Definition and Overview
Autonomic ganglia is a nerve relay structure where autonomic nerve fibers (preganglionic nerve fibers) from the central nervous system form synapses with peripheral nerve cells (postganglionic nerve cells). The motor path of the autonomic nervous system must pass through two nerve cells to reach the target organ, and the place where the alternation takes place is the autonomic ganglion.
The autonomic ganglion is not just a signal relay station. Inside the node, interneurons exist and perform the function of integrating and regulating signals. Signal amplification and precise control are achieved through a structure in which one preganglionic nerve fiber connects to multiple postganglionic neurons or multiple preganglionic nerves converge on one postganglionic neuron. Understanding the types of neurotransmitters and receptors used in autonomic ganglia is a key element in understanding the pathophysiology and drug treatment principles of autonomic diseases.
Structure of autonomic ganglion
sympathetic ganglion
Sympathetic preganglionic neurons are located in the intermediolateral column of the spinal cord between the 1st thoracic and 2nd lumbar vertebrae. The axons of these neurons exit through the anterior spinal cord and form synapses with postganglionic neurons in the sympathetic ganglion.
Sympathetic ganglia are divided into two types depending on their location.
- Paravertebral ganglia: Approximately 22 pairs of ganglia arranged in a chain along both sides of the spine. The upper, middle, and lower cervical ganglia and the thoracic, lumbar, and superficial ganglia constitute the sympathetic trunk. The inferior cervical ganglion at the bottom of the neck combines with the first thoracic ganglion to form the stellate ganglion, which is the main relay point for sympathetic nerves heading to the head, neck, and upper extremities.
- Prevertebral ganglia: Located in front of the abdominal aorta, these include the celiac ganglion, superior mesenteric ganglion, and inferior mesenteric ganglion. It relays sympathetic nerves to the abdominal and pelvic organs.
The sympathetic nerve has the structural characteristic of having short preganglionic nerve fibers and long postganglionic nerve fibers. This is because the ganglion is located close to the central nerve. One preganglionic neuron forms synapses with an average of 20 to 30 postganglionic neurons, so even a small number of central signals can cause a wide range of peripheral responses.
parasympathetic ganglion
Parasympathetic preganglionic neurons are located in the brain stem (midbrain, pons, medulla) and sacral cord (S2-S4). The parasympathetic nerves originating in the brain stem are directed to target organs through the 3rd (oculomotor), 7th (facial), 9th (glossopharyngeal), and 10th (vagus) cranial nerves.
Unlike sympathetic ganglia, parasympathetic ganglia are located right next to the target organ or inside the organ wall (intramural ganglia). For this reason, the preganglionic nerve fibers are long and the postganglionic nerve fibers are very short. Since one preganglionic neuron forms synapses with only a small number of postganglionic neurons, more local and precise control is possible compared to sympathetic neurons. The vagus nerve is responsible for approximately 75% of parasympathetic output and controls a wide range of internal organs, including the heart, lungs, and gastrointestinal tract.
neurotransmitter
Preganglionic nerve fibers: acetylcholine and nicotinic receptors.
The neurotransmitter of preganglionic nerve fibers in both the sympathetic and parasympathetic nerves is acetylcholine (ACh). Acetylcholine secreted from preganglionic nerve terminals binds to nicotinic acetylcholine receptor (nAChR) on the postganglionic nerve cell membrane, causing excitatory postsynaptic potentials.
Nicotine receptors in the autonomic ganglion are of a different subtype than nicotine receptors in the neuromuscular junction. The nAChRs in ganglia are mainly of the α3β4 subtype, which is distinct from the α1β1δε subtype in the neuromuscular junction. Differences between these subtypes determine differences in drug sensitivity.
Postganglionic nerve fibers: sympathetic nerves
The main neurotransmitter in sympathetic postganglionic nerve fibers is norepinephrine (NE). Norepinephrine exerts its effects by binding to adrenergic receptors in target organs. Adrenergic receptors are divided into two major categories, alpha (α) and beta (β), and each has subtypes (α1, α2, β1, β2, and β3).
The distribution and function of major adrenergic receptors are as follows.
- α1 receptor: distributed in vascular smooth muscle, when activated causes vasoconstriction and increase in blood pressure.
- α2 receptor: distributed in preganglionic nerve terminals and performs a negative feedback function to suppress norepinephrine secretion.
- β1 receptor: distributed in the heart, when activated causes an increase in heart rate (positive inotropic effect) and an increase in myocardial contractility (positive inotropic effect).
- β2 receptor: distributed in bronchial and vascular smooth muscles, when activated causes bronchodilation and vascular relaxation.
According to one study, a cotransmission phenomenon was confirmed in which sympathetic postganglionic nerves simultaneously secrete ATP and neuropeptide Y in addition to norepinephrine. These cotransmitters play a role in regulating or supplementing the effects of the main neurotransmitter.
Postganglionic nerve fibers: parasympathetic
The neurotransmitter of parasympathetic postganglionic nerve fibers is acetylcholine. Acetylcholine secreted from postganglionic nerve terminals binds to muscarinic acetylcholine receptor (mAChR) in target organs. There are five subtypes of muscarinic receptors, M1 to M5, and their distribution varies depending on the organ.
- M2 receptor: distributed in the heart, when activated causes a decrease in heart rate and atrioventricular conduction delay.
- M3 receptor: distributed in bronchial smooth muscle, gastrointestinal smooth muscle, and exocrine glands, and causes bronchoconstriction, stimulation of intestinal motility, and secretion of saliva and gastric acid.
In addition to acetylcholine, parasympathetic postganglionic neurons also secrete co-transmitters such as nitric oxide (NO) and vasoactive intestinal peptide (VIP).
Exceptional structures: sweat glands and adrenal medulla
There are two notable exceptions to the general principle of autonomic nerve transmission.
First, sympathetic postganglionic nerve fibers that innervate the eccrine sweat glands use acetylcholine, not norepinephrine, as a neurotransmitter. The receptors in sweat glands are muscarinic receptors. It is known that neurotransmitter switching to a cholinergic phenotype occurs during development.
Second, the adrenal medulla is a structure that embryologically corresponds to the sympathetic ganglion. chromaffin cells in the adrenal medulla are modified postganglionic neurons that secrete epinephrine (approximately 80%) and norepinephrine (approximately 20%) directly into the bloodstream upon stimulation by acetylcholine from preganglionic sympathetic nerves. This is distinguished from a typical postganglionic nerve in that it is an endocrine type of signal transmission rather than a nerve transmission.
Receptors and Pharmacology
Most autonomic drugs act on neurotransmitter receptors. Because the effects of drugs vary depending on the type and location of the receptor, receptor pharmacology is the core of autonomic nerve treatment.
The major autonomic receptors and related drugs are as follows.
- Nicotine receptors (autonomic ganglia): When ganglion blockers (e.g. trimetaphan) block these receptors, both sympathetic and parasympathetic nerve transmission are inhibited. In the past, it was used for emergency treatment of severe hypertension, but its use is currently limited due to side effects due to non-selectivity.
- Muscarinic receptors (parasympathetic postganglionic effectors): Atropine blocks muscarinic receptors to increase heart rate, suppress saliva and gastric acid secretion, and dilate pupils. It is used as an initial treatment drug in bradycardia emergencies.
- α-Adrenergic receptor: α1 agonist (phenylephrine) constricts blood vessels and is used to relieve nasal congestion and treat low blood pressure. α1 blockers (prazosin) treat high blood pressure by relaxing blood vessels.
- β-Adrenergic receptor: β1 blockers (atenolol, metoprolol) reduce heart rate and myocardial contractility and are used to treat hypertension, angina pectoris, and arrhythmia. β2 agonists (salbutamol) are used to treat asthma by dilating the bronchi.
Selectivity for receptor subtype is important when selecting a drug. Since non-selective beta blockers (propranolol) block both β1 and β2 and can cause bronchoconstriction, β1-selective blockers are used in asthma patients.
Clinical significance
Points of action of autonomic drugs
Many drugs commonly used in daily life act on autonomic ganglia and neurotransmitter receptors. Beta blockers, used to treat high blood pressure, are one of the most commonly prescribed drugs worldwide. They are reported to have the effect of reducing heart rate by about 10 to 15 beats per minute by selectively blocking the heart's β1 receptors. Studies have shown that salbutamol, a bronchodilator, selectively acts on β2 receptors and improves forced expiratory volume in 1 second (FEV1) in asthma patients by 15-30%.
Autoimmune autonomic ganglionopathy
Autoimmune autonomic ganglionopathy (AAG) is a disease in which preganglionic to postganglionic nerve transmission is blocked due to the formation of autoantibodies against nicotinic receptors (α3 subtype) in autonomic ganglia. In a study by Vernino et al. in 2000, anti-ganglionic nicotinic receptor antibodies (ganglionic AChR antibodies) were detected in approximately 50% of patients with autonomic dysfunction, and a significant correlation was confirmed between antibody titers and the severity of autonomic dysfunction.
The main symptoms of AAG are orthostatic hypotension, gastroparesis, pupil abnormalities (anisocoria), decreased sweating, dry mouth and eyes, and urination problems. For diagnosis, serum antiganglionic AChR antibody test and autonomic function tests (heart rate variability analysis, tilt-table test, sweating function test) are used.
Treatment includes immunotherapy such as intravenous immunoglobulin therapy, plasmapheresis, and immunosuppressants, and significant improvement in symptoms has been reported in some patients.
life management
Lifestyle rules to maintain healthy autonomic ganglia and neurotransmitter functions are as follows.
- Regular aerobic exercise: Walking, swimming, or cycling for more than 30 minutes, 3 to 5 times a week, helps restore autonomic balance. Exercise has been reported to improve heart rate variability by increasing parasympathetic nerve activity.
- Sufficient sleep: Regular sleep of 7 to 8 hours is essential for the recovery of the autonomic nervous system. During sleep, the parasympathetic nervous system becomes dominant, lowering heart rate and promoting tissue recovery.
- Stress management: Chronic stress causes autonomic imbalance by continuously increasing norepinephrine secretion from sympathetic postganglionic nerves. Relaxation training such as abdominal breathing and meditation helps suppress sympathetic nerve overactivity.
- Balanced diet: Excessive caffeine stimulates the sympathetic nervous system, and alcohol dulls the autonomic reflexes. Sufficient water and electrolyte intake is important for controlling blood pressure.
- Caution when taking drugs: Drugs that act on autonomic nerve receptors must be taken according to a specialist's prescription. If you stop or change the dose arbitrarily, a rebound effect may occur.
If symptoms of autonomic abnormality persist, objective evaluation through heart rate variability testing and consultation with a specialist are recommended.