The body, p.34
The Body, page 34
—EMILY DICKINSON
PAIN IS A strange and troublesome thing. Nothing in your life is more necessary and less welcome. It is one of humanity’s greatest preoccupations and bewilderments and one of medical science’s greatest challenges.
Sometimes it saves us, as we are vividly reminded each time we recoil from a jolt of electricity or try to walk barefoot across hot sand. So sensitive are we to threatening stimuli that our bodies are programmed to react to and withdraw from painful events before our brains have even received the news. All that is unquestionably a good thing. But quite a lot of the time—for up to 40 percent of people, by one calculation—pain just goes on and on and seems to have no purpose at all.
Pain is full of paradoxes. Its most self-evident characteristic is that it hurts—that’s what it is there for, after all—but sometimes pain feels slightly wonderful: when your muscles ache after a long run, say, or when you slide into a bath that is at once unbearably hot but also, somehow, deliciously not. Sometimes we cannot explain it at all. One of the most severe and challenging of all pains is said to be phantom limb pain, when the sufferer perceives agonies in a part of the body that has been lost to accident or amputation. It is an obvious irony that one of the greatest pains we feel can be in a part of us that is no longer there. Worse, unlike normal pain, which usually abates as a wound heals, phantom pain may go on for a lifetime. No one can yet explain why. One theory is that in the absence of receiving any signal from the nerve fibers in the missing body part, the brain interprets this as an injury so severe that the cells have died, and so sends out an unending call of distress, like a burglar alarm that won’t turn off. If surgeons know they are going to amputate a limb, they now often numb the nerves in the affected limb over a period of days beforehand to prepare the brain for the oncoming loss of feeling. The practice has been found to greatly reduce phantom limb pain.
If phantom pain has a rival, it may be said to be trigeminal neuralgia, named for the principal nerve of the face and historically known as tic douloureux (literally “painful twitch” in French). The condition is associated with a sharp, stabbing pain across the face—“like an electric shock,” in the words of one pain specialist. Often there is a clear cause—when, for instance, a tumor presses against the trigeminal nerve—but sometimes no cause can be discerned. Patients may suffer periodic attacks, which can start and stop abruptly, without warning. These can be excruciating, but then they may cease altogether for days or weeks before coming back again. Over time, the pain may wander around the face. Nothing can explain why it wanders or what makes it come and go.
Exactly how pain works is, as you will gather, still largely a mystery. There is no pain center in the brain, no one place where pain signals congregate. A thought must travel through the hippocampus to become a memory, but a pain can surface almost anywhere. Stub your toe and the sensation will register across one set of brain regions; hit it with a hammer and it will light up others. Repeat the experiences, and the patterns may change yet again.
Perhaps the weirdest irony of all is that the brain has no pain receptors itself, yet it is where all pain is felt. “Pain only emerges when the brain gets it,” says Irene Tracey, head of the Nuffield Department of Clinical Neurosciences at the University of Oxford and one of the world’s leading authorities on pain. “The pain might have started in the big toe, but the brain is the thing that gives you the ouch. Up until then it is not pain.”
All pain is private and intensely personal. Meaningful definition is impossible. The International Association for the Study of Pain summarizes pain as “an unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage,” which is to say that it is anything that hurts, or might hurt, or sounds as if it might hurt, or feels as if it might hurt, whether literally or metaphorically. That pretty much covers every bad experience there is, from bullet wounds to the heartache of a failed relationship.
The best-known measure of pain is something called the McGill Pain Questionnaire, devised in 1971 by Ronald Melzack and Warren S. Torgerson at McGill University in Montreal. It is simply a detailed questionnaire that provides subjects with a list of seventy-eight words describing different levels of discomfort—“stabbing,” “stinging,” “dull,” “tender,” and so on. Many of the terms are vague or indistinguishable. Who could differentiate between “annoying” and “troublesome” or “miserable” and “horrible”? Largely for that reason, most pain researchers today use a simpler one-to-ten scale.
The whole experience of pain is obviously subjective. “I’ve had three children and believe me that has changed my experience of where the maximum lies,” says Irene Tracey, with a broad and knowing smile, when we meet in her office at the John Radcliffe Hospital in Oxford. Tracey may be the busiest person in Oxford. As well as her extensive departmental and academic duties, at the time of my visit, in late 2018, she had just moved house, just returned from two trips abroad, and was about to take over as warden (or dean) of Merton College.
Tracey’s working life is devoted to understanding how we perceive pain and how we might ameliorate it. Understanding pain is the hard part. “We still don’t know exactly how the brain constructs the experience of pain,” she says. “But we are making a lot of progress, and I think the whole landscape of our understanding of pain is going to change dramatically over the next few years.”
One advantage Tracey has over previous generations of pain researchers is the possession of a really powerful magnetic resonance imaging machine. In her lab, Tracey and her assistants gently torment volunteers for the good of science by pricking them with pins or daubing them with capsaicin, the chemical behind the Scoville scale and the heat of chilies, as you may recall from chapter 6. Inflicting pain on innocent people is a delicate business—the pain needs to be genuinely felt but for obvious ethical reasons mustn’t inflict serious or lasting damage—but it does allow Tracey and her colleagues to watch in real time how the subjects’ brains respond to pain as it is administered.
As you might imagine, lots of people would love, for purely commercial reasons, to be able to peer into other people’s brains to know when they are feeling pain, or being untruthful, or even perhaps responding favorably to a marketing ploy. Personal injury lawyers would be overjoyed to have pain profiles that they could present as evidence in court. “We are not at that point yet,” says Tracey, with what appears to be a slight air of relief, “but where we are making really rapid progress is in learning how to manage and limit pain, and that is helping lots of people.”
The experience of pain begins just beneath the skin in specialized nerve endings known as nociceptors. (“Noci-” is from a Latin word meaning “hurt.”) Nociceptors respond to three kinds of painful stimuli: thermal, chemical, and mechanical, or at least so it is universally assumed. Remarkably, scientists have not yet found the nociceptor that responds to mechanical pain. It is extraordinary surely that when you whack your thumb with a hammer or prick yourself with a needle, we don’t know what actually happens beneath your outer surface. All that can be said is that signals from all types of pain are conveyed on to the spinal cord and brain by two different types of fibers—fast-conducting A delta fibers (they’re coated in myelin, so slicker, as it were) and slower-acting C fibers. The swift A delta fibers give you the sharp ouch of a hammer blow; the slower C fibers give you the throbbing pain that follows. Nociceptors only respond to disagreeable (or potentially disagreeable) sensations. Normal touch signals—the feel of your feet against the ground, your hand on a doorknob, your cheek on a satin pillow—are conveyed by different receptors on a separate set of A-beta nerves.
Nerve signals are not particularly swift. Light travels at 300 million meters per second, while nerve signals move at a decidedly more stately 120 meters a second—about 2.5 million times slower. Still, 120 meters a second is nearly 270 miles an hour, quite fast enough over the space of a human frame to be effectively instantaneous in most circumstances. Even so, as an aid to responding quickly, we have reflexes, which means that the central nervous system can intercept a signal and act on it before passing it on to the brain. That’s why if you touch something very undesirable, your hand recoils before your brain knows what’s going on. The spinal cord, in short, is not just a length of impassive cabling carrying messages between the body and the brain but an active and literally decisive part of your sensory apparatus.
Several of your nociceptors are polymodal, which means they are triggered by different stimuli. That’s why spicy foods taste hot, for instance. They chemically activate the same nociceptors in your mouth that respond thermally to real heat. Your tongue can’t tell the difference. Even your brain is a little confused. It realizes, at a rational level, that your tongue isn’t literally on fire, but it sure feels that way. What is oddest of all is that the nociceptors somehow allow you to perceive a stimulus as pleasurable if it’s a vindaloo and yelp inducing if it’s a hot match head, even though both activate the same nerves.
The person who first identified nociceptors—who can indeed fairly be called patriarch of the central nervous system altogether—was Charles Scott Sherrington (1857–1952), one of the greatest and most inexplicably forgotten British scientists of the modern era. Sherrington’s life seems to have been lifted straight out of a nineteenth-century boys’ adventure story. A gifted athlete, he played soccer for Ipswich Town while still in school and had a distinguished rowing career at Cambridge. He was above all a brilliant student, winning many honors while impressing all who met him with his modest manner and keen intellect.
After graduating in 1885, he studied bacteriology under the great German Robert Koch, then embarked on a dazzlingly varied and productive career in which he did seminal work on tetanus, industrial fatigue, diphtheria, cholera, bacteriology, and hematology. He proposed the law of reciprocal innervation for muscles, which states that when one muscle contracts, a companion muscle must relax—essentially explaining how muscles work.
While studying the brain, he developed the concept of the synapse, coining the term “synapse” in the process. This in turn led to the idea of proprioception—another Sherrington coinage—which is the body’s ability to know its own orientation in space. (Even with your eyes closed, you know whether you are lying down or whether your arms are outstretched and so on.) And this, in further turn, led to the discovery in 1906 of nociceptors, the nerve endings that alert you to pain. Sherrington’s landmark book on the subject, The Integrative Action of the Nervous System, has been compared to Newton’s Principia and Harvey’s De motu cordis (On the Motion of the Heart) in terms of its revolutionary importance to its field.
But Sherrington’s admirable qualities don’t stop there. He was, by all accounts, a pretty wonderful person: devoted husband, gracious host, delightful company, beloved teacher. Among his students were Wilder Penfield, the authority on memory whom we met in chapter 4; Howard Florey, who won a Nobel Prize for his role in developing penicillin; and Harvey Cushing, who went on to become one of America’s leading neurosurgeons.
In 1925, Sherrington astonished even his closest friends by producing a volume of poetry, which was widely praised. Seven years later, he won a Nobel Prize for his work on reflexes. He was a distinguished president of the Royal Society, a benefactor of museums and libraries, and a devoted bibliophile with a world-class collection of books. At the age of eighty-three in 1940 he wrote a bestselling work, Man on His Nature, which went through several editions and was voted one of the hundred best books of modern Britain at the Festival of Britain in 1951. In it, he invented the expression “the enchanted loom” as a metaphor for the mind. And now, unaccountably, he is almost completely forgotten outside his field and not hugely remembered even there.
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The nervous system is divided in various ways depending on whether you are looking at its structure or its function. Anatomically, it has two divisions. The central nervous system is the brain and spinal cord. The nerves radiating out from this central hub—the ones that reach out to the other parts of your body—are the peripheral nervous system. The nervous system is additionally divided by function into the somatic nervous system, which is the part that controls voluntary actions (like scratching your head), and the autonomic nervous system, which controls all those things like heartbeats that you don’t have to think about because they are automatic. The autonomic nervous system is further divided into sympathetic and parasympathetic systems. The sympathetic is the part that responds when the body needs sudden actions—what is generally referred to as the fight-or-flight response. The parasympathetic is sometimes referred to as the “rest and digest” or “feed and breed” system and looks after a miscellany of other, generally less urgent matters like digestion and waste disposal, the production of saliva and tears, and sexual arousal (which may be intense but not urgent in the fight-or-flight sense).
An oddity of human nerves is that those in the peripheral nervous system can heal and regrow when damaged, whereas the more vital ones in the brain and spinal cord cannot. If you cut your finger, the nerves can grow back, but damage your spinal cord and you are out of luck. Spinal cord injuries are dismayingly common. More than one million people in the United States are paralyzed from them. More than half of spinal cord injuries in America result from car accidents or gunshot wounds, so, as you might expect, men are four times more likely to get a spinal cord injury than women. They are especially susceptible between the ages of sixteen and thirty—just when they are old enough to have guns and cars and foolish enough to misuse them.
Pain, like the nervous system itself, is classified in a multiplicity of ways, and these vary in type and number from authority to authority. The most common category is nociceptive pain, which simply means stimulated pain. It’s the pain you get when you stub a toe or break your shoulder in a fall. It is sometimes referred to as “good” pain, in the sense that it is the kind of pain that tells you to rest the affected part and give it a chance to heal. A second type is inflammatory pain, for when tissue becomes swollen and red. A third category is dysfunctional pain, which is pain without external stimulus and that causes no nerve damage or inflammation. It is pain without evident purpose. A fourth kind of pain is neuropathic pain, in which nerves are damaged or grow sensitive, sometimes as a result of trauma, sometimes for no apparent reason.
When pains don’t go away, pain goes from being acute to chronic. Some twenty years ago, Patrick Wall, a leading British neuroscientist, in an influential book called Pain: The Science of Suffering, maintained that pain beyond a certain level and duration is almost entirely pointless. He noted that nearly every textbook he had ever seen contained an illustration showing a hand recoiling from a flame or hot surface to demonstrate the usefulness of pain as a protective reflex.
“I despise that diagram for its triviality,” he wrote with somewhat startling passion. “I would estimate that we spend a few seconds in an entire lifetime successfully withdrawing from a threatening stimulus. Unfortunately, we spend days and months in pain during our lifetime, none of which is explained by that silly diagram.”
Wall singled out cancer pain as “the apogee of pointlessness.” Most cancers don’t cause pain in their early stages when it might usefully alert us to take remedial action. Instead, all too often cancer pain becomes evident only when it is too late to be useful. Wall’s observations came from the heart. He was dying of prostate cancer at the time. The book was published in 1999, and Wall died two years later. From the perspective of pain research, the two events together marked the end of an era.
Irene Tracey has been studying pain for twenty years—coincidentally almost exactly the period since Wall died—and has seen a complete transformation in that time in how pain is clinically regarded.
“Patrick Wall was in an era when people kept trying to hypothesize a purpose for chronic pain,” she says. “Acute pain has an obvious point: it tells you that something is wrong and needs attention. They wanted chronic pain to have that kind of point, too—to exist for a purpose. But chronic pain has no purpose. It’s just a system gone wrong, in the same way that cancer is a system gone wrong. We now believe that many types of chronic pain are diseases in their own right, something quite separate from acute pain.”
There is a paradox at the heart of pain that makes its treatment particularly intractable. “When most parts of the body are damaged, they stop working—they switch off,” Tracey says. “But when nerves are damaged, they do exactly the opposite—they switch on. Sometimes they just won’t switch off, and that is when you get chronic pain.” In the worst cases, as Tracey puts it, it is as if the volume knob on their pain has been turned all the way up. Figuring out how to turn that volume down has proved to be one of the greatest frustrations in medical science.
Generally, we don’t feel pain in most of our internal organs. Any pain that arises from them is known as referred pain because it is “referred” to another part of the body. So the pain of coronary heart disease, for instance, may be felt in the arms or neck, sometimes in the jaw. The brain is also without feelings, which raises the natural question of where do headaches come from? The answer is that the scalp, the face, and the other outer parts of the head all have plenty of nerve endings—more than enough to account for most headaches. Even if it feels as if it were coming from deep within your head, a routine headache is almost certain to be a surface feature. Inside your skull, the meninges, the protective covering of the brain, also have nociceptors, and pressure on the meninges is what causes pain from brain tumors, but luckily that is something most of us will never have to experience.
You would think that if any condition is universal, it is the headache, but 4 percent of people say they have never had one. The International Classification of Headache Disorders recognizes fourteen categories of headaches—migraine, trauma-induced headache, infection-induced headache, disorder of homeostasis, and so on. However, most authorities divide headaches into two broader categories: primary headaches, such as migraine and tension headaches, which have no direct, identifiable cause, and secondary headaches, which arise from some other precipitating event, like an infection or tumor.
