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Pain and pain generation in pancreatic cancer

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Abstract

Background

Pain can be a frequent symptom during the natural history of a patient with pancreatic cancer. An increase in incidence with disease progression and the presence of unbearable pain may preclude a curative resection.

Materials and methods

Even in those patients with resectable pancreatic cancer, the presence of pain has an impact on prognosis. To date, we do not really know why some patients develop pain.

Results

Perineural cancer cell invasion is one of the most intriguing characteristics of this neoplasia and may in some cases explain the pain sensation. In addition, so-called “neurogenic inflammation” might also play a role in pain generation in pancreatic cancer, just like in chronic pancreatitis.

Conclusion

In conclusion, understanding the mechanisms of pain in pancreatic cancer could help patients because what counts is not only 5-year survival but also median survival with good quality of life.

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References

  1. Kleeff J, Michalski C, Friess H, Büchler MW (2006) Pancreatic cancer: from bench to 5-year survival. Pancreas 33(2):111–118

    Article  PubMed  CAS  Google Scholar 

  2. Beger HG, Rau B, Gansauge F, Poch B, Link KH (2003) Treatment of pancreatic cancer: challenge of the facts. World J Surg 27(10):1075–1084

    Article  PubMed  Google Scholar 

  3. Puor PM, Weide L, Liu G, Kazakoff K, Scheetz M, Toshkov I, Ikematsu Y, Fienhold MA, Sanger W (1997) Experimental evidence for the origin of ductal-type adenocarcinoma from the islet of Langerhans. Am J Pathol 150:2167–2180

    Google Scholar 

  4. Pour PM, Bell RH, Batra SK (2003) Neural invasion in the staging of pancreatic cancer. Pancreas 26(4):322–325

    Article  PubMed  Google Scholar 

  5. Larson DL, Rodin AE, Roberts DK, O’Steen WK, Rapperport AS, Lewis SR (1966) Perineural lymphatics: myth or fact. Am J Surg 106:488–492

    Article  Google Scholar 

  6. Bockman DE, Büchler MW, Beger HG (1994) Interaction of pancreatic ductal carcinoma with nerves leads to nerve damage. Gastroenterology 107:219–230

    PubMed  CAS  Google Scholar 

  7. Kenmotsu M (1990) Relationship between perineural invasion and expression of neuroendocrine markers and neural cell adhesion molecule in human pancreatic carcinoma. Jpn J Gastroenterol Surg 23:2580–2585

    Google Scholar 

  8. Seki H, Tanaka J-I, Sato Y, Kato Y, Umezawa A, Koyama K (1993) Neural cell adhesion molecule (NCAM) and perineural invasion in bile duct cancer. J Surg Oncol l53:78–83

    Article  Google Scholar 

  9. Zhu Z, Friess H, di Mola FF, Zimmermann A, Graber HU, Korc M, Büchler MW (1999) Nerve growth factor expression correlates with perineural invasion and pain in human pancreatic cancer. J Clin Oncol 17(8):2419–28

    PubMed  CAS  Google Scholar 

  10. Lindsay TH, Jonas BM, Sevcik MA, Kubota K, Halvorson KG, Ghilardi JR, Kuskowski MA, Stelow EB, Mukherjee P, Gendler SJ, Wong GY, Mantyh PW (2005) Pancreatic cancer pain and its correlation with changes in tumor vasculature, macrophage infiltration, neuronal innervation, body weight and disease progression. Pain 119(1–3):233–246

    Article  PubMed  CAS  Google Scholar 

  11. Bowles WR, Sabino M, Harding-Rose C, Hargreaves KM (2006) Chronic nerve growth factor administration increases the peripheral exocytotic activity of capsaicin-sensitive cutaneous neurons. Neurosci Lett 403(3):305–308

    Article  PubMed  CAS  Google Scholar 

  12. Grelik C, Allard S, Ribeiro-da-Silva A (2005) Changes in nociceptive sensory innervation in the epidermis of the rat lower lip skin in a model of neuropathic pain. Neurosci Lett 389(3):140–5

    Article  PubMed  CAS  Google Scholar 

  13. Aggarwal BB, Shishodia S, Sandur SK, Pandey MK, Sethi G (2006) Inflammation and cancer: how hot is the link. Biochem Pharmacol 72(11):1605–1621

    Article  PubMed  CAS  Google Scholar 

  14. Sternini C, De Giorgio R, Anderson K, Watt PC, Brunicardi FC, Widdison AL, Wong H, Reber HA, Walsh JH, Go VL (1992) Species differences in the immunoreactive patterns of calcitonin gene-related peptide in the pancreas. Cell Tissue Res 269(3):447–458

    Article  PubMed  CAS  Google Scholar 

  15. Miyamoto Y, Maitra A, Ghosh B et al (2003) Notch mediates TGF alpha-induced changes in epithelial differentiation during pancreatic tumorigenesis. Cancer Cell 3:565–576

    Article  PubMed  CAS  Google Scholar 

  16. Buchler P, Gazdhar A, Schubert M, Giese N, Reber HA, Hines OJ, Giese T, Ceyhan GO, Muller M, Büchler MW, Friess H (2005) The Notch signaling pathway is related to neurovascular progression of pancreatic cancer. Ann Surg 242(6):791–800

    Article  PubMed  Google Scholar 

  17. Cheng L, Jia H, Lohr M, Bagherzadeh A, Holmes DI, Selwood D, Zachary I (2004) Anti-chemorepulsive effects of vascular endothelial growth factor and placental growth factor-2 in dorsal root ganglion neurons are mediated via neuropilin-1 and cyclooxygenase-derived prostanoid production. J Biol Chem 279(29):30654–30661

    Article  PubMed  CAS  Google Scholar 

  18. Ceyhan GO, Giese NA, Erkan M, Kerscher AG, Wente MN, Giese T, Büchler MW, Friess H (2006) The neurotrophic factor artemin promotes pancreatic cancer invasion. Ann Surg 244(2):274–281

    Article  PubMed  Google Scholar 

  19. Friess H, Zhu Z, di Mola FF, Kulli C, Graber HU, Andren-Sandberg A, Zimmermann A, Korc M, Rheinshager M, Büchler MW (1999) Nerve growth factor and its high-affinity receptor in chronic pancreatitis. Ann Surg 230:615–624

    Article  PubMed  CAS  Google Scholar 

  20. Esposito I, Menicagli M, Funel N, Bergmann F, Boggi U, Mosca F, Bevilacqua G, Campani D (2004) Inflammatory cells contribute to the generation of an angiogenic phenotype in pancreatic ductal adenocarcinoma. J Clin Pathol 57(6):630–636

    Article  PubMed  CAS  Google Scholar 

  21. Averill S, McMahon SB, Clary DO, Reichardt LF, Priestley JV (1995) Immunocytochemical localization of trkA receptors in chemically identified subgroups of adult rat sensory neurons. Eur J Neurosci 7(7):1484–1494

    Article  PubMed  CAS  Google Scholar 

  22. Hartel M, di Mola FF, Selvaggi F, Mascetta G, Wente MN, Felix K, Giese NA, Hinz U, Di Sebastiano P, Büchler MW, Friess H (2006) Vanilloids in pancreatic cancer: potential for chemotherapy and pain management. Gut 55(4):519–528

    Article  PubMed  CAS  Google Scholar 

  23. Anand U, Otto WR, Casula MA, Day NC, Davis JB, Bountra C, Birch R, Anand P (2006) The effect of neurotrophic factors on morphology, TRPV1 expression and capsaicin responses of cultured human DRG sensory neurons. Neurosci Lett 399(1–2):51–56

    Article  PubMed  CAS  Google Scholar 

  24. Friess H, Zhu Z, Liard V, Shi X, Shrikhande SV, Wang L, Lieb K, Korc M, Palma C, Zimmermann A, Reubi JC, Büchler MW (2003) Neurokinin-1 receptor expression and its potential effects on tumor growth in human pancreatic cancer. Lab Invest 83(5):731–742

    PubMed  CAS  Google Scholar 

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Correspondence to Pierluigi di Sebastiano.

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di Mola, F.F., di Sebastiano, P. Pain and pain generation in pancreatic cancer. Langenbecks Arch Surg 393, 919–922 (2008). https://doi.org/10.1007/s00423-007-0277-z

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  • DOI: https://doi.org/10.1007/s00423-007-0277-z

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