Where do most parasympathetic ganglia reside?

Parasympathetic Ganglia

Parasympathetic ganglia in general are smaller than sympathetic ganglia and lie closer to or within their target organs. Within the head, the ciliary ganglia supply the iris and ciliary muscles, the sphenopalatine ganglia supply blood vessels and glands of the hair follicles of facial skin, the submandibular ganglia supply the submandibular salivary glands, and the otic ganglia supply the parotid glands. Parasympathetic ganglia are also associated with the respiratory tract, heart (see Chapter 10), accessory digestive organs such as the pancreas and gallbladder, sigmoid colon, urinary bladder, and reproductive organs. Two “parasympathetic” ganglia are classified separately. The pelvic ganglia are often considered parasympathetic but they are mixed parasympathetic-sympathetic ganglia (see Chapter 14). They can vary in structure from a single large ganglion in some species to a meshwork or plexus at the junction of the hypogastric and pelvic nerves to ganglia dispersed over the surface of some pelvic organs. The enteric division of the autonomic nervous system, once considered to be terminal parasympathetic ganglia, is discussed elsewhere in this text (see Chapter 12).

Location of Autonomic Ganglia

Parasympathetic ganglia which innervate targets in the head are located in four main ganglia: the ciliary, pterygopalatine, submandibular and otic ganglia. Scattered microganglia may also be distributed along cranial nerves. Parasympathetic ganglia innervating the airways, heart, and pancreas are located close to, or within the organs. Parasympathetic neurons innervating the pelvic viscera are largely located in pelvic ganglia. In males, these consist of the main pelvic ganglia and one or two accessory ganglia (Rogers et al., 1990; Wanigasekara et al., 2003; 2004). In females, pelvic ganglia are termed paracervical ganglia – indicating their location near the uterine cervix junction (Jobling and Lim, 2008). In both female and male mice, the arrangement of the pelvic plexus is less complex than in many mammals (Jobling et al., 2003; Keast, 1999). Pelvic ganglia are unusual anatomically, as they house final motor neurons in sympathetic and parasympathetic ganglia (Jobling and Lim, 2008; Wanigasekara et al., 2003). Sympathetic ganglia are located in the paravertebral chain or in the prevertebral ganglia; which are collections of ganglia situated along the midline immediately ventral to the aorta near the branch points of the coeliac and mesenteric arteries.

Tracheal Ganglia

Parasympathetic ganglia from trachea were initially isolated from young rats, but cultures from mature guinea pigs and adult human organ donors have been isolated and maintained in cell culture for several weeks (see reports from laboratories of Professors Burnstock and Fryer). Tracheal ganglia behave similarly to nerves in vivo as they release acetylcholine, express nitric oxide synthase, and, depending upon the presence of NGF, express substance P. M2 muscarinic receptors are evenly distributed along on cell bodies and neurites and function to inhibit acetylcholine release. Similar to nerves in vivo, inflammatory cells adhere to parasympathetic nerves in culture, and this effect is regulated by expression of chemotactic cytokines and adhesion molecules by the parasympathetic nerves. Parasympathetic nerves also release some noradrenaline and have functional α1 adrenoceptors and γ-aminobutyric acid (GABAA) receptors. As with cardiac nerves, cultured ganglia from the trachea appear to maintain all characteristics of their in vivo counterparts.

Tracheal Parasympathetic Ganglia

Parasympathetic ganglia from trachea were initially isolated from young rats, but cultures from mature guinea pigs and adult human organ donors have been isolated and maintained in cell culture for several weeks (see papers from laboratories of Professors Burnstock and Fryer, listed in “Further reading”). Tracheal ganglia behave similarly to parasympathetic nerves in vivo as they release acetylcholine, express nitric oxide synthase and, depending upon the presence of NGF, express substance P. M2 muscarinic receptors are evenly distributed along cell bodies and neurites, and function to inhibit acetylcholine release. Similar to nerves in vivo, inflammatory cells adhere to parasympathetic nerves in culture, and this effect is regulated by expression of chemotactic cytokines and adhesion molecules by the parasympathetic nerves. Parasympathetic nerves also release some noradrenaline, and have functional M1 muscarinic, alpha1 adrenergic and GABAA receptors. As with cardiac nerves, ganglia cultured from the trachea appear to maintain all characteristics of their in vivo counterparts.

Ganglionic

Preganglionic nerves innervating the parasympathetic ganglia in the airways evoke action potentials during normal breathing with relatively high frequencies, in the range of 1–20 Hz. As a result, basal airway smooth muscle tone in vivo is mediated to a significant extent by cholinergic nerve activity. The pattern of ganglionic action potential bursts coincides with respiration, suggesting that the respiratory centers in the brainstem govern preganglionic nerve activity. However, in addition to this central drive, reflex stimulation through mechanically sensitive afferent nerve terminals in the lungs during respiration is importantly involved as well. The fidelity by which preganglionic impulses are translated into action potentials in the postganglionic neurons is relatively low in parasympathetic airway ganglia, implying a filtering function of these ganglia. This filtering function can be diminished by various inflammatory mediators. Thus, histamine, prostaglandin D2 (PGD2), and bradykinin are able to enhance ganglionic cholinergic transmission and the same is true for tachykinins (substance P, neurokinin A) released by nonmyelinated sensory C-fibers in the airways.

Superior and Inferior Salivatory Nuclei

The preganglionic fibers that innervate the major parasympathetic ganglia of the head arise in the superior and inferior salivatory nuclei. The preganglionic fibers that innervate the pterygopalatine and submandibular ganglia arise in the superior salivatory nucleus, and travel in the facial nerve (Mackay et al., 1997). It has been shown that the superior salivatory neurons arise in rhombomere 5 (r5), whereas the neurons of the main facial nucleus arise in r4 and migrate to r6 (Mackay et al., 1997). The cells of the superior salivatory nucleus in the mouse are closely applied to the emerging fibers of the facial nerve.

The inferior salivatory nucleus is an elongated cylindrical cell group that extends rostrally from the rostral pole of the vagal motor nucleus, along the medial margin of the solitary nucleus (Franklin and Paxinos, 2008). It ends just caudal to the rostral pole of the solitary nucleus. The inferior salivatory nucleus sends preganglionic fibers to the otic ganglion, which in turn supplies the parotid gland with secretomotor fibers. The fibers that arise in the inferior salivatory nucleus travel in the glossopharyngeal nerve.

Pterygopalatine Ganglion

The PPG is the largest of the peripheral parasympathetic ganglia. It is formed by the cell bodies of postganglionic parasympathetic neurons and resides in the PPF just below the maxillary nerve to which it connects by short ganglionic branches. It is located anterior to the pterygoid canal and lateral to the sphenopalatine foramen. This is an important ganglion that receives three roots: sensory, parasympathetic, and sympathetic. The sensory root is derived from the maxillary nerve and conveys the majority of sensory fibers of this nerve via the ganglionic branches (Standring, 2008). These sensory nerves pass through the ganglion without synapsing and are distributed in the nerves leaving the ganglion. The parasympathetic root is derived from the greater petrosal nerve via the pterygoid canal and consists of preganglionic parasympathetic fibers from the facial nerve, which synapse within the ganglion. Postganglionic parasympathetic fibers enter the maxillary nerve through its ganglionic branches for distribution to the lacrimal gland and to nerves leaving the ganglion to palatine and nasal mucous glands (Piagkou et al., 2011). Finally, the ganglion receives the sympathetic root as postganglionic sympathetic fibers that arise from the superior cervical ganglion and travel by way of the deep petrosal nerve and nerve of the pterygoid canal. They are distributed with the postganglionic parasympathetic fibers. Thus, each branch off the PPG contains sensory, postganglionic parasympathetic, and postganglionic sympathetic fibers.

Parasympathetic Division

As shown in Figure 2 and Table 1, parasympathetic ganglia are located close to or within the organs they innervate. Preganglionic fibers arise from the brain stem and sacral region of the spinal cord. The eye, face, and mouth are served by cranial verves III, VII, and IX. The cardiopulmonary and digestive systems are served by the vagus nerve (cranial nerve X), while the functions of excretion and control of reproductive organs are served by the splanchnic nerves.

The parasympathetic nervous system is designed to promote highly specific regulation of individual organs: (1) parasympathetic preganglionic fibers are long and travel to specific ganglia linked to specific organs; (2) postganglionic fibers are short and are sometimes found entirely within the innervated tissue; and (3) the ratio of pre- to postganglionic fibers is about 1:3, with one preganglionic fiber affecting only a single organ.

Ganglionic Blocking Agent

Trimethaphan camsylate blocks transmission of impulses at both sympathetic and parasympathetic ganglia, and is used exclusively for the treatment of hypertensive emergencies. It has an immediate onset of action when administered as a continuous infusion (see Table 25-8). The resulting dramatic reduction of BP requires intra-arterial monitoring. The main disadvantage is that the drug must be administered with the patient supine to avoid profound postural hypotension. It has been shown to be useful for acute BP reduction in patients with acute aortic dissection. Other disadvantages include the potential for tachyphylaxis after sustained infusion (48 hours), the appearance of side effects associated with parasympathetic and sympathetic blockade, and histamine release.

Targets: Pharmacodynamics

Ganglionic blockers act by blocking the transmission at the sympathetic and parasympathetic ganglia in the autonomic nervous system; they block cholinergic responses mediated by nicotinic acetylcholine receptors (nAchRs). Hexamethonium blocks synaptic transmission in autonomic ganglia and (in higher concentrations) at the skeletal neuromuscular junction by a nondepolarizing postsynaptic action (Milne and Byrne, 1981). The nAChRs belong to the superfamily of cys-loop receptors and are involved in many physiological functions, including the regulation of neuronal excitability and neurotransmitter release (Albuquerque et al., 2009; Dineley et al., 2015). There are 17 different nAChR subunits (α2–10 and β2–4, γ, δ and ε) (Millar and Gotti, 2009), which through combination as either homo- or heteromeric complexes into multiple functionally diverse pentameric receptors provide the diversity of these receptors in the mammalian nervous system. The predominant subtypes functionally expressed in the brain are categorized as α7 subunit-containing receptors, or those composed of both α and β subunits, including α4β2 and α3β4, which may also contain other subunits such as α2, α5, α6 and β3; the α7 subunit-containing receptors may be either homo- or heteromeric. The α4β2 receptor subtype is the major nAChR subtype in the brain, while the α3β4 nAChR is the ganglionic receptor in the peripheral nervous system. The adult-type muscle nAchR comprises (α1)2β1εδ and are blocked by α-bungarotoxin (Nirthanan and Gwee, 2004) as well as by tubocurarine and the more modern neuromuscular blocking agents (Bowman, 2006). Neuronal nAChRs are divided into those that are sensitive to blockade by α-bungarotoxin, made up of α7, α9 and α10, and those that are insensitive to this toxin and that are heteromeric combinations comprising α2-α6 and β2-β4 subunits (Zoli et al., 2015). Hexamethonium is described as a non-selective blocker of nAChRs, blocking both muscle type (α1)2β1εδ and neuronal nAchR expressed in Xenopus oocytes. Although hexamethonium is typically classified as a ganglionic blocker (Paton and Perry, 1953), its inhibitory potencies at muscle-type receptors, α4β2-type receptors, and α3-containing receptors are similar (Papke et al., 2010) suggesting its apparent selectivity for the ganglion in vivo must be determined by other factors, such as enhanced release of acetylcholine as a result of blockade of pre-junctional nACh at the skeletal neuromuscular junction (Tian et al., 1997). Hexamethonium blockade of α3β4 receptors appears to be non-competitive (Xiao et al., 1998), and the general view is that it blocks the ion channel (Prior et al., 1997; Xiao et al., 1998). Its nAChR receptor promiscuity is illustrated by its blockade of α4β2 receptors (noncompetitively) (Eaton et al., 2003; Wu et al., 2006); and α4β4 receptors (competitively) (Wu et al., 2006).