As the olfactory nerve fibres run from the nose to the brain they pass through holes in the skull that form part of the cribiform plate. Consequently, a severe jar to the head may shear the nerves against the skull, severing or damaging the nerve processes, which usually results in a permanent loss of smell and, because smell and taste are intimately linked, it can also lead to a loss of taste.
Olfactory neurones that possess different kinds of receptors are randomly distributed across the olfactory epithelium. In the brain, however, they sort themselves out, with cells that express the same type of receptor all converging on the same place. The olfactory neurones are unique among nerve cells in that they turn over very rapidly. Each lives only about sixty days and is then replaced by a new neurone that differentiates from an olfactory stem cell. To preserve the map in the brain, replacement nerve cells that bear the same kind of receptors must always find their way to the same place in the olfactory epithelium. How this complex rewiring is achieved is still a mystery.
The King of Fruits
Like most sensations, if you are exposed to a constant smell you gradually become accustomed to it and eventually no longer perceive it. Most people fail to notice their own body odour, or even the perfume they are wearing after a while. But some smells linger longer than others. The durian is revered in South-East Asia as the most delicious of fruits. It is also one of the smelliest – so pungent, in fact, that it is banned from airplanes and hotels. I once came across a durian in a Chinese market in London and having heard of its reputation as the King of Fruits, I bought it and took it back with me on the train to Oxford. During the hour-long journey, the busy rush-hour carriage slowly emptied as the distinctive smell of the durian escaped from my bag. By the time I arrived, I was sitting in solitary state and the smell was overpowering – an indescribable mixture of smelly socks and rotting food that was so disgusting I could not tolerate the idea of having it in my house and instead left it at the lab. Next morning, when I entered the room I reeled back in shock, hit by an overpowering stench. The plan had been to taste the fruit at lunchtime, but long before that the smell had crept down the corridor and penetrated to the front lobby, and people were asking ‘What’s that funny smell?’ Rapid action was needed. So, you may well ask, was it really so delicious? Alas, to me the taste was far less memorable than the stench and not particularly pleasant. I am not alone; the French naturalist Henri Mouhot remarked, ‘On first tasting it I thought it like the flesh of some animal in a state of putrefaction.’ Clearly, it is a taste that has to be acquired.
Touched
From the caress of a loved one, to the feel of the wind on our cheek or the crush of a bear-hug, touch plays an important part in all our lives. Sense organs in our skin respond to such mechanical forces with an electrical change, triggering nerve impulses that relay information back to the spinal cord and brain. Like other sensory nerves, impulse frequency is graded according to the stimulus strength, with lighter touches evoking fewer impulses than stronger pressures. Touch receptors also adapt to continuous stimulation, which explains why we do not notice the pressure of the clothes we wear.
Exactly how mechanical energy is transformed into electrical energy remains a puzzle, but it is clear that mechanically sensitive ion channels are somehow involved. Recent studies suggest that these channels are attached to the extracellular surface of the cell by a gating tether, in an arrangement similar to that found in the hair cells of the ear. Pressure on the cell membrane is thought to tug on the tether, distorting the structure of the channel so that it opens. The more the membrane is deformed, the more channels are likely to be activated and the greater the excitation of the nerve. Sometimes nerve endings sensitive to mechanical force are packaged into specialized structures that enhance their ability to detect changes in pressure or vibrations such as those that arise when you stroke your fingers across a rough surface. However, the end result is the same: a mechanical stimulus elicits an increase in action potential frequency in the sensory nerve.
Some Like it Hot
Our skin not only contains receptors sensitive to pressure, but also to temperature and painful stimuli. Bite into a habenero chilli pepper and it explodes in your mouth like a firebomb. Its burning pain comes from the chemical capsaicin it contains and different varieties of pepper have different amounts of capsaicin, which explains their very different potencies. In 1912, Wilbur Scoville calibrated the strength of chillies by measuring how much an extract of the pepper must be diluted until it was barely detectable when placed on the tip of the tongue. On the Scoville scale, the mild bell pepper notches up less than one heat unit, a jalapeño pepper has 2,500 to 5,000 units, and the famously incendiary Bhut Jolokia well over a million. The potency of pepper sprays used to repel grizzly bears, elephants and human attackers can be even higher: the weapons-grade pepper spray used by the Indian army cracks in at two million Scoville units.
When Mike Caterina and David Julius first isolated the capsaicin receptor, it turned out to be an ion channel. Binding of capsaicin opened the pore and stimulated electrical activity in the sensory nerve. The channel was also opened by noxious heat. So the reason chilli peppers taste so hot is that they open the same ion channel as high temperature and because the brain cannot tell the difference between the two stimuli it interprets them both as heat. These channels are not just found in the tongue, they are also present in the skin of your fingertips, face and other sensitive parts of the body – as unfortunate men who have been chopping chilli very quickly find out if they forget to wash their hands before visiting the lavatory. Unlike humans, birds are not sensitive to chilli because they have a mutation in the channel that renders it less sensitive to capsaicin. This is highly advantageous to the plant, for their seeds are spread by wild birds. It is also why it is recommended to deliberately add chilli powder to bird food to deter squirrels from stealing it.
Just as chilli stimulates hot receptors, so other chemicals interact with receptors that sense cold, fooling the body into thinking the substance is cool. The minty, fresh taste of menthol, found in peppermint oil, arises from the fact it activates an ion channel that detects cold temperatures. This channel is structurally very similar to the capsaicin receptor and in fact we now know that there is a whole family of such channels, called TRP channels, each of which detects a different shade of temperature. Many of these channels are also sensitive to a range of pungent or painful chemicals – not just capsaicin, but substances such as wasabi (the hot Japanese horseradish), mustard, garlic and camphor.
Some snakes have exploited the ability of TRP channels to sense heat to produce natural thermal-imaging cameras that enable them to detect the body heat of their prey and so track their movements and strike accurately even in the dark. The Western diamond-backed rattlesnake, a pit viper, is unmatched in its sensitivity to infrared radiation, being able to detect a change in temperature as small as 0.01 °C. It has two exquisitely sensitive heat sensors, known as pit organs, which lie on either side of its head. These consist of spherical pits, open to the outside, within which a thin heat-sensitive membrane is suspended. Sensory nerve endings ramify through the membrane, their tips crowded with a type of TRP channel known as TRPA1, which serves as the heat sensor.12 It is postulated that heat activates the TRPA1 channels, stimulating firing of the sensory nerve and alerting the snake that its prey – or a predator – is present. Vampire bats also use TRP channels to home in on their warm-blooded prey; they are found in specialized heat-sensing organs located around the bat’s nose.
But TRP channels are not only used to sense temperature. Those sensitive to thermal extremes also serve as pain receptors and when they are stimulated we feel it hurts. This explains why it is difficult to discriminate between extreme heat and intense cold – between fire and ice. One feels only pain. As Shelley eloquently put it, ‘the bright chains eat with their burning cold into my bones’.
Such a Pain
Pain can be extremely useful – it is a valuable alarm
system that signals danger. It tells us that the pan is hot; that our toes are in the fire; that straining too hard will tear our muscles; that we have an infection or a wound. Without it you may be burnt, develop suppurating sores, or walk around with broken limbs, causing further damage. Pain also reminds us to allow damaged parts of the body to heal. A common side-effect of diabetes is the loss of sensation in the feet and legs. As a consequence, blisters, sores and minor injuries can go unnoticed, leading to infections that ultimately may necessitate amputation of the affected limb.
In addition to TRP channels, one of the ten kinds of human sodium channel is involved in the perception of pain. This channel, known as Nav1.7, fails to work in some people. Because their pain nerve fibres can no longer conduct action potentials, they are unable to feel pain, although their sensitivity to touch, temperature, pressure and so on is completely normal. This is far from a blessing, for pain is a valuable warning and bruised and broken limbs may go unnoticed in people who lack functional Nav1.7 channels. Indeed, scientists first identified the role of the channel in pain sensation by studying the family of a young Pakistani boy who made a living by stabbing knives into his arms, or walking on burning coals, in a gruesome form of street theatre. On his fourteenth birthday he jumped off a house roof to prove just how tough he was. He died from his injuries, which mercifully he was unable to feel.
Equally disabling is the opposite condition in which the Nav1.7 sodium channels are permanently activated. This condition is known as erythermalgia and it runs in families. Patients suffer episodes of intense debilitating pain, associated with redness and burning sensations in their hands, arms and legs. They complain that they feel as if hot lava had been poured over their body, as if their feet were on fire or of the sensation of walking on hot sand. These symptoms tend to be provoked by warm weather, exercise and the use of bed sheets, and many sufferers are unable to wear shoes because of the pain. It seems Nav1.7 sets the gain on pain – too much channel activity and you will be in permanent pain, too little and you will be always anaesthetized. Interestingly, a common variant in the Nav1.7 gene alters your pain threshold and could explain why the same stimulus feels more painful to some people than to others.
All pain comes from the brain. It is our brain that receives messages from nerve fibres, telling us we have stubbed our toe, and many brain areas are involved in our experience of pain; they tell us where the pain is, how much it hurts, and what kind of pain it is – sharp, burning or just a dull ache. Our perception of pain is also highly variable. Even if the input signal from our sensory nerve endings is identical, the way the signals are processed is powerfully influenced by our attention, mood and expectation and this can dramatically alter the pain we experience. Our emotions can make a placebo pill an effective painkiller even though it contains no active ingredient, and, conversely, fear of pain can sharpen its impact.
The main problem with pain is that once we have registered its message we are unable to switch it off. Worse still, in some unfortunate people the pain may remain even after the body has healed. Such chronic pain is very common, and is experienced by as many as 15 per cent of adults. This can be devastating and may ruin their lives. Billions of dollars are spent on pain medication every year, but many painkillers are not very effective and some of them, such as those derived from opium, have addictive properties. Better drugs are urgently needed, especially for treating chronic pain, which is often not ameliorated by current therapies. Because Nav1.7 is mainly confined to pain neurones, a drug that specifically blocks these channels might be able to tune out pain without causing side-effects.
What a Relief
When I was a child, I dreaded a visit to the dentist as it was often a painful experience. No longer. Modern dentistry has been completely transformed by the introduction of new and better local anaesthetics. Even the removal of a nerve from a root canal is painless – the worst sensation is the sharp pinprick as the injection is given, and that too is partially numbed by application of a topical anaesthetic. Most local anaesthetics act by blocking sodium channels, preventing conduction of nerve impulses from local nerve endings in the teeth to the brain. Dentists commonly use lidocaine because it acts very rapidly. The problem with such drugs, however, is that they do not just inhibit electrical activity in pain fibres, they also affect the other sensory and motor nerve fibres so that some hours after we have visited the dentist we still have a lopsided smile and our jaw feels numb. What is needed is an anaesthetic that is specific for the sensory nerves.
One way to find this is to identify the types of ion channels specific to sensory nerves and then find a drug that selectively blocks them. Currently, the best target seems to be Nav1.7, and several drug companies are currently seeking specific inhibitors of this channel. This is far from easy as the drug must also be able to penetrate the sheath surrounding the nerve, must not be broken down by the body too quickly, and preferably should retain its activity when taken by mouth. Developing any new drug also takes a long time and is extremely expensive. Consequently, it may be some time before we no longer suffer a frozen jaw after a visit to the dentist.
The Sensational Brain
Information from our sense organs travels via the sensory nerves to the brain encoded as electrical impulses. Bypassing the sense organs and stimulating the sensory nerves directly therefore evokes a sensation, as Isaac Newton vividly demonstrated in the mid-1660s. He records how he slid a bodkin (a small needle) between his eyeball and the back of the eye socket and found that when he pressed on it ‘there appeared severall white darke & coloured circles’. It is not necessary to perform such a dangerous experiment, however, to see coloured circles – simply gently pressing on the closed eyelid will do it. The pressure stimulates the retina, and thus the optic nerve, and is seen as light. Direct electrical stimulation of the region of the brain concerned with vision has the same effect, even in the blind.
Newton also records how the ‘circles were plainest when I continued to rub my eye [with the] point of [the] bodkine, but if I held my eye & [the] bodkin still, though I continued to presse my eye [with] it yet [the] circles would grow faint & often disappeare untill I removed [them] by moving my eye or [the] bodkin’. As you will by now appreciate, a common theme in the nervous system is that the response to a continuous stimulus gradually weakens. We are preprogrammed to respond most strongly to changes in our environment and cease to pay attention if nothing new happens, a phenomenon that has a clear evolutionary advantage.
Sensory experience, then, is coded in electrical signals. It is the brain that interprets this barrage of nerve impulses, and deduces – on the basis of where they come from – what they mean. When the brain fails to attend to its inputs we may stare at the world but fail to see what is there, and illusions arise when signals conflict. Nor is the brain merely a receiver, for it can tune the sensitivity of our sense organs and modify the information they receive. Our perception of sights, sounds, scents and so on is thus the result of a two-way collaboration between our sense organs and the brain. So let us next look at the role the brain plays in this sensational dance and how it modifies and shapes the fractured information supplied by our sense organs, and weaves it together to produce a complete sensory picture of the world. To do so, we must first understand how the brain is wired up.
10
All Wired Up
Men ought to know that from the brain, and from the brain alone, arise our pleasures, joys, laughter and jests, as well as our sorrows, pains, griefs and tears. Through it in particular, we think, see, hear, distinguish the ugly from the beautiful, the bad from the good, the pleasant from the unpleasant.
Hippocrates, On the Sacred Disease
Hello. I am delighted to meet you – and particularly pleased you have made it this far. I hope it has been an interesting journey. Or perhaps you have just picked up this book and, riffling through the pages, have arrived at this one? Whichever it is, take a moment to consider how astonishing it is that I can communic
ate with you so easily across space and time. A vast number of obscure electrical miracles taking place in your brain enable me to do so.
As you read (or listen) to my words, the sensory cells in your eyes or ears are busily engaged in detecting information encoded as light or sound and transforming it into electrical signals. But that’s only the start of the process – that information is then converted into a chemical signal and back again into an electrical one multiple times as it travels from sense organ to brain. And information that was first deconstructed into small manageable chunks of data is then processed and reassembled to form several sensory maps in the surface layers of your brain. Even more extraordinary, this information – this pattern of electrical signals flying around your nerve cells – is then interpreted as language and yet more sparks fly as you recognize my words and understand what I mean. If you like what I say, you might smile; and if you don’t understand me or think my words facile you may by now be feeling frustrated or irritated – you may even (I hope not) be bored. And this too, these emotions my words trigger, are again produced by chemicals sloshing around your brain stimulating yet more nerve cells to fire. But the truly astonishing thing, most extraordinary of all, is that the person talking to you, writing these words – and indeed you yourself – is locked inside a small lump of jelly that fits neatly into your cupped hands and weighs no more than about 3 pounds: the brain. We are electrical beings, you and I, and we constitute no more than an unimaginably complex and continuously changing pattern of electrical and chemical signals.
The Spark of Life: Electricity in the Human Body Page 23
