Gastric and Jejunal Ultrastructure in Capsaicin-Treated Rats with and without Experimental Ulcer

  • Carl J. Pfeiffer
  • Stefano Evangelista
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 298)


In recent years considerable interest has been demonstrated in defining the role and interactions of sensory nerves and neuropeptides in the gastrointestinal tract, where such afferent nerves are present and where some identical peptides occur in endocrine cells and neuronal tissues. Capsaicin (8-methyl-N-va-nillyl-6-nonenamide), the irritant principle of the Capsicum genus peppers, has been proven to be a valuable pharmacologic probe of high but not absolute selectivity for its actions on primary afferent neurons in the gastrointestinal tract and elsewhere (Maggi and Meli, 1988). Exogenous administration of capsaicin to animals selectively damages sensory afferents in the gut in a manner dependent upon dose, age of animal, etc. The damage occurs in gastric neurons containing tachykinins and calcitonin gene-related peptide, in substance P-containing afferents in anorectal mucosa, and other neurons. In the nervous system of the rat, somatostatin, substance P, and other neuropeptides are also depleted by systemic capsaicin desensitization (Gamse et al., 1984; Sternini and Brecha, 1985; Skofitsch and Jacobowitz, 1985).


Gastric Mucosa Endocrine Cell Parietal Cell Chief Cell Surface Epithelial Cell 
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  1. Brodie, D.A., Cook, P.G., Bauer, B.J., and Dagle, G.E., 1970, Indomethacin-induced intestinal lesions in the rat, Toxicol. Appl. Pharmacol. 17:615.PubMedCrossRefGoogle Scholar
  2. Ekblad, E., Ekelund, M., Graffner, H., Hakanson, R., and Sundler, F., 1985, Peptide-containing nerve fibers in the stomach wall of rat and mouse, Gastroenterology 89:73.PubMedGoogle Scholar
  3. Evangelista, S. and Meli, A., 1989, Influence of capsaicin-sensitive fibers on experimentally-induced colitis in rats, J. Pharm. Pharmacol. 41:574.PubMedCrossRefGoogle Scholar
  4. Evangelista, S., Maggi, C.A., Giuliani, S., and Meli, A., 1988, Further studies on the role of the adrenals in the capsai-cin-sensitive “gastric defense mechanism”, Int. J. Tiss. Reac. X:253.Google Scholar
  5. Evangelista, S., Maggi, C.A., and Meli, A., 1986, Evidence for a role of the adrenals in the capsaicin-sensitive “gastric defense mechanism”, Proc. Soc. Exp. Biol. Med. 182:568.PubMedGoogle Scholar
  6. Evangelista, S., Maggi, C.A., and Meli, A., 1987a, Involvement of capsaicin-sensitive mechanism(s) in the antiulcer defence of intestinal mucosa in rats, Proc. Soc. Exp. Biol. Med. 184:264.PubMedGoogle Scholar
  7. Evangelista, S., Maggi, C.A., and Meli, A., 1987b, Influence of peripherally-administered peptides on ethanol-induced gastric ulcers in the rat, Gen. Pharmac. 18:647.CrossRefGoogle Scholar
  8. Evangelista, S., Renzi, D., Mantellini, P., Surrenti, C., and Meli, A., 1989, Duodenal ulcers are associated with a depletion of duodenal calcitonin gene-related peptide-like immunoreactivity in rats, Eur. J. Pharmac. 164:389.CrossRefGoogle Scholar
  9. Farag, H.F., Abou Basha, L.M., Fikry, N., and Girgus, S., 1989, A study of the ultrastructure of the intestine of mice experimentally infected with Schistosoma mansoni and treated with praziquantel. J. Egypt. Soc. Parasitol. 19:279.PubMedGoogle Scholar
  10. Faussone-Pellegrini, M.S., Pantalone, D., and Cortesini, C., 1989, An ultrastructural study of the smooth muscle cells and nerve endings of the human stomach. J. Submicrosc. Cytol. Pathol. 21:421.PubMedGoogle Scholar
  11. Gamse, R., Leeman, S.E., Holzer, P., and Lembeck, F., 1981, Differential effects of capsaicin on the content of somatostatin, substance P and neurotensin in the nervous system of the rat. Nauyn-Schmiedeberg’s Arch. Pharmacol. 317:140.CrossRefGoogle Scholar
  12. Helmstaedter, V., Feurle, G.E., and Forssmann, W.G., 1977, Relationship of glucagon-somatostatin and gastrin-somatostatin cells in the stomach of the monkey. Cell Tiss. Res. 177:29.Google Scholar
  13. Hökfelt, T., Efendic, S., Hellerström, C. et al., 1975, Cellular localization of somatostatain in endocrine-like cells and neurons of the rat with special references to the A.,-cells of the pancreatic islets and to the hypothalamus, Acta Endocrinol. 80(Suppl. 200):1.Google Scholar
  14. Holzer, P., and Lippe, I. Th., 1988, Stimulation of afferent nerve endings by intragastric capsaicin protects against ethanol-induced damage of gastric mucosa, Neuroscience 27:981.PubMedCrossRefGoogle Scholar
  15. Holzer, P., Gamse, R., and Lembeck, F., 1980, Distribution of substance P in the rat gastrointestinal tract--lack of effect of capsaicin pretreatment, Eur. J. Pharmac. 61:303.CrossRefGoogle Scholar
  16. Holzer, P., Pabst, M.A., and Lippe, I. Th., 1989, Intragastric capsaicin protects against aspirin-induced lesion formation and bleeding in the rat gastric mucosa. Gastroenterology 96:1425.PubMedGoogle Scholar
  17. Holzer, P., and Sametz, W., 1986, Gastric mucosal protection a-gainst ulcerogenic factors in the rat mediated by capsaicin-sensitive afferent neurons, Gastroenterology 91:975.PubMedGoogle Scholar
  18. Jancsó, G., 1978, Selective degeneration of chemosensitive primary sensory neurones induced by capsaicin: glial changes, Cell Tiss. Res. 195:145.Google Scholar
  19. Jancsó, G., Király, E., and Jancsó-Gábor, A., 1977, Pharmacologically induced selective degeneration of chemosensitive primary sensory neurones. Nature 270:741.PubMedCrossRefGoogle Scholar
  20. Joo, F., Szolcsányi, J., and Jancsó-Gábor, A., 1969, Mitochondrial alterations in the spinal ganglion cells of the rat accompanying the long-lasting sensory disturbance induced by capsaicin, Life Sci. 8:621.PubMedCrossRefGoogle Scholar
  21. Kasuya, Y., Urushidani, T., and Okabe, S., 1979, Effects of various drugs and vagotomy on indomethacin-induced gastric ulcers in the rat. Jpn. J. Pharmacol. 29:670.PubMedCrossRefGoogle Scholar
  22. Kent, T.H., Cardelli, R.M., and Stamler, F.W., 1969, Small intestinal ulcers and intestinal flora in rats given indomethacin, Am. J. Pathol. 54:237.PubMedGoogle Scholar
  23. Lippe, I. Th., Pabst, M.A., and Holzer, P., 1989, Intragastric capsaicin enhances rat gastric acid elimination and mucosal blood flow by afferent nerve stimulation, Br. J., Pharmacol. 96:91.CrossRefGoogle Scholar
  24. Lundberg, J.M., Brodin, E., Hua, X., and Saria, A., 1984, Vascular permeability changes and smooth muscle contraction in relation to capsaicin-sensitive substance P afferents in the guinea-pig, Acta. Physiol. Scand. 120:217.PubMedCrossRefGoogle Scholar
  25. Maggi, C.A., and Meli, A., 1988, The sensory-efferent function of capsaicin-sensitive sensory neurons. Gen. Pharmac. 19:1.CrossRefGoogle Scholar
  26. Maggi, C.A., Evangelista, S., Abelli, L., Somma, V., and Meli, A., 1987a, Capsaicin-sensitive mechanisms and experimentally induced ulcers in rats. J. Pharm. Pharmacol. 39:559.PubMedCrossRefGoogle Scholar
  27. Maggi, C.A., Evangelista, S., Giuliani, S., and Meli, A, 1987b, Anti-ulcer activity of calcitonin gene-related peptide in rats, Gen. Pharmac. 18:33.CrossRefGoogle Scholar
  28. Okabe, S., Tabata, K., and Ishihara, Y., 1982, Indomethacin: its irritative activity on the gastrointestinal tract of experimental animals, Chpt. 3 in: “Drugs and Peptic Ulcer”, Vol. II, C.J. Pfeiffer, ed., CRC Press, Boca Raton.Google Scholar
  29. Pfeiffer, C.J., 1975, Experimental drug-induced gastric ulceration: A study of its ultrastructural component, in: “Experimental Ulcer: Models, Methods and Clinical Validity”, Gheorghiu, Th. et al., eds., G. Witzstrock, Baden-Baden.Google Scholar
  30. Pfeiffer, C.J., 1981, Experimental analysis of hydrogen ion diffusion in gastrointestinal mucus glycoprotein, Am. J. Physiol. 240:G176.Google Scholar
  31. Pfeiffer, C.J., and Roth, J.L.A., 1970, Studies on the secretory and cytotoxic actions of caffeine on the ferret gastric mucosa. Exp. Mol. Path. 13:66.CrossRefGoogle Scholar
  32. Pfeiffer, C.J., and Stephens, R.J., 1968, Ultrastructural changes of the parietal cell in the ferret gastric mucosa induced by pylorus-ligation and glucocorticoid administration. J. Ultrastruct. Res. 21:524.CrossRefGoogle Scholar
  33. Pfeiffer, C.J., and Weibel, J., 1973, The gastric mucosal response to acetylsalicylic acid in the ferret: an ultrastructural study. Am. J. Digest. Dis. 18:834.PubMedCrossRefGoogle Scholar
  34. Pfeiffer, C.J., Keith, J.C.Jr., and April, M., 1987a, Topographic localization of gastric lesions and key role of plasma bicarbonate concentration in dogs with experimentally induced gastric dilatation. Am. J. Vet. Res. 48:262.PubMedGoogle Scholar
  35. Pfeiffer, C.J., Murray, M.J., and Fainter, L., 1987b, The equine colonic mucosal granular cell: Identification and X-ray microanalysis of apical granules and nuclear bodies. Anat. Rec. 219:258.PubMedCrossRefGoogle Scholar
  36. Pfeiffer, C.J., Pfeiffer, D.C., and Szabo, S., 1987c, Early ultrastructural changes in rat duodenal mucosa associated with cysteamine-induced ulcer, Exp. Mol. Pathol. 46:102.PubMedCrossRefGoogle Scholar
  37. Pfeiffer, C.J., Rowden G., and Weibel, J., 1974, “Gastrointestinal Ultrastructure,” Academic Press, New York.Google Scholar
  38. Robert, A., 1979, Cytoprotection by prostaglandins, Gastroenterology 77:761.PubMedGoogle Scholar
  39. Scadding, J.W., 1980, The permanent anatomical effects of neonatal capsaicin on somatosensory nerves. J. Anat. 131:473.Google Scholar
  40. Skofitsch, G., and Jacobowitz, D., 1985, Calcitonin gene-related peptide coexists with substance P in capsaicin sensitive neurons and sensory ganglia of the rat, Peptides 6:747.PubMedCrossRefGoogle Scholar
  41. Sternini, C., and Brecha, N., 1985, Effect of neurotoxin treatment on calcitonin gene-related peptide-like immunoreactivity in the upper gastrointestinal tract, Gastroenterology 88:1600.Google Scholar
  42. Szabo, S. 1984, Pathogenesis of duodenal ulcer disease, Lab. Invest. 51:121.PubMedGoogle Scholar
  43. Szabo, S., and Pfeiffer, C.J. (eds.), 1989, “Ulcer Disease: New Aspects of Pathogenesis and Pharmacology”, CRC Press, Boca Raton.Google Scholar
  44. Szolcsányi, J., Joo, F., and Jancsó-Gábor, A., 1971, Mitochondrial changes in preoptic neurons after capsaicin desensitization of the hypothalamic thermodetectors in rats. Nature 229:116.PubMedCrossRefGoogle Scholar
  45. Szolcsányi, J., Jancsó-Gábor, A., and Joo, F., 1975, Functional and fine structural characteristics of the sensory neuron blocking effect of capsaicin, Naunyn-Schmiedeberg’s Arch. Pharmacol. 287:157.CrossRefGoogle Scholar
  46. Szolcsányi, J., and Barthó, L., 1981, Impaired defense mechanism to peptic ulcer in the capsaicin-desensitized rat, in: “Gastrointestinal Defense Mechanisms”, Vol. 29, Mózsik, G., Hanninen, O., and Jávor, T., eds., Pergamon Press, New York.Google Scholar
  47. Szolcsányi, J., and Mózsik, G., 1984, Effects of capsaicin on the development of gastric mucosal damage by different necrotizing agents and of gastric cytoprotection by PGI2, a-tropine and Cimetidine on rats, in: “Recent Advances in Gastrointestinal Cytoprotection”, Mözsik, G. and Bertelli, A., eds., Akadémiai Kiadó, Budapest.Google Scholar
  48. Tarnawski, A., and Hollander, D., 1989, Sucralfate protection of the gastric mucosa against ethanol injury, Chpt. 26 in: “Ulcer Disease: New Aspects of Pathogenesis and Pharmacology”, Szabo, S., and Pfeiffer, C.J., eds., CRC Press, Boca Raton.Google Scholar

Copyright information

© Springer Science+Business Media New York 1991

Authors and Affiliations

  • Carl J. Pfeiffer
    • 1
  • Stefano Evangelista
    • 2
  1. 1.Department of Biomedical Sciences Virginia-Maryland Regional College of Veterinary MedicineVirginia Polytechnic Institute and State UniversityBlacksburgUSA
  2. 2.A. Menarini PharmaceuticalsPharmacology DepartmentFlorenceItaly

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