Innervation and Secretory Function of Transplanted Human Submandibular Salivary Glands

Abstract

Free submandibular gland autotransplantation is used to treat absolute tear deficiency. Although disconnected from any peripheral innervation, most transplants show increasing secretion for years. We have evaluated the secretory activity and autonomic innervation of such transplants. Secretory activity of glands in response to parasympatholytics and parasympathomimetics was evaluated by Schirmer's test and Technetium scintigraphy. Submandibular gland tissue specimens taken before and after transplantation were examined histologically. Relative hypersecretion during the first postoperative week suddenly decreased but then slowly increased during the first postoperative year. Hypersecretion was significantly reduced by parasympatholytics while carbachol rapidly increased secretion. Histology of transplanted glandular tissue showed parenchymal atrophy. Cholinesterase-positive nerves were abundant and in a similar distribution to normal with scattered positive ganglion cells. Adrenergic axons were fewer than normal and irregularly distributed. Early hypersecretion may be due to release of neurotransmitters from degenerating terminal axons. This is followed by a period of minimal secretion during which hypersensitivity of acinar cells develops. With spontaneous reinnervation, secretion is accentuated by external sympathetic vasomotor adrenergic drive. This shows that submandibular glands can remain viable despite complete separation from their normal nerve supply and are capable of regaining a substantial secretory activity for years.

Transplantation of the Major Salivary Glands

“…Over the subsequent months the amount of secretion increases. Contrary to short-term reports by others, after 1 year this can result in excessive salivary epiphora [4,20,26,30]. Although the secretory flow does not depend on gustatory stimuli, it is stimulated by physical activity, local hyperthermia or caffeine ingestion.…”

“…Adrenergic axons are also present in the glands but are less numerous than normal and more irregularly distributed. The latter are thought to have originated from sectioned sympathetic nerves around reconnecting arteries and to have grown by sprouting down mainly formerly parasympathetic glandular nerves [30].…”

The timing of acid-induced increase in saliva secretion in transplanted submandibular glands

“…16 This indicates that sympathetic activation affects the secretory activity of the transplanted SMG. Geerling et al 12 observed irregularly distributed adrenergic axons in the transplanted SMG. In addition to autonomic nerves, secretion-related receptors on the cell membrane, such as TRPV1, and tight junctions also play an important role in regulating secretion from normal and transplanted SMGs.…”

“…The hypersensitive mAChRs would then induce AQP5 trafficking out of lipid rafts, resulting in excessive gland secretion. 11 Geerling et al 12 demonstrated the distribution of autonomic nerve endings in transplanted SMGs in the long term. These fundamental research studies indicate the possibility of reinnervation of the transplanted glands.…”

Immunohistochemical characterisation of neurons in the mandibular ganglion and nerve fibres supplying the porcine mandibular gland

“…Similarly distributed ganglia were also observed in the stroma of the human MGl (Geerling et al 2008;Tosios et al 2010). In humans, the small ganglia were observed to be in close association with salivary parenchymal cells and blood vessels.…”