pharmacological cholinergic stimulation as a therapeutic tool in experimental necrotizing pancreatitis","volume":"43","author":"Schneider","year":"2014","journal-title":"Pancreas"},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"2910","DOI":"10.3748\/wjg.v28.i25.2910","article-title":"Multiple roles for cholinergic signaling in pancreatic diseases","volume":"28","author":"Yang","year":"2022","journal-title":"World J. Gastroenterol."},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1016\/j.tips.2005.12.001","article-title":"Novel class of pain drugs based on antagonism of NGF","volume":"27","author":"Hefti","year":"2006","journal-title":"Trends Pharmacol. Sci."},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"349","DOI":"10.2165\/0063030-200822060-00002","article-title":"Targeting nerve growth factor in pain: What is the therapeutic potential?","volume":"22","author":"Watson","year":"2008","journal-title":"BioDrugs"},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"2985","DOI":"10.1073\/pnas.0611253104","article-title":"The function neutralizing anti-TrkA antibody MNAC13 reduces inflammatory and neuropathic pain","volume":"104","author":"Ugolini","year":"2007","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1016\/j.bone.2010.09.019","article-title":"Sustained blockade of neurotrophin receptors TrkA, TrkB and TrkC reduces non-malignant skeletal pain but not the maintenance of sensory and sympathetic nerve fibers","volume":"48","author":"Ghilardi","year":"2011","journal-title":"Bone"},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"5152","DOI":"10.1021\/jm9006559","article-title":"Identification of N,1,4,4-tetramethyl-8-{[4-(4-methylpiperazin-1-yl)phenyl]amino}-4,5-dihydro-1H-pyrazolo[4,3-h]quinazoline-3-carboxamide (PHA-848125), a potent, orally available cyclin dependent kinase inhibitor","volume":"52","author":"Brasca","year":"2009","journal-title":"J. Med. Chem."},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1136\/gut.2005.073205","article-title":"Vanilloids in pancreatic cancer: Potential for chemotherapy and pain management","volume":"55","author":"Hartel","year":"2006","journal-title":"Gut"},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1097\/CAD.0b013e32832bd1e3","article-title":"Prevention of pancreatic cancer by the beta-blocker propranolol","volume":"20","author":"Schuller","year":"2009","journal-title":"Anti-Cancer Drugs"},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"19","DOI":"10.4161\/cbt.10.1.11944","article-title":"\u03b22-adrenergic antagonists suppress pancreatic cancer cell invasion by inhibiting CREB, NF-\u03baB and AP-1","volume":"10","author":"Zhang","year":"2010","journal-title":"Cancer Biol. Ther."},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"991","DOI":"10.1111\/bph.12366","article-title":"HDAC inhibitors restore C-fibre sensitivity in experimental neuropathic pain model","volume":"170","author":"Matsushita","year":"2013","journal-title":"Br. J. Pharmacol."},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"1789","DOI":"10.21873\/anticanres.14133","article-title":"Pathogenesis and Treatment of Pancreatic Cancer Related Pain","volume":"40","author":"Lohse","year":"2020","journal-title":"Anticancer Res."},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"1298","DOI":"10.1097\/MPA.0000000000001912","article-title":"Rationale for and Development of the Pancreatic Quantitative Sensory Testing Consortium to Study Pain in Chronic Pancreatitis","volume":"50","author":"Phillips","year":"2021","journal-title":"Pancreas"}],"container-title":["Life"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-1729\/14\/3\/299\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T14:03:31Z","timestamp":1760105011000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-1729\/14\/3\/299"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,2,23]]},"references-count":155,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2024,3]]}},"alternative-id":["life14030299"],"URL":"https:\/\/doi.org\/10.3390\/life14030299","relation":{},"ISSN":["2075-1729"],"issn-type":[{"value":"2075-1729","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,2,23]]}}}