Background: Current conflicting information on the innervation of the
human oral cavity indicates technical problems such as different detec
tability of the neural structures according to the various staining me
thods used and difficulties in reproducibility. The possibility of int
raoral regional differences has not been properly considered. Methods:
Human biopsies of mucosa from different intraoral regions were prepar
ed for immunohistochemistry using protein gene product 9.5 (PGP 9.5; a
marker for neuronal structures). Results: Nerves were found consisten
tly in all the biopsies. The neural pattern showed clear regional diff
erences. Intraepithelial nerve fibers were found in the gingiva, labia
, palate, within certain fungiform papillae, and in some salivary excr
etory ducts. Organized nerve endings were found in varying frequencies
in all but one (sublingual) region, appearing as lamellar (Meissner-l
ike), coiled or glomerular neural structures, Merkel cell-neurite comp
lexes were observed in the buccal, gingival, and palatal epithelia. Im
munoreactive cells with many similarities to Merkel cells but without
a neural connection were also encountered. Conclusions: Conflicting re
sults from earlier innervation studies of the oral cavity could be att
ributed to regional innervation differences. The distribution of the n
erves also casts doubt on some of the present theories concerning the
function(s) of intraoral nerves, such as the free nerve endings and th
e Merkel cell-neurite complexes. (C) 1996 Wiley-Liss, Inc.