Skip to main content

Advertisement

SpringerLink
Log in

Tachykinin Peptide, Substance P, and Its Receptor NK-1R Play an Important Role in Alimentary Tract Mucosal Inflammation During Cytotoxic Therapy

  • Review
  • Published:
Digestive Diseases and Sciences Aims and scope Submit manuscript

Abstract

The alimentary tract mucosal inflammation has been a topic of concern in oncology; though many modalities of treatment have been proposed for mucosal inflammation, the contributing adverse effects have severely affected the quality of life of patients. This review focuses on the importance of neurogenic peptide, Substance P and its receptor NK-1R in modulating the cascades of events in mucosal inflammation during cytotoxic therapy. There are various preclinical and clinical models showing increased expression of Substance P/NK-1R in ionizing radiation and chemotherapy, but only very few preclinical studies to our knowledge have highlighted or examined its role in mucosal inflammation. Hence, the importance of neuropeptide involved in the inflammatory events in mucosal inflammation in cytotoxic therapy could be a major breakthrough for future research purposes and treatment. The factors contributing to the severity of tissue reactions have been multietiogenic; thus, resultant treatment also has to be directed toward multiple contributing factors. This review also focuses on the significance of care strategy to be adopted in alimentary tract mucositis when multietiogenic factors are taken into consideration.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Elting LS, Cooksley CD, Chambers MS, Garden AS. Risk, outcomes, and costs of radiation-induced oral mucositis among patients with head-and-neck malignancies. Int J Radiat Oncol Biol Phys. 2007;68:1110–1120.

    Article  PubMed  Google Scholar 

  2. Kim JW, Cha Y, Kim SJ, et al. Association of oral mucositis with quality of life and symptom clusters in patients with solid tumors receiving chemotherapy. Support Care Cancer. 2012;20:395–403.

    Article  PubMed  Google Scholar 

  3. Trotti A, Bellm LA, Epstein JB, et al. Mucositis incidence, severity and associated outcomes in patients with head and neck cancer receiving radiotherapy with or without chemotherapy: a systematic literature review. Cancer. 2008;113:2704–2713.

    Article  Google Scholar 

  4. Sonis ST. Oral mucositis in head and neck cancer. Am Soc Clin Oncol Educ Book. 2013;2013:236–240.

    Article  Google Scholar 

  5. Sonis ST. A biological approach to mucositis. J Support Oncol. 2004;2:21–32.

    PubMed  Google Scholar 

  6. Chen L, Hu CS, Chen XZ, et al. Concurrent chemoradiotherapy plus adjuvant chemotherapy versus concurrent chemoradiotherapy alone in patients with locoregionally advanced nasopharyngeal carcinoma: a phase 3 multicentre randomised controlled trial. Lancet Oncol. 2012;13:163–171.

    Article  PubMed  Google Scholar 

  7. Lee AW, Tung SY, Chua DT, et al. Randomized trial of radiotherapy plus concurrent-adjuvant chemotherapy vs radiotherapy alone for regionally advanced nasopharyngeal carcinoma. J Natl Cancer Inst. 2010;102:1188–1198.

    Article  PubMed  Google Scholar 

  8. Al-Dasooqi N, Sonis ST, Bowen JM, et al. Emerging evidence on the pathobiology of mucositis. Support Care Cancer. 2013;21:2075–2083.

    Article  PubMed  Google Scholar 

  9. Matsumoto K, Nakajima T, Sakai H, et al. Increased expression of 5-HT3 and NK 1 receptors in 5-fluorouracil-induced mucositis in mouse jejunum. Dig Dis Sci. 2013;58:3440–3451.

    Article  CAS  PubMed  Google Scholar 

  10. Höckerfelt U, Franzén L, Kjörell U, Forsgren S. Parallel increase in substance P and VIP in rat duodenum in response to irradiation. Peptides. 2000;21:271–281.

    Article  PubMed  Google Scholar 

  11. Höckerfelt U, Franzén L, Forsgren S. Substance P (NK1) receptor in relation to substance P innervation in rat duodenum after irradiation. Regul Pept. 2001;98:115–126.

    Article  PubMed  Google Scholar 

  12. Forsgren S, Höckerfelt U, Norrgård O, Henriksson R, Franzén L. Pronounced substance P innervation in irradiation-induced enteropathy—a study on human colon. Regul Pept. 2000;88:1–13.

    Article  CAS  PubMed  Google Scholar 

  13. Hesketh PJ, Grunberg SM, Gralla RJ, et al. The oral neurokinin-1 antagonist aprepitant for the prevention of chemotherapy-induced nausea and vomiting: a multinational, randomized, double-blind, placebo-controlled trial in patients receiving high-dose cisplatin—the Aprepitant protocol 052 study group. J Clin Oncol. 2003;21:4112–4119.

    Article  CAS  PubMed  Google Scholar 

  14. Poli-Bigelli S, Rodrigues-Pereira J, Carides AD, et al. Addition of the neurokinin 1 receptor antagonist aprepitant to standard antiemetic therapy improves control of chemotherapy-induced nausea and vomiting. Results from a randomized, double-blind, placebo-controlled trial in Latin America. Cancer. 2003;97:3090–3098.

    Article  CAS  PubMed  Google Scholar 

  15. Warr DG, Hesketh PJ, Gralla RJ, et al. Efficacy and tolerability of aprepitant for the prevention of chemotherapy-induced nausea and vomiting in patients with breast cancer after moderately emetogenic chemotherapy. J Clin Oncol. 2005;23:2822–2830.

    Article  CAS  PubMed  Google Scholar 

  16. Koon HW, Pothoulakis C. Immunomodulatory properties of substance P: the gastrointestinal system as a model. Ann N Y Acad Sci. 2006;1088:23–40.

    Article  CAS  PubMed  Google Scholar 

  17. Gerard NP, Garraway LA, Eddy RL Jr, et al. Human substance P receptor (NK-1): organization of the gene, chromosome localization, and functional expression of cDNA clones. Biochemistry. 1991;30:10640–10646.

    Article  CAS  PubMed  Google Scholar 

  18. Harrison S, Geppetti P. Substance p. Int J Biochem Cell Biol. 2001;33:555–576.

    Article  CAS  PubMed  Google Scholar 

  19. Datar P, Srivastava S, Coutinho E, Govil G. Substance P: structure, function, and therapeutics. Curr Top Med Chem. 2004;4:75–103.

    Article  CAS  PubMed  Google Scholar 

  20. O’Connor TM, O’Connell J, O’Brien DI, Goode T, Bredin CP, Shanahan F. The role of substance P in inflammatory disease. J Cell Physiol. 2004;201:167–180.

    Article  PubMed  Google Scholar 

  21. González Moles MA, Esteban F, Ruiz-Avila I, et al. A role for the substance P/NK-1 receptor complex in cell proliferation and apoptosis in oral lichen planus. Oral Dis. 2009;15:162–169.

  22. Evangelista S. Involvement of tachykinins in intestinal inflammation. Curr Pharm Des. 2001;7:19–30.

    Article  CAS  PubMed  Google Scholar 

  23. Carter MS, Krause JE. Structure, expression, and some regulatory mechanisms of the rat preprotachykinin gene encoding substance P, neurokinin A, neuropeptide K, and neuropeptide gamma. J Neurosci. 1990;10:2203–2214.

    CAS  PubMed  Google Scholar 

  24. Zhang Y, Lu L, Furlonger C, Wu GE, Paige CJ. Hemokinin is a hematopoietic-specific tachykinin that regulates B lymphopoiesis. Nat Immunol. 2000;1:392–397.

    Article  CAS  PubMed  Google Scholar 

  25. Dornan WA, Vink KL, Malen P, Short K, Struthers W, Barrett C. Site-specific effects of intracerebral injections of three neurokinins (neurokinin A, neurokinin K, and neurokinin gamma) on the expression of male rat sexual behavior. Physiol Behav. 1993;54:249–258.

    Article  CAS  PubMed  Google Scholar 

  26. Duffy RA, Hedrick JA, Randolph G, et al. Centrally administered Hemokinin-1 (HK-1), a neurokinin NK1 receptor agonist, produces substance P-like behavioral effects in mice and gerbils. Neuropharmacology. 2003;45:242–250.

    Article  CAS  PubMed  Google Scholar 

  27. Sonis ST. Mucositis as a biological process: a new hypothesis for the development of chemotherapy-induced stomatotoxicity. Oral Oncol. 1998;34:39–43.

    Article  CAS  PubMed  Google Scholar 

  28. Sonis ST, Elting LS, Keefe D, et al. Perspectives on cancer therapy-induced mucosal injury: pathogenesis, measurement, epidemiology, and consequences for patients. Cancer. 2004;100:1995–2025.

    Article  PubMed  Google Scholar 

  29. Sonis ST. The biologic role for nuclear factor-kappa B in disease and its potential involvement in mucosal injury associated with anti-neoplastic therapy. Crit Rev Oral Biol Med. 2002;13:380–389.

    Article  PubMed  Google Scholar 

  30. Logan RM, Gibson RJ, Sonis ST, Keefe DMK. Nuclear factor-κB (NF-κB) and cyclooxygenase-2 (COX-2) expression in the oral mucosa following cancer chemotherapy. Oral Oncol. 2007;43:395–401.

    Article  CAS  PubMed  Google Scholar 

  31. Sonis ST. Oral mucositis. Anticancer Drugs. 2011;22:607–612.

    Article  CAS  PubMed  Google Scholar 

  32. Kozakiewicz M, Godlewski A. Modulation of the mitotic activity and population of the mast cells in the oral mucosa by substance P. Cell Mol Biol Lett. 2003;8:727–734.

    CAS  PubMed  Google Scholar 

  33. Aalto Y, Forsgren S, Kjörell U, Franze´n L, Gustafsson H, Henriksson R. Time- and dose-related changes in the expression of substance P in salivary glands in response to fractionated irradiation. Int J Radiat Oncol Biol Phys. 1995;33:297–305.

  34. Forsgren S, Franzén L, Funegård U, Gustafsson H, Henriksson R. Bilateral irradiation of head and neck induces an enhanced expression of substance P in the parasympathetic innervation of the submandibular gland. Neuroscience 1992;46:233–240.

  35. Lidegran M, Domeij S, Dalqvist Å, et al. Irradiation influences the expression of substance P and enkephalin in the rat larynx. Cell Tissue Res. 1995;279:55–63.

    Article  CAS  PubMed  Google Scholar 

  36. Alfieri AB, Cubeddu LX. Efectos de los antagonistas de los receptors NK1 y de la dexametasona sobre la inflamación neurogénica inducida porciclofosfamida y por radiación X, en la rata. AVFT. 2004;23:61–66.

    Google Scholar 

  37. Goode T, O’Connell J, Sternini C, et al. Substance P (neurokinin-1) receptor is a marker of human mucosal but not peripheral mononuclear cells: molecular quantitation and localization. J Immunol. 1998;161:2232–2240.

    CAS  PubMed  Google Scholar 

  38. Pothoulakis C, Castagliuolo I, Leeman SE, et al. Substance P receptor expression in intestinal epithelium in clostridium difficile toxin A enteritis in rats. Am J Physiol. 1998;275:G68–G75.

    CAS  PubMed  Google Scholar 

  39. Andrews PLR, Rudd JA. The role of tachykinins and the tachykinin NK1 receptor in nausea and emesis. In: Hofmann FB, ed. Handbook of experimental pharmacology. Berlin: Springer; 2004:359–440.

    Google Scholar 

  40. González Moles MA, Mosqueda-Taylor A, Esteban F et al. Cell proliferation associated with actions of the substance P/NK-1 receptor complex in keratocystic odontogenic tumours. Oral Oncol. 2008; 44:1127–1133.

  41. Kabashima H, Nagata K, Maeda K, Iijima T. Involvement of substance P, mast cells, TNF-alpha and ICAM-1 in the infiltration of inflammatory cells in human periapical granulomas. J Oral Pathol Med. 2002;31:175–180.

    Article  CAS  PubMed  Google Scholar 

  42. Cocchiara R, Albeggiani G, Azzolina A, et al. Effect of Substance P on uterine mast cell cytokine release during the reproductive cycle. J Neuroimmunol. 1995;60:107–115.

    Article  CAS  PubMed  Google Scholar 

  43. Cocchiara R, Bongiovanni A, Albeggiani G, et al. Inhibitory effect of neuraminidase on SP-induced histamine release and TNF-α mRNA: evidence of a receptor-independent mechanism. J Neuroimmunol. 1997;75:9–18.

    Article  CAS  PubMed  Google Scholar 

  44. Kaltschmidt B, Baeuerle PA, Kaltschmidt C. Potential involvement of the transcription factor NF-kappa B in neurological disorders. Mol Aspects Med. 1993;14:171–190.

    Article  CAS  PubMed  Google Scholar 

  45. Azzolina A, Bongiovanni A, Lampiasi N. Substance P induces TNF-alpha and IL-6 production through NF kappa B in peritoneal mast cells. Biochim Biophys Acta Mol Cell Res. 2003;1643:75–83.

    Article  CAS  Google Scholar 

  46. Cocchiara R, Bongiovanni A, Albeggiani G, Azzolina A, Geraci D. Substance P selectively activates TNF-alpha mRNA in rat uterine immune cells: a neuroimmune link. NeuroReport. 1997;8:2961–2964.

    Article  CAS  PubMed  Google Scholar 

  47. Azzolina A, Guarneri P, Lampiasi N. Involvement of p38 and JNK MAPKs pathways in substance P-induced production of the TNF-α by peritoneal mast cells. Cytokine. 2002;18:72–80.

    Article  CAS  PubMed  Google Scholar 

  48. Ishizuka T, Terada N, Gerwins P, et al. Mast cells tumor necrosis factor alpha production is regulated by MEK kinases. Proc Natl Acad Sci. 1997;94:6358–6363.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  49. Lorenz D, Wiesner B, Zipper J, et al. Mechanism of peptide-induced mast cell degranulation. Translocation and patch-clamp studies. J Gen Physiol. 1998;112:577–591.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  50. Ferry X, Eichwald V, Daeffler L, Landry Y. Activation of betagamma subunits of Gi2 and Gi3 proteins by basic secretagogues induces exocytosis through phospholipases cβ and arachidonate release through phospholipase Cgamma in mast cells. J Immunol. 2001;167:4805–4813.

    Article  CAS  PubMed  Google Scholar 

  51. Page S, Fischer C, Baumgartner B, et al. 4-Hydroxynonenal prevents NFκB activation and tumor necrosis factor expression by inhibiting IκB phosphorylation and subsequent proteolysis. J Biol Chem. 1999;274:11611–11618.

    Article  CAS  PubMed  Google Scholar 

  52. Pelletier C, Varin-Blank N, Rivera J, et al. FcεRI-mediated induction of TNF-α gene expression in the RBL-2H3 mast cell line: regulation by a novel NFκB-like nuclear binding complex. J Immunol. 1998;161:4768–4776.

    CAS  PubMed  Google Scholar 

  53. Al-Dasooqi N, Gibson RJ, Bowen JM, Logan RM, Stringer AM, Keefe DM. Matrix metalloproteinases are possible mediators for the development of alimentary tract mucositis in the dark agouti rat. Exp Biol Med (Maywood). 2010;235:1244–1256.

    Article  CAS  Google Scholar 

  54. Cury PR, Canavez F, de Araújo VC, Furuse C, de Araújo NS. Substance P regulates the expression of matrix metalloproteinases and tissue inhibitors of metalloproteinase in cultured human gingival fibroblasts. J Periodontal Res. 2008;43:255–260.

    Article  CAS  PubMed  Google Scholar 

  55. Carter AB, Knudtson KL, Monick MM, Hunninghake GW. The p38 mitogen-activated protein kinase is required for NF-kappaB-dependent gene expression. The role of TATA-binding protein (TBP). J Biol Chem. 1999;274:30858–30863.

    Article  CAS  PubMed  Google Scholar 

  56. Zampetaki A, Mitsialis SA, Pfeilschifter J, Kourembanas S. Hypoxia induces macrophage inflammatory protein-2 (MIP-2) gene expression in murine macrophages via NF-kappaB: the prominent role of p42/p44 and PI3 kinase pathways. FASEB J. 2004;18:1090–1092.

    CAS  PubMed  Google Scholar 

  57. Chang L, Karin M. Mammalian MAP kinase signalling cascades. Nature. 2001;410:37–40.

    Article  CAS  PubMed  Google Scholar 

  58. Deak M, Clifton AD, Lucocq LM, Alessi DR. Mitogen- and stress-activated protein kinase-1 (MSK1) is directly activated by MAPK and SAPK2/p38, and may mediate activation of CREB. EMBO J. 1998;17:4426–4441.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  59. Kefaloyianni E, Gaitanaki C, Beis I. ERK1/2 and p38-MAPK signalling pathways, through MSK1, are involved in NF-kappaB transactivation during oxidative stress in skeletal myoblasts. Cell Signal. 2006;18:2238–2251.

    Article  CAS  PubMed  Google Scholar 

  60. Kyriakis JM, Avruch J. Mammalian mitogen-activated protein kinase signal transduction pathways activated by stress and inflammation. Physiol Rev. 2001;81:807–869.

    CAS  PubMed  Google Scholar 

  61. Alarcon-Vargas D, Ronai Z. c-Jun-NH2 kinase (JNK) contributes to the regulation of c-Myc protein stability. J Biol Chem. 2004;279:5008–5016.

    Article  CAS  PubMed  Google Scholar 

  62. Sabapathy K, Hochedlinger K, Nam SY, Bauer A, Karin M, Wagner EF. Distinct roles for JNK1 and JNK2 in regulating JNK activity and c-Jun-dependent cell proliferation. Mol Cell. 2004;15:713–725.

    Article  CAS  PubMed  Google Scholar 

  63. Raman M, Chen W, Cobb MH. Differential regulation and properties of MAPKs. Oncogene. 2007;26:3100–3112.

    Article  CAS  PubMed  Google Scholar 

  64. Kyriakis JM, Avruch J. Mammalian MAPK signal transduction pathways activated by stress and inflammation: a 10-year update. Physiol Rev. 2012;92:689–737.

    Article  CAS  PubMed  Google Scholar 

  65. Chen Z, Gibson TB, Robinson F, et al. MAP kinases. Chem Rev. 2001;101:2449–2476.

    Article  CAS  PubMed  Google Scholar 

  66. Sun J, Ramnath RD, Zhi L, Tamizhselvi R, Bhatia M. Substance P enhances NF-kappaB transactivation and chemokine response in murine macrophages via ERK1/2 and p38 MAPK signaling pathways. Am J Physiol Cell Physiol. 2008;294:C1586–C1596.

    Article  CAS  PubMed  Google Scholar 

  67. Maes M, Lin AH, Delmeire L, et al. Elevated serum interleukin-6 (IL-6) and IL-6 receptor concentrations in posttraumatic stress disorder following accidental man-made traumatic events. Biol Psychiatry. 1999;45:833–839.

    Article  CAS  PubMed  Google Scholar 

  68. Powell ND, Tarr AJ, Sheridan JF. Psychosocial stress and inflammation in cancer. Brain Behav Immun. 2013;30:S41–S47.

    Article  CAS  PubMed  Google Scholar 

  69. Peters EM, Liotiri S, Bodo E, et al. Probing the effects of stress mediators on the human hair follicle: substance P holds central position. Am J Pathol. 2007;171:1872–1886.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  70. Chancellor-Freeland C, Zhu GF, Kage R, Beller DI, Leeman SE, Black PH. Substance P and stress-induced changes in macrophages. Ann N Y Acad Sci. 1995;771:472–484.

    Article  CAS  PubMed  Google Scholar 

  71. Paus R, Heinzelmann T, Schultz KD, Furkert J, Fechner K, Czar-netzki BM. Hair growth induction by substance P. Lab Invest. 1994;71:134–140.

    CAS  PubMed  Google Scholar 

  72. Peters EM, Botchkarev VA, Botchkareva NV, Tobin DJ, Paus R. Hair-cycle-associated remodelling of the peptidergic innervation of murine skin, and hair growth modulation by neuropeptides. J Invest Dermatol. 2001;116:236–245.

    Article  CAS  PubMed  Google Scholar 

  73. Peters EM, Kuhlmei A, Tobin DJ, Muller-Rover S, Klapp BF, Arck PC. Stress exposure modulates peptidergic innervation and degranulates mast cells in murine skin. Brain Behav Immun. 2005;19:252–262.

    Article  CAS  PubMed  Google Scholar 

  74. Rice FL, Fundin B T, Arvidsson J, Aldskogius H, Johansson O. Comprehensive immunofluorescence and lectin binding analysis of vibrissal follicle sinus complex innervation in the mystacial pad of the rat. J Comp Neurol. 1997: 385:149–184.

  75. Arck PC, Handjiski B, Peters EM, et al. Stress inhibits hair growth in mice by induction of premature catagen development and deleterious perifollicular inflammatory events via neuropeptide substance P-dependent pathways. Am J Pathol. 2003;162:803–814.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  76. Raithel M, Schneider HT, Hahn EG. Effect of substance P on histamine secretion from gut mucosa in inflammatory bowel disease. Scand J Gastroenterol. 1999;34:496–503.

    Article  CAS  PubMed  Google Scholar 

  77. Mantyh PW, Catton M, Maggio JE, Vigna SR. Alterations in receptors for sensory neuropeptides in human inflammatory bowel disease. Adv Exp Med Biol. 1991;298:253–283.

    Article  CAS  PubMed  Google Scholar 

  78. Mazumdar S, Das KM. Immunocytochemical localization of vasoactive intestinal peptide and substance P in the colon from normal subjects and patients with inflammatory bowel disease. Am J Gastroenterol. 1992;87:176–181.

    CAS  PubMed  Google Scholar 

  79. Newson B, Dahlstrom A, Enerbäck L, Ahlman H. Suggestive evidence for a direct innervation of mucosal mast cells. Neuroscience. 1983;10:565–570.

    Article  CAS  PubMed  Google Scholar 

  80. Goyal RK, Hirano I. The enteric nervous system. N Engl J Med. 1996;334:1106–1115.

    Article  CAS  PubMed  Google Scholar 

  81. Farhadi A, Fields JZ, Keshavarzian A. Mucosal mast cells are pivotal elements in inflammatory bowel disease that connect the dots: stress, intestinal hyperpermeability and inflammation. World J Gastroenterol. 2007;13:3027–3030.

    PubMed Central  PubMed  Google Scholar 

  82. Barbara G, Stanghellini V, De Giorgio R, et al. Activated mast cells in proximity to colonic nerves correlate with abdominal pain in irritable bowel syndrome. Gastroenterology. 2004;126:693–702.

    Article  PubMed  Google Scholar 

  83. He SH. Key role of mast cells and their major secretory products in inflammatory bowel disease. World J Gastroenterol. 2004;10:309–318.

    CAS  PubMed  Google Scholar 

  84. Carrasco GA, Van de Kar LD. Neuroendocrine pharmacology of stress. Eur J Pharmacol. 2003;463:235–272.

    Article  CAS  PubMed  Google Scholar 

  85. Schemann M. Control of gastrointestinal motility by the “gut brain”—the enteric nervous system. J Pediatr Gastroenterol Nutr. 2005;41:S4–S6.

    Article  PubMed  Google Scholar 

  86. Ader R, Cohen N, Felten D. Psychoneuroimmunology: interactions between the nervous system and the immune system. Lancet. 1995;345:99–103.

    Article  CAS  PubMed  Google Scholar 

  87. Mayer EA. The neurobiology of stress and gastrointestinal disease. Gut. 2000;47:861–869.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  88. Reichlin S. Neuroendocrine-immune interactions. N Engl J Med. 1993;329:1246–1253.

    Article  CAS  PubMed  Google Scholar 

  89. Mawdsley JE, Rampton DS. Psychological stress in IBD: new insights into pathogenic and therapeutic implications. Gut. 2005;54:1481–1491.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  90. Barnes PJ. Molecular mechanisms of corticosteroids in allergic diseases. Allergy. 2001;56:928–936.

    Article  CAS  PubMed  Google Scholar 

  91. Ray A, Sehgal PB. Cytokines and their receptors: molecular mechanism of interleukin-6 gene repression by glucocorticoids. J Am Soc Nephrol. 1992;2:S214–S221.

    CAS  PubMed  Google Scholar 

  92. Joyce DA, Gimblett G, Steer JH. Targets of glucocorticoid action on TNF- alpha release by macrophages. Inflamm Res. 2001;50:337–340.

    Article  CAS  PubMed  Google Scholar 

  93. Franchimont D, Kino T, Galon J, Meduri GU, Chorousos G. Glucocorticoids and inflammation revisited: the state of the art. NIH Clinical Staff Conference. Neuroimmunomodulation 2002–2003;10:247–260.

  94. Yamaguchi M, Takizawa T, Nakajima R, Imamura R, Kasai. The Damon System and release of substance P in gingival crevicular fluid during orthodontic tooth movement in adults. World J Orthod.. 2009;10:141–146.

    PubMed  Google Scholar 

  95. Caviedes-Bucheli J, Azuero-Holguin MM, Gutierrez-Sanchez L, et al. The effect of three different rotary instrumentation systems on substance P and calcitonin gene-related peptide expression in human periodontal ligament. J Endod. 2010;36:1938–1942.

    Article  PubMed  Google Scholar 

  96. Herpfer I, Lieb K. Substance P receptor antagonists in psychiatry: rationale for development and therapeutic potential. CNS Drugs. 2005;19:275–293.

    Article  CAS  PubMed  Google Scholar 

  97. Pike JL, Smith TL, Hauger RL, et al. Chronic life stress alters sympathetic, neuroendocrine, and immune responsivity to an acute psychological stressor in humans. Psychosom Med. 1997;59:447–457.

    Article  CAS  PubMed  Google Scholar 

  98. Liu L, Markus I, Saghire HE, Perera DS, King DW, Burcher E. Gene expression in ulcerative colitis, Crohn’s disease and diverticular disease: a role for hemokinin-1? Neurogastroenterol Motil. 2011;23:475–483 (e179–1e80).

  99. Morse HR, Olomolaiye OO, Wood NA, Keen LJ, Bidwell JL. Induced heteroduplex genotyping of TNF-alpha, IL-1beta, IL-6 and IL-10 polymorphisms associated with transcriptional regulation. Cytokine. 1999;11:789–795.

    Article  CAS  PubMed  Google Scholar 

  100. Andreassen CN, Alsner J, Overgaard J. Does variability in normal tissue reactions after radiotherapy have a genetic basis—where and how to look for it? Radiother Oncol. 2002;64:131–140.

    Article  PubMed  Google Scholar 

  101. Stringer AM. Interaction between host cells and microbes in chemotherapy-induced mucositis. Nutrients.. 2013;5:1488–1499.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  102. Stringer AM, Gibson RJ, Logan RM, et al. Gastrointestinal microflora and mucins may play a critical role in the development of 5-Fluorouracil-induced gastrointestinal mucositis. Exp Biol Med (Maywood).. 2009;234:430–441.

    Article  CAS  PubMed  Google Scholar 

  103. Sonis ST. The pathobiology of mucositis. Nat Rev Cancer. 2004;4:277–284.

    Article  CAS  PubMed  Google Scholar 

  104. Graham GJ, Stevens JM, Page NM, et al. Tachykinins regulate the function of platelets. Blood. 2004;104:1058–1065.

    Article  CAS  PubMed  Google Scholar 

  105. Esteban F, Munoz M, Gonzalez-Moles MA, Rosso M. A role for substance P in cancer promotion and progression: a mechanism to counteract intracellular death signals following oncogene activation or DNA damage. Cancer Metastasis Rev. 2006;25:137–145.

    Article  CAS  PubMed  Google Scholar 

  106. Esteban F, Gonzalez-Moles MA, Castro D, et al. Expression of substance P and neurokinin-1-receptor in laryngeal cancer: linking chronic inflammation to cancer promotion and progression. Histopathology. 2009;54:258–260.

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

No grant support and no financial arrangements related to the research or assistance with manuscript preparation.

Conflict of interest

None.

Author information

Authors and Affiliations

  1. Department of Oncology and Palliative Medicine, Velindre Hospital, Cardiff University, Wales, CF 14 2TL, UK

    P. S. Satheeshkumar

  2. Department of Oral Medicine, Mar Baselios Dental College, Kerala University of Health Sciences, Kerala, 686691, India

    P. S. Satheeshkumar & Minu P. Mohan

Authors
  1. P. S. Satheeshkumar
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Minu P. Mohan
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to P. S. Satheeshkumar.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Satheeshkumar, P.S., Mohan, M.P. Tachykinin Peptide, Substance P, and Its Receptor NK-1R Play an Important Role in Alimentary Tract Mucosal Inflammation During Cytotoxic Therapy. Dig Dis Sci 59, 2864–2873 (2014). https://doi.org/10.1007/s10620-014-3263-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10620-014-3263-7

Keywords

Search

Navigation