Elsevier

Autonomic Neuroscience

Volume 133, Issue 1, 30 April 2007, Pages 19-34
Autonomic Neuroscience

Review
Autonomic pathways regulating pancreatic exocrine secretion

https://doi.org/10.1016/j.autneu.2006.10.001Get rights and content

Abstract

The parasympathetic (PNS) and sympathetic (SNS) and nervous systems densely innervate the exocrine pancreas. Efferent PNS pathways, consisting of central dorsal motor nucleus of the vagus (DMV) and peripheral pancreatic neurons, stimulate exocrine secretion. The DMV integrates cortical (olfactory, gustatory) and gastric, and intestinal vagal afferent input to determine central PNS outflow during cephalic, gastric and intestinal phases of exocrine secretion. Pancreatic neurons integrate DMV input with peripheral enteric, sympathetic, and, possibly, afferent axon reflexes to determine final PNS input to all exocrine effectors. Gut and islet hormones appear to modulate both central and peripheral PNS pathways.

Preganglionic sympathetic neurons in the intermediolateral (IML) column of the spinal cord receive inputs from brain centers, some shared with the PNS, and innervate postganglionic neurons, mainly in prevertebral ganglia. Sympathetic innervation of the exocrine pancreas is primarily indirect, and inhibits secretion by decreasing blood flow and inhibiting transmission in pancreatic ganglia. Interactions between SNS and PNS pathways appear to occur in brain, spinal cord, pancreatic and prevertebral ganglia, and at neuroeffector synapses.

Thus, the PNS and SNS pathways regulating the exocrine pancreas are directly or indirectly antagonistic at multiple sites: the state of exocrine secretion reflects the balance of these influences. Despite over a century of study, much remains to be understood about the connections of specific neurons forming pancreatic pathways, their processes of neurotransmission, and how disruption of these pathways contributes to pancreatic disease.

Introduction

Autonomic innervation of the pancreas has been studied for over a century but its critical role in regulating exocrine secretion has only recently begun to be fully appreciated. Much of the early work established the effects of electrical stimulation or surgical and chemical disruption of large, mixed nerve trunks on secretion in vivo or in isolated, perfused organs. A plethora of potential neurotransmitters were also identified, although few were broadly and convincingly implicated exocrine secretion. Numerous recent reviews of the subject provide excellent detailed summaries of these earlier studies (Holst, 1993, Singer, 1993, Solomon, 1994, Owyang, 1996, Niebergall-Roth and Singer, 2001, Owyang and Williams, 2003). This review will focus rather on work, primarily from the last 20 years, defining the histology, neurochemistry, physiology, and pharmacology of pancreas-specific pathways; beginning in the CNS and ending at the neuroeffector synapses on acinar and duct epithelium and smooth muscle cells, and the microvasculature.

Section snippets

Vagal afferent neurons

Pancreatic vagal afferent neurons originate bilaterally in the nodose ganglia with the left and right ganglia predominantly innervating the duodenal and splenic lobes of the pancreas, respectively. Most of these small diameter (20 μ), capsaicin-sensitive sensory neurons contain substance P (SP) and/or calcitonin-gene related peptide (CGRP; Sharkey and Williams, 1983, Sharkey et al., 1984, Carobi, 1987, Rinaman and Miselis, 1987, Won et al., 1998). Anterograde tracing of nodose neurons labels

Pancreatic spinal afferent nerves

The pancreas receives spinal afferent innervation originating in T6-L2 (DRG), and traversing the splanchnic nerves and celiac plexus, before entering the pancreas mixed with postganglionic sympathetic nerves. Most of these capsaicin-sensitive, DRG neurons contain substance P (SP) and/or CGRP (Sharkey and Williams, 1983, Sharkey et al., 1984, Rinaman and Miselis, 1987, Won et al., 1998). Spinal afferents transmit both mechanoreceptive and nociceptive information to the preganglionic sympathetic

Innervation and neural regulation of acinar cells

Vagotomy or sympathectomy has little effect on acinar cell innervation, indicating it is primarily supplied by pancreatic neurons (Richins, 1945, Radke and Stach, 1986a, Radke and Stach, 1986b). Varicose nerve bundles in the interacinar spaces, often traveling with capillaries, supply fibers that pass over the surface of acinar cells with multiple varicosities (1–8) contacting single cells (Richins, 1945). Nerve terminals supplying acinar cells at the boundary with islets of Langerhans also

Conclusions

Multiple autonomic reflexes, central and peripheral, parasympathetic and sympathetic, monitor the contractile and luminal state of the GI tract, and blood glucose levels during digestion. These reflexes converge on, and are integrated with the intrinsic activity of, key populations of pre-and post-ganglionic efferent neurons that determine the final parasympathetic and sympathetic outflow to the pancreas. These reflexes appear to be tonically active, interactive, and, predominantly

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