What is the nerve supply of the pancreas?

Pancreatic Nerve Supply

Overview of Innervation

The pancreas receives dual autonomic innervation from both parasympathetic (vagal-cholinergic) and sympathetic (adrenergic) nervous systems, with parasympathetic fibers primarily stimulating secretion while sympathetic fibers inhibit it. 1

Parasympathetic (Vagal) Innervation

Central and Peripheral Components

• The parasympathetic pathway consists of central neurons in the dorsal motor nucleus of the vagus (DMV) and peripheral pancreatic ganglia that integrate signals to regulate exocrine secretion. 2
• The DMV integrates cortical input (olfactory, gustatory) and gastric/intestinal vagal afferent signals to determine parasympathetic outflow during cephalic, gastric, and intestinal phases of secretion. 2

Neurotransmitters and Function

• Parasympathetic nerves utilize acetylcholine as the primary neurotransmitter, identified by vesicular acetylcholine transporter (VAChT) expression. 3
• VAChT-positive parasympathetic nerve fibers are located at peri-acinar and perivascular spaces, following blood vessels to reach the islets. 3
• Neuropeptides including vasoactive intestinal polypeptide (VIP), pituitary adenylate cyclase activating polypeptide (PACAP), and gastrin-releasing peptide are also constituents of parasympathetic terminals. 4

Physiological Role

• Vagally-mediated cephalic phase contributes up to 40% of the overall pancreatic secretory response. 1
• Parasympathetic stimulation enhances insulin secretion from beta cells and stimulates exocrine enzyme output. 4, 5
• The parasympathetic system mediates the cephalic phase of insulin secretion and synchronizes islets to function as a unit, allowing oscillations of hormone secretion. 4

Sympathetic (Adrenergic) Innervation

Anatomical Pathway

• Preganglionic sympathetic neurons originate in the intermediolateral (IML) column of the spinal cord and synapse primarily in prevertebral ganglia (celiac and superior mesenteric ganglia). 2
• The pancreas receives sympathetic supply mainly through the greater and lesser splanchnic nerves. 6

Neurotransmitters and Distribution

• Sympathetic fibers are identified by tyrosine hydroxylase (TH) expression, indicating noradrenergic transmission. 3
• TH-positive sympathetic nerves are found at peri-acinar and perivascular spaces, similar to parasympathetic distribution. 3
• Neuropeptides galanin and neuropeptide Y are localized to sympathetic nerve terminals. 4

Mechanism of Action

• Sympathetic innervation primarily inhibits secretion indirectly by decreasing pancreatic blood flow and inhibiting transmission in pancreatic ganglia. 2
• Sympathetic activation inhibits insulin secretion from beta cells, particularly during stress-induced states. 4, 5
• The sympathoadrenal system is activated during metabolic stress (hemorrhagic hypotension, hypoglycemia), resulting in increased glucagon secretion. 6

Sensory (Afferent) Innervation

Anatomical Distribution

• Substance P (SP)-positive sensory afferent nerves reside along the basal domain of interlobular ducts. 3
• Calcitonin gene-related peptide (CGRP) is localized to sensory nerve terminals. 4

Unique Features in Humans

• Unlike mouse pancreas, human pancreas lacks SP-positive afferent nerves within the islets themselves. 3
• Hepatic glucoreceptors are postulated to be coupled with capsaicin-sensitive afferent nerves, conveying sensory signals of blood glucose concentration to the central nervous system. 6

Intrapancreatic Ganglia

Cellular Composition

• In intrapancreatic ganglia, SP-positive neurons (scattered minority, ~7%) co-localize with VAChT-positive neurons, suggesting local afferent-efferent interaction. 3
• Pancreatic neurons integrate DMV input with peripheral enteric, sympathetic, and possibly afferent axon reflexes to determine final parasympathetic input to exocrine effectors. 2

Functional Significance

• Human pancreas has lower ganglionic density compared to mouse pancreas. 3
• These ganglia serve as integration centers where interactions between sympathetic and parasympathetic pathways occur. 2

Neural Regulation of Secretion

Integrated Control Mechanisms

• Postprandial pancreatic secretion is mediated by vagal-cholinergic reflexes and cholecystokinin (CCK), with tight interaction between neural and humoral systems. 1
• CCK acts both as a stimulatory neuromodulator of the cholinergic pathway and as a hormone. 1

Antagonistic Balance

• The state of exocrine secretion reflects the balance between parasympathetic stimulation and sympathetic inhibition, with interactions occurring at multiple sites: brain, spinal cord, pancreatic and prevertebral ganglia, and neuroeffector synapses. 2

Clinical Relevance

Pain Pathways

• Pancreatic cancer pain often has neuropathic components due to tumor proximity to the celiac axis, which contains the sympathetic nerve supply. 7
• Celiac plexus block targets the sympathetic innervation for pain management in pancreatic cancer. 8, 9

Adipose Innervation

• Human pancreas shows obvious presence of VAChT-positive and TH-positive nerves around intralobular adipocytes, implicating neural influence on pancreatic steatosis. 3

Important Caveats

• The autonomic nervous system influences pancreatic regeneration and may stimulate carcinogenesis, though mechanisms remain incompletely understood. 5
• Despite over a century of study, much remains unknown about specific neuronal connections, neurotransmission processes, and how pathway disruption contributes to pancreatic disease. 2