*1 From a Greek word meaning “to sow,” the term “sperm” is first recorded in English in The Canterbury Tales. In those days, and at least until the time of Shakespeare, it was generally pronounced “sparm.” Spermatozoa, the more formal designation, dates only from 1836, in a British anatomical guide.
*2 Doctors also sometimes use the terms “binovular” for fraternal twins and “uniovular” for a matched set.
19 NERVES AND PAIN
Pain has an element of blank;
It cannot recollect
When it began, or if there were
A day when it was not.
—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.”