Neural Control of the Gastrointestinal System

Abstract

In communication between the central nervous system (CNS), autonomic nervous system (ANS), and the enteric nervous system (ENS), sensory afferent fibers relay information pertaining to varying conditions, while efferent fibers stimulate effectors to modulate functions such as secretion and motility. Local feedback loops regulated by the ENS and long loops involving the CNS facilitate fine tuning of gastrointestinal function.

Keywords

Autonomic nervous system, Central nervous system, Enteric nervous system, Gastrointestinal tract, Peripheral nervous system

Outline
Introduction 1373
Central Nervous System Control 1373
Extrinsic Control by the Autonomic Nervous System 1374
Intrinsic Gastrointestinal Control Though the Enteric Nervous System 1375
Gastrointestinal Reflexes 1376
Conclusion 1377
References 1378
Further Reading 1378

Introduction

Motility and secretion are controlled through neural, hormonal, and paracrine systems. The hierarchy of neural control begins in the enteric nervous system (ENS), a localized intrinsic system able to self-regulate control. Modification and regulation of gastrointestinal (GI) function also occurs with help of higher brain centers within the central nervous system (CNS), and the autonomic nervous system (ANS), which is comprised of sympathetic and parasympathetic branches. The sympathetic nervous system predominantly provides inhibitory feedback slowing gastric motility, decreasing mucosal secretion, and diverting blood supply away from GI tract. The parasympathetic nervous system largely functions as the opposite of the sympathetic nervous system and generally stimulates the GI tract. Neural centers are regulated by one another through sensory feedback pathways, which travel in autonomic nerves. The full circuit creates feedback loops forming reflexes regulated by the CNS or ENS. Gastric function is often presumed to be an unconscious process but higher brain centers in the CNS are influenced by emotion and cognition and can alter function. This chapter will focus on the anatomy, and physiology associated with the neural pathways, which control the GI system.

Central Nervous System Control

Although gastric function is able to operate through enteric mechanisms, extrinsic input from the CNS is essential to maintain organized digestion. Higher command centers in the brain initiate vagal efferent, descending pathways in the spinal cord, which connect to preganglionic neurons in the thoracolumbar and sacral regions. Studies using retrograde transneuronal viruses have identified GI neurological involvement in the nucleus tractus solitaries (NTS), parabrachial complex, hypothalamus, amygdala, area postrema, and periaquadectal gray matter ( ). These locations alter efferent signals by receiving sensory information originating from parasympathetic, and sympathetic afferents from the viscera. The conglomeration of sensory information from throughout the GI tract helps modify outflow signals to particular regions.

The NTS acts as the only CNS input center for both parasympathetic and sympathetic sensory information. Spinal sensory input within the NTS facilitates communication with other CNS nuclei, altering control of efferent signaling to the GI tract ( ). Visceral afferent signals are relayed to the CNS via parasympathetic vagal afferents while nociceptive stimulation from the GI system are relayed by sympathetic, spinal, afferent signals. The visceral afferents are thought to carry physiologic information like distention, motility, satiety, and nausea. The convergence of sympathetic and parasympathetic afferents to the NTS facilitates efferent information, influencing output from both ANSs ( ).

Mechanisms of signaling from specific CNS centers to other centers is largely unknown. As some CNS centers in the brainstem remain outside of the blood-brain barrier, it is proposed that accessibility to various hormones, cytokines, and neuromodulators plays a role in GI modulation ( ). Regions such as the frontal cerebral cortex, stria terminalis, parabrachial complex, hypothalamus, amygdala, and periaqueductal gray matter have projections to vagal output centers in the medulla oblongata ( ). These regions have pathways within the limbic region of the brain, which is known to process emotional responses. These connections may explain how cognitive changes such as stress, change in sleep patterns, depression, and emotional events may induce GI symptoms such as nausea, diarrhea, decreased food intake, abdominal pain, and emesis ( ).

The understanding of how CNS pathways maintain homeostasis within the GI tract is incompletely understood. Further understanding requires analysis of neurological and hormonal changes that are related to physiological phenomena within the GI system. The association of cognition and emotion with functional GI disorders provides opportunity for novel therapeutic interventions.

Extrinsic Control by the Autonomic Nervous System

ANS regulation of the GI tract occurs though direct stimulation of smooth muscle and secretory cells and indirectly through influence on the ENS. The ANS is divided into sympathetic and parasympathetic components. Both components function to relay sensory information to the CNS though afferent signaling, as well as efferent components to the GI tract. Traditionally, the parasympathetic division controls normal physiological gut functions such as motility and digestion, primarily through vagal efferent stimulation. Sympathetic fibers cause the opposite effects by limiting motility, vasoconstricting blood supply, and decreasing digestive capabilities.

Parasympathetic preganglionic neurons arise from cranial nerve X (the vagus nerve), originating in the brainstem as well as within the spinal cord at vertebral levels S2 to S4 ( ). These neurons consist of two components, afferents sending sensory information to the CNS and efferents sending signals back to the organs. Vagus fibers innervate the esophagus, stomach, pancreas, small intestine, liver, ascending colon, and transverse colon. Sacral parasympathetic nerves innervate the descending colon. The vagus nerve has left and right components. The left branch forms the celiac and left gastric nerve. The right branch forms the hepatic, right gastric, and accessory celiac nerves. Physiological effects of the vagus were noted in early clinical trials with the use of vagotomy for treatment for peptic ulcer disease ( ). Parasympathetic modulation occurs through direct stimulation of smooth muscle fibers and stimulation of secretory cells directly, but also indirectly through synapses with neurons of the Myenteric and submucosal plexus’ of the ENS.

Sympathetic preganglionic nerves arise in the dorsal root ganglia of T1-L2 regions of the thoracic and lumbar spinal cord. These preganglionic nerves travel and synapse with paravertebral sympathetic ganglia known as the celiac, superior mesenteric, and the inferior mesenteric ganglions. Prevertebral, synaptic, sympathetic transmission occurs through acetylcholine (ACh) acting on nicotinic receptors and via norepinephrine (NE) acting on adrenergic receptors at effector cells and the neurons of the ENS. The postganglionic neurons travel with blood vessels to the GI system and innervate the ENS as well as peripheral target tissues directly. Sympathetic fibers have inhibitory effects on the GI tract via parasympathetic fibers, which inhibits motility, secretion, splanchnic blood flow, and sphincter dilation.

Traditionally ANS input to the ENS was thought to be though direct stimulation of enteric nervous fibers, which would in turn stimulate effectors in the GI tract for actions on musculature, secretory, and sensory cells. More recent literature suggests the ENS is able to self-regulate and process information ( ). The ANS is able to modulate the ENS though excitatory (ACh via the parasympathetic) and inhibitory (NE via the sympathetic) neurotransmitters on the interneurons of the ENS as well as directly to the effectors ( Fig. 114.1 ).