Neurogenic inflammation and pain in acute pancreatitis_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

WU Yongzi ¹ , HAN Chenxia ¹ , CAI Wenhao ^1,2 , LIU Tingting ¹ ,  HUANG Wei ^1,3,4

1. West China Centre of Excellence for Pancreatitis, Institute of Integrated Traditional Chinese and Western Medicine, West China Hospital, Sichuan University, Chengdu 610041, P. R. China;
2. Liverpool Pancreatitis Research Group, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool L69 3GE, United Kingdom;
3. West China Biobanks, West China Hospital, Sichuan University, Chengdu 610041, P. R. China;
4. Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu 610041, P. R. China;

Corresponding author：

HUANG Wei, Email: dr_wei_huang@scu.edu.cn

Keywords：

acute pancreatitis; pain; neurogenic inflammation

DOI：

10.7507/1007-9424.202207076

Video：

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Acute pancreatitis (AP) is an acute abdominal disease characterised by inflammation of the pancreas. Acute severe upper abdominal pain is the leading symptom and primary reason for emergence hospital admission of AP patients. Nowadays, more and more research has focused on the cross-talk between the exocrine pancreas and pancreatic projecting neurons (neurogenic inflammation) for pain in AP. Elucidating the molecular mechanisms of neurogenic inflammation for pain in AP will provide insights into targeted analgesics development in this setting.

Citation： WU Yongzi, HAN Chenxia, CAI Wenhao, LIU Tingting, HUANG Wei. Neurogenic inflammation and pain in acute pancreatitis. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2022, 29(9): 1165-1168. doi: 10.7507/1007-9424.202207076 Copy

1.	Mederos MA, Reber HA, Girgis MD. Acute pancreatitis: a review. JAMA, 2021, 325(4): 382-390.
2.	Banks PA, Bollen TL, Dervenis C, et al. Classification of acute pancreatitis—2012: revision of the Atlanta classification and definitions by international consensus. Gut, 2013, 62(1): 102-111.
3.	Phillip V, Schuster T, Hagemes F, et al. Time period from onset of pain to hospital admission and patients' awareness in acute pancreatitis. Pancreas, 2013, 42(4): 647-654.
4.	Buxbaum J, Quezada M, Chong B, et al. The pancreatitis activity scoring system predicts clinical outcomes in acute pancreatitis: findings from a prospective cohort study. Am J Gastroenterol, 2018, 113(5): 755-764.
5.	急性胰腺炎中西医结合诊疗指南. 中国中西医结合学会团体标. T/CAIM 007-202.
6.	Bindu S, Mazumder S, Bandyopadhyay U. Non-steroidal anti-inflammatory drugs (NSAIDs) and organ damage: A current perspective. Biochem Pharmacol, 2020, 180: 114147. doi: 10.1016/j.bcp.2020.114147.
7.	Yekkirala AS, Roberson DP, Bean BP, et al. Breaking barriers to novel analgesic drug development. Nature reviews Drug discovery, 2017, 16(8): 545-564.
8.	Thavanesan N, White S, Lee S, et al. Analgesia in the initial management of acute pancreatitis: a systematic review and meta-analysis of randomised controlled trials. World J Surg, 2022, 46(4): 878-890.
9.	Cai W, Liu F, Wen Y, et al. Pain management in acute pancreatitis: a systematic review and meta-analysis of randomised controlled trials. Front Med (Lausanne), 2021, 8: 782151. doi: 10.3389/fmed.2021.782151.
10.	Drewes AM, Olesen AE, Farmer AD, et al. Gastrointestinal pain. Nat Rev Dis Primers, 2020, 6(1): 1. doi: 10.1038/s41572-019-0135-7.
11.	Lindsay TH, Halvorson KG, Peters CM, et al. A quantitative analysis of the sensory and sympathetic innervation of the mouse pancreas. Neuroscience, 2006, 137(4): 1417-1426.
12.	DiMagno EP. Toward understanding (and management) of painful chronic pancreatitis. Gastroenterology, 1999, 116(5): 1252-1257.
13.	Choi JE, Di Nardo A. Skin neurogenic inflammation. Semin Immunopathol, 2018, 40(3): 249-259.
14.	Lasagni Vitar RM, Rama P, Ferrari G. The two-faced effects of nerves and neuropeptides in corneal diseases. Prog Retin Eye Res, 2022, 86: 100974. doi: 10.1016/j.preteyeres.2021. 100974.
15.	Vera-Portocarrero L, Westlund KN. Role of neurogenic inflammation in pancreatitis and pancreatic pain. Neurosignals, 2005, 14(4): 158-165.
16.	Schnipper J, Dhennin-Duthille I, Ahidouch A, et al. Ion channel signature in healthy pancreas and pancreatic ductal adenocarcinoma. Front Pharmacol, 2020, 11: 568993. doi: 10.3389/fphar.2020.568993.
17.	Wick EC, Hoge SG, Grahn SW, 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, 2006, 290(5): G959-G969.
18.	Ceppa E, Cattaruzza F, Lyo V, et al. Transient receptor potential ion channels V4 and A1 contribute to pancreatitis pain in mice. Am J Physiol Gastrointest Liver Physiol, 2010, 299(3): G556-G571.
19.	Grundy L, Erickson A, Brierley SM. Visceral pain. Annu Rev Physiol, 2019, 81: 261-284.
20.	Vigna SR, Shahid RA, Nathan JD, et al. Leukotriene B4 mediates inflammation via TRPV1 in duct obstruction-induced pancreatitis in rats. Pancreas, 2011, 40(5): 708-714.
21.	Nathan JD, Patel AA, McVey DC, et al. Capsaicin vanilloid receptor-1 mediates substance P release in experimental pancreatitis. Am J Physiol Gastrointest Liver Physiol, 2001, 281(5): G1322-G1328.
22.	Romac JM, McCall SJ, Humphrey JE, et al. Pharmacologic disruption of TRPV1-expressing primary sensory neurons but not genetic deletion of TRPV1 protects mice against pancreatitis. Pancreas, 2008, 36(4): 394-401.
23.	Schwartz ES, Christianson JA, Chen X, et al. Synergistic role of TRPV1 and TRPA1 in pancreatic pain and inflammation. Gastroenterology, 2011, 140(4): 1283-1291.
24.	Terada Y, Fujimura M, Nishimura S, et al. Contribution of TRPA1 as a downstream signal of proteinase-activated receptor-2 to pancreatic pain. J Pharmacol Sci, 2013, 123(3): 284-287.
25.	Kanju P, Chen Y, Lee W, et al. Small molecule dual-inhibitors of TRPV4 and TRPA1 for attenuation of inflammation and pain. Sci Rep, 2016, 6: 26894. doi: 10.1038/srep26894.
26.	Swain SM, Romac JM, Shahid RA, et al. TRPV4 channel opening mediates pressure-induced pancreatitis initiated by Piezo1 activation. J Clin Invest, 2020, 130(5): 2527-2541.
27.	Steinhoff MS, von Mentzer B, Geppetti P, et al. Tachykinins and their receptors: contributions to physiological control and the mechanisms of disease. Physiol Rev, 2014, 94(1): 265-301.
28.	Ramnath RD, Sun J, Bhatia M. Involvement of SRC family kinases in substance P-induced chemokine production in mouse pancreatic acinar cells and its significance in acute pancreatitis. J Pharmacol Exp Ther, 2009, 329(2): 418-428.
29.	Koh YH, Tamizhselvi R, Moochhala S, et al. Role of protein kinase C in caerulein induced expression of substance P and neurokinin-1-receptors in murine pancreatic acinar cells. J Cell Mol Med, 2011, 15(10): 2139-2149.
30.	Li B, Han X, Ye X, et al. Substance P-regulated leukotriene B4 production promotes acute pancreatitis-associated lung injury through neutrophil reverse migration. Int Immunopharmacol, 2018, 57: 147-156.
31.	Ramnath RD, Bhatia M. Substance P treatment stimulates chemokine synthesis in pancreatic acinar cells via the activation of NF-kappaB. Am J Physiol Gastrointest Liver Physiol, 2006, 291(6): G1113-G1119.
32.	Han C, Du D, Wen Y, et al. Chaiqin chengqi decoction ameliorates acute pancreatitis in mice via inhibition of neuron activation-mediated acinar cell SP/NK1R signaling pathways. J Ethnopharmacol, 2021, 274: 114029. doi: 10.1016/j.jep.2021.114029.
33.	Russell FA, King R, Smillie SJ, et al. Calcitonin gene-related peptide: physiology and pathophysiology. Physiol Rev, 2014, 94(4): 1099-1142.
34.	Sternini C, Brecha N. Immunocytochemical identification of islet cells and nerve fibers containing calcitonin gene-related peptide-like immunoreactivity in the rat pancreas. Gastroenterology, 1986, 90(5 Pt 1): 1155-1163.
35.	Warzecha Z, Dembiński A, Ceranowicz P, et al. The influence of sensory nerves and CGRP on the pancreatic regeneration after repeated episodes of acute pancreatitis in rats. J Physiol Pharmacol. 2000, 51(3): 449-461.
36.	Warzecha Z, Dembiński A, Ceranowicz P, et al. Protective effect of calcitonin gene-related peptide against caerulein-induced pancreatitis in rats. J Physiol Pharmacol. 1997, 48(4): 775-787.
37.	Warzecha Z, Dembiński A, Ceranowicz P, et al. Calcitonin gene-related peptide can attenuate or augment pancreatic damage in caerulein-induced pancreatitis in rats. J Physiol Pharmacol. 1999, 50(1): 49-62.
38.	Wick EC, Pikios S, Grady EF, et al. Calcitonin gene-related peptide partially mediates nociception in acute experimental pancreatitis. Surgery, 2006, 139(2): 197-201.
39.	Nishimura S, Fukushima O, Ishikura H, et al. Hydrogen sulfide as a novel mediator for pancreatic pain in rodents. Gut, 2009, 58(6): 762-770.
40.	Terada Y, Fujimura M, Nishimura S, et al. Roles of Cav3. 2 and TRPA1 channels targeted by hydrogen sulfide in pancreatic nociceptive processing in mice with or without acute pancreatitis. J Neurosci Res, 2015, 93(2): 361-369.
41.	Qiu Y, Huang L, Fu J, et al. TREK channel family activator with a well-defined structure-activation relationship for pain and neurogenic inflammation. J Med Chem, 2020, 63(7): 3665-3677.
42.	Li J, Liu Y, Yuan L, et al. A tissue-like neurotransmitter sensor for the brain and gut. Nature, 2022, 606(7912): 94-101.
43.	Zhang Q, Ren Y, Mo Y, et al. Inhibiting Hv1 channel in peripheral sensory neurons attenuates chronic inflammatory pain and opioid side effects. Cell Res, 2022, 32(5): 461-476.
44.	Beaulieu-Laroche L, Christin M, Donoghue A, et al. TACAN is an ion channel involved in sensing mechanical pain. Cell, 2020, 180(5): 956-967.

1. Mederos MA, Reber HA, Girgis MD. Acute pancreatitis: a review. JAMA, 2021, 325(4): 382-390.
2. Banks PA, Bollen TL, Dervenis C, et al. Classification of acute pancreatitis—2012: revision of the Atlanta classification and definitions by international consensus. Gut, 2013, 62(1): 102-111.
3. Phillip V, Schuster T, Hagemes F, et al. Time period from onset of pain to hospital admission and patients' awareness in acute pancreatitis. Pancreas, 2013, 42(4): 647-654.
4. Buxbaum J, Quezada M, Chong B, et al. The pancreatitis activity scoring system predicts clinical outcomes in acute pancreatitis: findings from a prospective cohort study. Am J Gastroenterol, 2018, 113(5): 755-764.
5. 急性胰腺炎中西医结合诊疗指南. 中国中西医结合学会团体标. T/CAIM 007-202.
6. Bindu S, Mazumder S, Bandyopadhyay U. Non-steroidal anti-inflammatory drugs (NSAIDs) and organ damage: A current perspective. Biochem Pharmacol, 2020, 180: 114147. doi: 10.1016/j.bcp.2020.114147.
7. Yekkirala AS, Roberson DP, Bean BP, et al. Breaking barriers to novel analgesic drug development. Nature reviews Drug discovery, 2017, 16(8): 545-564.
8. Thavanesan N, White S, Lee S, et al. Analgesia in the initial management of acute pancreatitis: a systematic review and meta-analysis of randomised controlled trials. World J Surg, 2022, 46(4): 878-890.
9. Cai W, Liu F, Wen Y, et al. Pain management in acute pancreatitis: a systematic review and meta-analysis of randomised controlled trials. Front Med (Lausanne), 2021, 8: 782151. doi: 10.3389/fmed.2021.782151.
10. Drewes AM, Olesen AE, Farmer AD, et al. Gastrointestinal pain. Nat Rev Dis Primers, 2020, 6(1): 1. doi: 10.1038/s41572-019-0135-7.
11. Lindsay TH, Halvorson KG, Peters CM, et al. A quantitative analysis of the sensory and sympathetic innervation of the mouse pancreas. Neuroscience, 2006, 137(4): 1417-1426.
12. DiMagno EP. Toward understanding (and management) of painful chronic pancreatitis. Gastroenterology, 1999, 116(5): 1252-1257.
13. Choi JE, Di Nardo A. Skin neurogenic inflammation. Semin Immunopathol, 2018, 40(3): 249-259.
14. Lasagni Vitar RM, Rama P, Ferrari G. The two-faced effects of nerves and neuropeptides in corneal diseases. Prog Retin Eye Res, 2022, 86: 100974. doi: 10.1016/j.preteyeres.2021. 100974.
15. Vera-Portocarrero L, Westlund KN. Role of neurogenic inflammation in pancreatitis and pancreatic pain. Neurosignals, 2005, 14(4): 158-165.
16. Schnipper J, Dhennin-Duthille I, Ahidouch A, et al. Ion channel signature in healthy pancreas and pancreatic ductal adenocarcinoma. Front Pharmacol, 2020, 11: 568993. doi: 10.3389/fphar.2020.568993.
17. Wick EC, Hoge SG, Grahn SW, 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, 2006, 290(5): G959-G969.
18. Ceppa E, Cattaruzza F, Lyo V, et al. Transient receptor potential ion channels V4 and A1 contribute to pancreatitis pain in mice. Am J Physiol Gastrointest Liver Physiol, 2010, 299(3): G556-G571.
19. Grundy L, Erickson A, Brierley SM. Visceral pain. Annu Rev Physiol, 2019, 81: 261-284.
20. Vigna SR, Shahid RA, Nathan JD, et al. Leukotriene B4 mediates inflammation via TRPV1 in duct obstruction-induced pancreatitis in rats. Pancreas, 2011, 40(5): 708-714.
21. Nathan JD, Patel AA, McVey DC, et al. Capsaicin vanilloid receptor-1 mediates substance P release in experimental pancreatitis. Am J Physiol Gastrointest Liver Physiol, 2001, 281(5): G1322-G1328.
22. Romac JM, McCall SJ, Humphrey JE, et al. Pharmacologic disruption of TRPV1-expressing primary sensory neurons but not genetic deletion of TRPV1 protects mice against pancreatitis. Pancreas, 2008, 36(4): 394-401.
23. Schwartz ES, Christianson JA, Chen X, et al. Synergistic role of TRPV1 and TRPA1 in pancreatic pain and inflammation. Gastroenterology, 2011, 140(4): 1283-1291.
24. Terada Y, Fujimura M, Nishimura S, et al. Contribution of TRPA1 as a downstream signal of proteinase-activated receptor-2 to pancreatic pain. J Pharmacol Sci, 2013, 123(3): 284-287.
25. Kanju P, Chen Y, Lee W, et al. Small molecule dual-inhibitors of TRPV4 and TRPA1 for attenuation of inflammation and pain. Sci Rep, 2016, 6: 26894. doi: 10.1038/srep26894.
26. Swain SM, Romac JM, Shahid RA, et al. TRPV4 channel opening mediates pressure-induced pancreatitis initiated by Piezo1 activation. J Clin Invest, 2020, 130(5): 2527-2541.
27. Steinhoff MS, von Mentzer B, Geppetti P, et al. Tachykinins and their receptors: contributions to physiological control and the mechanisms of disease. Physiol Rev, 2014, 94(1): 265-301.
28. Ramnath RD, Sun J, Bhatia M. Involvement of SRC family kinases in substance P-induced chemokine production in mouse pancreatic acinar cells and its significance in acute pancreatitis. J Pharmacol Exp Ther, 2009, 329(2): 418-428.
29. Koh YH, Tamizhselvi R, Moochhala S, et al. Role of protein kinase C in caerulein induced expression of substance P and neurokinin-1-receptors in murine pancreatic acinar cells. J Cell Mol Med, 2011, 15(10): 2139-2149.
30. Li B, Han X, Ye X, et al. Substance P-regulated leukotriene B4 production promotes acute pancreatitis-associated lung injury through neutrophil reverse migration. Int Immunopharmacol, 2018, 57: 147-156.
31. Ramnath RD, Bhatia M. Substance P treatment stimulates chemokine synthesis in pancreatic acinar cells via the activation of NF-kappaB. Am J Physiol Gastrointest Liver Physiol, 2006, 291(6): G1113-G1119.
32. Han C, Du D, Wen Y, et al. Chaiqin chengqi decoction ameliorates acute pancreatitis in mice via inhibition of neuron activation-mediated acinar cell SP/NK1R signaling pathways. J Ethnopharmacol, 2021, 274: 114029. doi: 10.1016/j.jep.2021.114029.
33. Russell FA, King R, Smillie SJ, et al. Calcitonin gene-related peptide: physiology and pathophysiology. Physiol Rev, 2014, 94(4): 1099-1142.
34. Sternini C, Brecha N. Immunocytochemical identification of islet cells and nerve fibers containing calcitonin gene-related peptide-like immunoreactivity in the rat pancreas. Gastroenterology, 1986, 90(5 Pt 1): 1155-1163.
35. Warzecha Z, Dembiński A, Ceranowicz P, et al. The influence of sensory nerves and CGRP on the pancreatic regeneration after repeated episodes of acute pancreatitis in rats. J Physiol Pharmacol. 2000, 51(3): 449-461.
36. Warzecha Z, Dembiński A, Ceranowicz P, et al. Protective effect of calcitonin gene-related peptide against caerulein-induced pancreatitis in rats. J Physiol Pharmacol. 1997, 48(4): 775-787.
37. Warzecha Z, Dembiński A, Ceranowicz P, et al. Calcitonin gene-related peptide can attenuate or augment pancreatic damage in caerulein-induced pancreatitis in rats. J Physiol Pharmacol. 1999, 50(1): 49-62.
38. Wick EC, Pikios S, Grady EF, et al. Calcitonin gene-related peptide partially mediates nociception in acute experimental pancreatitis. Surgery, 2006, 139(2): 197-201.
39. Nishimura S, Fukushima O, Ishikura H, et al. Hydrogen sulfide as a novel mediator for pancreatic pain in rodents. Gut, 2009, 58(6): 762-770.
40. Terada Y, Fujimura M, Nishimura S, et al. Roles of Cav3. 2 and TRPA1 channels targeted by hydrogen sulfide in pancreatic nociceptive processing in mice with or without acute pancreatitis. J Neurosci Res, 2015, 93(2): 361-369.
41. Qiu Y, Huang L, Fu J, et al. TREK channel family activator with a well-defined structure-activation relationship for pain and neurogenic inflammation. J Med Chem, 2020, 63(7): 3665-3677.
42. Li J, Liu Y, Yuan L, et al. A tissue-like neurotransmitter sensor for the brain and gut. Nature, 2022, 606(7912): 94-101.
43. Zhang Q, Ren Y, Mo Y, et al. Inhibiting Hv1 channel in peripheral sensory neurons attenuates chronic inflammatory pain and opioid side effects. Cell Res, 2022, 32(5): 461-476.
44. Beaulieu-Laroche L, Christin M, Donoghue A, et al. TACAN is an ion channel involved in sensing mechanical pain. Cell, 2020, 180(5): 956-967.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Neurogenic inflammation and pain in acute pancreatitis

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