Abstract
The existence of chronic appendicitis is controversial. In this prospective study, we investigated possible changes in the innervation of the appendix under different pathological conditions and correlated histological findings with clinical observation. Thirty appendectomy specimens and 14 appendices obtained from organ donors or patients who underwent right hemicolectomy were immediately fixed in Bouin's solution and processed for immunocytochemistry using an antiserum directed against the panneuronal marker protein gene product 9.5 (PGP 9.5). The density of PGP 9.5 immunostaining was evaluated by digitized morphometry. Significant differences in the density of the PGP 9.5-immunoreactive area were detected in the mucosal layer. In the nonacute appendicitis group, PGP 9.5 was increased (10.99±3.15%) as compared to acute appendicitis (3.89±1.77%) and controls (4.98±1.25%). The significant increase of PGP 9.5 in nonacute appendicitis may suggest axonal sprouting leading to hyperinnervation of the mucosa. This may be a neuronal factor in the pathophysiology of the disease and pain symptoms.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Shaw PAV: The innervation and neuroendocrine cell population of the appendix in total colonic aganglionosis. Histopathology 17:117–121, 1990
Masson P: Neuronal proliferation in the vermiform appendix.In Cytology of the Nervous System, Vol. III. W Penfield (ed). 1932, pp 1095–1130
Auböck L, Ratzenhofer M: Extraepithelial enterochromaffin cell-nerve fibers complexes in the normal human appendix and in neurogenic appendicopathy. J Pathol 136:217–226, 1982
Sjölund K, Schaffalitzky De, Muckadell OB, Fahrenkrug J, Håkanson R, Peterson BG, Sundler F: Peptide containing-nerve fibers in the gut wall in Crohn's disease. Gut 24:724–733, 1983
O'Morain C, Bishop AE, McGregor GP, Levi AJ, Bloom SR, Polak JM, Peters TJ: Vasoactive intestinal polypeptide concentrations and immunohistochemical studies in rectal biopsies from patients with inflammatory bowel disease. Gut 25:57–61, 1984
Weihe E, Nohr D, Müller S, Büchler M, Friess H, Zentel HJ: The tachykinin neuroimmune connection in inflammatory pain. Ann NY Acad Sci 632:283–295, 1991
Büchler M, Weihe E, Friess H, Malfertheiner P, Bockmann DE, Müller S, Nohr D, Beger HG: Changes in peptidergic innervation in chronic pancreatitis. Pancreas 7:183–192, 1992
Shelley HJ: Chronic appendicitis, is it a clinical entity? Arch Surg 37:17–45, 1938
Gullino P, Calderola L: Nuovo in istologia per la diagnosi di appendicite cronica. Minerva Med 1:592–597, 1952
Schreiber HW, Otto HF, Koch G, Kortmann KB: Chirurgische Krankeiten der Appendix vermiformis. Chirurg 49:679–683, 1978
Lau WY, Fan ST, Yiu TF, Chu KW, Suen HC, Wong KK: The clinical significance of routine histopathologic study of the resected appendix and safety of appendiceal inversion. Surg Gynecol Obstet 162:256–258, 1986
Brooks SG, Huges RG: Selective histopathology of appendicectomy specimens. Lancet 2:1456, 1987 (letter)
Segal GH, Petras RE: Vermiform appendix.In Histology for Pathologists. SS Sternberg (ed). New York, Raven Press, 1992, pp 593–605
Zentel HJ, Weihe E: The neuro-B cell link of peptidergic innervation in the bursa Fabricii. Brain Behav Immun 5:132–147, 1991
Ekblad E, Arnbjornsson E, Ekman R, Hakanson R, Sundler F: Neuropeptides in the human appendix. Dig Dis Sci 34:1217–1230, 1989
Höfler H, Kasper M, Heitz Ph U: The neuroendocrine system of normal human appendix, ileum and colon, and in neurogenic appendicopathy. Virchows Arch A Pathol Anat Histopathol 399:127–140, 1983
Stead RH, Franks AJ, Goldsmith CH, Bienenstock J, Dixon MF: Mast cells, nerves and fibrosis in the appendix: A morphological assessment. J Pathol 161:209–219, 1990
Lundberg JM, Alm P, Wharton J, Polak JM: Protein gene product 9.5 (PGP 9.5). A new neuronal marker visualizing the whole uterine innervation and pregnancy-induced and developmental changes in the guinea pig. Histochemistry 90:9–17, 1988
Weihe E, Krekel J: The neuroimmune connection in the human tonsils. Brain Behav Immun 5:41–54, 1991
Olsen BS, Holck S: Neurogenous hyperplasia leading to appendiceal obliteration: an immunohistochemical study of 237 cases. Histopathology 11:843–849, 1987
Weihe E, Nohr D, Millan MJ, Stein C, Müller S, Gramsch C, Herz A: Peptide neuroanatomy of adjuvant-induced arthritic inflammation in rat. Agents Actions 25:255–259, 1988
Weihe E: Neurochemical anatomy of the mammalian spinal cord: Functional implications. Ann Anat 174:89–118, 1992
Aloe L, Tuveri MA, Levi-Montalcini R: Studies on carrageenan-induced arthritis in adult rats: Presence of nerve growth factor and role of sympathetic innervation. Rheumatol Int 12:213–216, 1992
Weihe E, Nohr D, Michel S, Müller S, Zentel HJ, Fink T, Krekel J: Molecular anatomy of the neuro-immune connection. Int J Neurosci 59:1–23, 1991
Author information
Authors and Affiliations
Additional information
P. Di Sebastiano is a recipient of a grant of the Italian Minister for University and Research and G. D'Annunzio University of Chieti, Italy.
This work was supported by the German Minister for Research and Technology (BMFT grant 07 0118/7 to M.B. and E.W.) and a grant of Stiftung Volkswagenwerk (to EW).
Rights and permissions
About this article
Cite this article
di Sebastiano, P., Fink, T., Weihe, E. et al. Changes of protein gene product 9.5 (PGP 9.5) immunoreactive nerves in inflamed appendix. Digest Dis Sci 40, 366–372 (1995). https://doi.org/10.1007/BF02065423
Received:
Revised:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF02065423