The vagus nerve: a journey

A former student, now a Head and Neck Surgeon in Liverpool, has asked me to give a talk to his colleagues. Here it is. Even if you’re neither medic nor zoologist you might get something from it, particularly the way that words carelessly used can lead to erroneous inferences. 

This is the story of the tenth cranial nerve and me.

You won’t hear anything useful for your research project or your next paper. This is not likely to result in earth-shattering developments in head and neck surgery. It is rather a series of speculations and insights arising from half a century of asking “why?”.

As a clinical student 1972-75 at King’s College Hospital in south London it gradually dawned on me that medical practice was not to my taste, so in the final year I did some thinking. The things that took my fancy in Cambridge were, first, the introductory anatomy lecture in which the Professor of Anatomy told us about our place in nature with other primates (apes not archbishops); and, second, embryology, that is to say, how we come to be what we are. I guess our medical student cohort was one of the last to study embryology in any depth, examining serial sections of pig embryos every Monday afternoon for a term. 

But the most significant Cambridge influence was the person of Max Bull, the senior non-professorial anatomist, a gifted analytical teacher, and my supervisor. “If that is what an anatomist is and does,” I must have thought, “then an anatomist I shall be”.

In 1976 I started work as Anatomy Demonstrator (Temporary Lecturer) at the new medical school in Nottingham. I stayed for 11 years. In 1988 I took up the Chair of Anatomy at the Royal College of Surgeons in Ireland, which was and remains the biggest undergraduate medical school in Ireland, despite its name. After 16 years I came back to England as the foundation anatomist of the new Nottingham graduate entry medical school sited in Derby.

I was intrigued by a few things throughout this time: for example, the systematic arrangement of brain stem nuclei; that structurally we haven’t changed much since reptiles; and the ways that different species, different chordates even, handle the perception of vibration in the external environment (we call it hearing). But most of all, the vagus.

A motor nerve?

The tenth cranial nerve arises from the medulla by a series of rootlets posterolateral to the olive. The nerve passes through the jugular foramen and runs in the carotid sheath down to the mediastinum. It sends branches to ear, pharynx, and larynx, and forms a plexus around the oesophagus becoming ever more intimately involved with the gut tube as part of the myenteric plexuses of foregut and midgut – all the way to the splenic flexure of the colon.

Good Heavens, this is boring, isn’t it?

I could go on in mind-numbing detail that would have you reaching for the knife with which to slit your throat. But have you noticed that already our view of the vagus is coloured by that textbook account? The brain-to-periphery description implants in our minds the vagus as a motor nerve. 

This is reinforced when we hear physiologists and physicians tell us that vagal impulses slow the heart rate. That is how my undergraduate course first introduced the vagus to me. I heard that it is a parasympathetic nerve (motor), part of the autonomic nervous system that slows the heart (motor).

In 1969 I accepted this without question. After all, I was hearing it from eminent scientists – at least three of them Fellows of the Royal Society, and this 19-year-old freshman from remote Cumberland had other priorities surrounded as he was by the delectable delights of Cambridge.

But the vagus crept up on me. It has a role in the ear. It supplies the lateral line in fish, a system of receptors extending along the side of the body having something to do with picking up vibrations from the aquatic environment. This was intriguing.

Then I saw with my own eyes the asymmetry of the recurrent laryngeal branches – not only in the cadaver but also in serial sections of pig embryos. Thus I came to see how the branchial arch apparatus – fish again – stamped its presence on human anatomy. I began to appreciate that we carry our evolutionary history with us, and much of that history impinges on our structure and function. I began to ponder von Haeckel’s dictum “ontogeny repeats phylogeny”..

Being an Ear, Nose and Throat intern in 1975-76 might have stimulated further interest in the vagus, but keeping on the right side of irascible consultants, looking after patients some of whom I was pumping full of very nasty anti-cancer drugs, and coping with life in general meant there was no time for speculative thinking. Neither was there in Nottingham: I was learning the ropes, interested in university politics, doing a PhD and being a husband and father. 

It was in Dublin from 1988 onwards that I began seriously asking “why?”.

A shifting view

My view of the vagus was changing. I began to see that the vagal functions I’d first been introduced to by physiologists and physicians couldn’t be that important. How could they be when a transplanted heart does perfectly well without any innervation whatsoever? Can you imagine the surgeon suturing tiny strands of nerves and expecting axons to grow down them? So much for cardiac physiology as taught. And then there’s vagotomy (Helicobacter pylori hadn’t been invented then) – how did that affect the distal gut tube? 

You can see I was still in the way of thinking of the vagus as a predominantly motor nerve, reinforced by the appreciation of its role as the nerve of phonation and swallowing. Of course I was aware of its sensory functions, not least because of referred pain to the ear from pharyngeal disease, but they seemed somehow less significant.

I couldn’t see how to put all this together. Phonation, swallowing, external and middle ear, heart, stomach, foregut, midgut? No wonder the vagus is so-called. Why not hindgut? How do we know that vagal fibres go no further than the splenic flexure? In the words of Victor Meldrew, I don’t believe it. Is it merely inference, like so much else? How does it fit with the lateral line? 

Enlightenment

Then one night I had a light-bulb moment as I was soaking in the bath.

What does the heart do? Pumps nutrients round the body.

What do babies use their vocal cords for? To cry for sustenance.

What is the gut tube for? Absorption of nutrients. 

What does the vagus do to the pyloric sphincter? Relaxes it to allow food to move on for digestion.

What do we use our ears for? To pick up vibrations from the environment.

Why? In the search for food and to avoid becoming food for other creatures.

What is the lateral line in fish for? To pick up vibrations from the environment.

Why? Shoaling in the corporate search for food.

What is the function of the pharyngeal musculature supplied by the vagus? Ingestion, swallowing of food.

The vagus is the nerve of nutrition.

All the structures it supplies are in some way connected to embryonic endoderm derived from the yolk sac. Can the vagus be summed up as the nerve of the yolk sac?

What about sensory?

As a result of teaching histology, I began to think about the myenteric plexuses. My passing interest in invertebrates of the aquatic deeps led me to realise that the plexuses function as a network of mini-brains – a gut brain – coordinating local reflex peristalsis, no motor impulses from the central nervous system being necessary. Also, there must be visceral sensory fibres from gut tube via myenteric plexuses to CNS for coordination and for such as emergency shutdown, and these must be joined by fibres from other abdominal viscera.

I began to see that distal to branches to laryngeal and pharyngeal musculature, the vagus was very significantly a sensory nerve. I had rid myself of the motor obsession. 

The vagus is implicated in a number of common conditions: oesophageal reflux of course, chronic hiccupping, gastroparesis and more. Here are vagal sensory functions working as it were too much or too little. As for the gut brain concept, this has blossomed over recent years. Having been regarded with suspicion as something promoted by sandal-wearing, yoghurt-knitting alternative medicine practitioners, it’s now right up there with the big boys and girls.

We talk of gut feelings, gut reactions. We know that the state of our guts affects our moods and feelings, the inference being that vagal inputs connect to the limbic system. As you may know, this is an up-and-coming research area in psychiatry. Certainly my gut is an effective warning system in all sorts of ways. Unfortunately, we know next to nothing about how visceral sensation in general and vagal inputs in particular are handled centrally – a recurring lament.

What about vagal stimulation for epilepsy? The question is really, I suppose, how do vagal sensory impulses reach the epileptic focus? As I say, our knowledge of visceral sensory central connexions is minimal, and I don’t know the answer. Judging from a survey of online publications, neither does anyone else: there’s a good deal of fudging. Perhaps this treatment regime arose, like many others, from a serendipitous observation.

Odds and ends

I don’t much care for the terms autonomic, sympathetic, parasympathetic, and I’m pleased to note that the US NIH agrees with me. They are pretty harmless when used of functions or modalities, but cause trouble when used, as they sometimes are, of structures – for example “the vagus is a parasympathetic nerve”, giving the impression that it is entirely a motor nerve. Autonomic means visceral motor, cell bodies of presynaptic (a better term than preganglionic) neurons being in the brain stem salivatory nuclei, the dorsal motor nucleus of the vagus, the sacral lateral grey horn, or for sympathetic impulses the lateral grey horn of the thoracolumbar region of the cord. 

So as terms describing modality I can just about live with them. But they lead to error if used of sensory fibres. One can fall into the trap of thinking that there are pre- and postsynaptic sensory fibres, as with visceral motor fibres. Not so. Sensory systems have no peripheral synapses. Primary sensory neurons, no matter what their origin or modality, are morphologically either pseudounipolar or bipolar with cell bodies in sensory ganglia (no synapses) just outside the central nervous system – dorsal root ganglia or the sensory ganglia of those cranial nerves that convey sensory fibres. 

What about the splenic flexure business? Is this really as the books say the limit of vagal gut tube territory? Such statements are often copied from text to text with no sources given. A survey of eighteenth and nineteenth century literature would be interesting to see when the story appeared. But assuming that the tale is true, perhaps the entire distal gut tube is a cloacal derivative with visceral supply from the lateral grey horns of the sacral spinal cord.

I find the sacral spinal cord quite fascinating. Did you know that in birds the terminal (sacral equivalent) spinal cord is separated from the rest of the cord by the glycogen body? Its function remains mysterious. According to Wikipedia (so it must be true) glycogen bodies may also have been present in dinosaurs from which birds are descended. But back to mammals where there is no glycogen body, but where there is nevertheless something different about the sacral cord. It develops not by folding of surface neuroectoderm to form a tube like the rest of the CNS, but by direct in situ differentiation. What to make of this I have no idea except that the sacral cord is peculiar.

Functionally, it is a cloacal brain responsible for sphincters and sex. So if you like, and I do like, we have one brain for controlling gut tube entry, and another brain for controlling gut tube exit. This cloacal brain does not need connexions with the rest of the CNS, as in patients with spinal cord transactions that isolate the sacral cord: it comes into its own with automatic sphincter control. How far back in reptilian/mammalian history this developed I do not know, but given the resonances between mammalian and avian sacral regions, perhaps it has something to do with laying eggs. It would be interesting to know more about the innervation of cloacal derivatives in egg-laying mammals. 

Finally in the nether regions of the trunk, vagal sensory fibres supply the uterus. What for? Why? They might account for the reports of women with spinal cord transection who nevertheless experience orgasm, the vagus being the afferent pathway rather than the spinal cord..

These ruminations lead me to think that we should consider, and teach, the nervous system as it evolves.

When we are simply tubes on the seabed waiting for currents to waft plankton our way for sustenance, we don’t need voluntary muscles at all. We need only the myenteric plexuses to deal with peristalsis. When we need to seek food and avoid being food for other creatures, then we need to move, so the body wall and its limb appendages need muscles and nerves. Thus we have the somatic nervous system.

Instead of teaching somatic first, then visceral, we should teach it as it (in my scheme) evolves. And when it comes to the somatic system, we tend to start with a reflex, so sensory first then motor. But functionally motor is more significant – we have to move to eat – so we should start with that.  But changing the minds of academics who are concerned only with their tiny area of interest is a bit like Northern Irish politics.

Drawing my thoughts together

I hear you say that none of this matters. It doesn’t help patient care, it doesn’t aid my research programme, it doesn’t get me a higher degree. 

It might, though. 

We are so busy scurrying around collecting data about detail that we ignore the big picture stuff. Who knows where seeing connexions might lead? If we’d never speculated about connexions we’d still be scrabbling round in caves, we’d not have penicillin, we’d have no smallpox vaccine, we’d have no theories of relativity. My big picture for the vagus is that it’s the nerve of nutrition, possibly even the yolk sac nerve.

Stepping outside the territory of anatomy, this kind of synthetic big picture thinking has relevance to fetomaternal immunology, still rather mysterious. Why is the fetus, a foreign organism, not normally rejected? One of the factors is that the immunology of the fetomaternal interface has things in common with that of colonial invertebrates that rub up against each other quite happily recognizing their sameness rather than, as in classical mammalian immunology, obsessing about their difference. 

Erroneous perceptions distort our capability for analytical thought. I ask for care in the use of words. As I hope I’ve shown, a lack of precision can so easily lead to fallacious conceptual thinking – for example confusion of fibres and nerves, ganglia and synapses. I hope too I’ve managed to let you see how easily we can be misled by the way information is presented in a text. It’s worth remembering that definitions and concepts are products of the human mind, and the human mind does not always see things clearly. 

As I said I’m probably one of the last generation of medical students to have studied embryology in any detail. I found it quite fascinating and I hope I’ve passed on that enthusiasm to some of my students. Is it useful? Well, it helps answer the “why?” question. It’s a pity that comparative anatomy and embryology have disappeared from undergraduate medical courses, for the more we specialize, the more limited our visual fields become and the more difficult it is to see connexions. We ignore our zoological history to the detriment of broadness of vision.

A plea

We need people who are paid to sit back and think big picture. We need people to make interdisciplinary connexions through blue-sky speculation that our increasingly frenetic research programmes have no time for, driven as they are by the need to satisfy grant-giving bodies, drug companies and the demands of publication. I suppose it’s a kind of academic relaxation I’m asking for – relaxation being something else that the vagus promotes. Regrettably, I don’t see that happening soon.

I have this feeling I was born a hundred years too late. Or too early.

4 thoughts on “The vagus nerve: a journey

  1. 50 years ago when we were undergraduates the Cambridge professor of anatomy was Richard Harrison (later knighted). There were rumours that he had live dolphins in tanks in the Downing Street site which probably would be frowned upon today. Apparently he was researching the “diving reflex” which brings us back to the Vagus which, as you say, slows the heart possibly enabling mammals to remain underwater for longer.

    • Thank you, Dr Selley. Another connexion. I shall use it. The lecture to which I refer was in October 1969. AFAIK the dolphins were up there. The Anatomy Department at Cambridge, as elsewhere, is now no more, consumed by the Department of Physiology, Development and Neuroscience.

  2. Good to see you are still thinking about this.
    May I propogate this more widely?
    It may be you were born at the right time, or perhaps too early.

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