Spatial and temporal dynamics of innervation during the development of fetal human pancreas

The delineation of pancreatic nerve innervation during fetal life may contribute to our understanding of pancreatic pain modalities after birth. The aim of this study was to characterize the spatial and temporal distribution of nerve structures in the human pancreas throughout gestation. Computer-based image morphometry with piecewise polynomial interpolation analysis was performed to quantify nervous structures in the head, body and tail of the pancreas. Nerve structures were detected by automatic immunostaining techniques using a polyclonal antibody against two S-100 proteins that reacts strongly with human S100A and B that are detected in Schwann cells. Immunoreactivity was found in the parenchyma of head, body and tail of the pancreas with the relative density being head>body>tail. In addition to this extensive set of nerve fibers terminating in the pancreas there were large bundles of en passant nerve fibers in the dorsal region of the pancreas that were 3D reconstructed and were associated with the superior mesenteric plexus. If at first glance, the perimeter and the width of the nerve fibers seem to increase at a continuous rate up to term in all three regions of the pancreas, spatial and temporal co-analysis identified that the head of the pancreas shows a two-peak growth increase at 14 and 22 weeks of gestation with regard to the area, perimeter and width of the nerve structures, while the body and tail regions show a unique peak at 20 weeks. A developmental deceleration was found between the 22nd and the 36th week of gestation for the head region only. This is the first systematic study of nerve innervation of the human pancreas throughout gestation. The developmental dynamics of the pancreas nerve innervation corresponds approximately to the remodeling of the intrahepatic biliary system. Understanding the factors and disease states that may alter the distribution of nerve structures can be of significance for the development of therapies in pancreatic disorders of child- and adulthood.