Will there ever be a cure for chronic pain?

By Sophie Elmhirst

Peter McNaughton, a professor of pharmacology at King’s College London, is a devoted optimist. He acknowledges that his positivity can sometimes seem irrational, but he also knows that without it he wouldn’t have achieved all that he has. And what he’s achieved is quite possibly monumental. After decades of research into the cellular basis of chronic pain, McNaughton believes he has discovered the fundamentals of a drug that might eradicate it. If he’s right, he could transform millions, even billions, of lives. What more could anyone hope for than a world without pain?

McNaughton, nearly 70, is long-limbed, grey-haired and bespectacled. Though he has lived in London for decades, his voice still carries the cheery cadence of his native New Zealand. He wears blue Levis and black Nikes and delights in a late-blooming informality after years of heading university departments and turning up in a suit. Now, running his own lab, he can dress as he likes. On a Friday morning in April he waited for his young team to arrive at the modern, red-brick building in south London where he conducts his research. (McNaughton is always the first to arrive.) Today the team was assembled to hear a presentation by Rafaela Lone, a Brazilian scientist, who had spent the past six months in McNaughton’s lab breeding mice with symptoms that mimic fibromyalgia, a long-term condition that causes widespread pain and chronic fatigue. Lone explained that her mother had suffered from fibromyalgia for seven years. Her life had been reduced to a misery of symptoms ranging from urinary-tract infections to intense sensitivity to cold. Some days were bear-able; on others she couldn’t get out of bed. “She learns how to hold the pain,” said Lone.

McNaughton looked aggrieved at this (he finds it so hard to tolerate other people’s discomfort that, when his grandchildren come to stay, he lets them sleep in his bed because he can’t bear to disappoint them). But there was hope. Lone’s slides revealed her preliminary findings. Using genetic and pharmacological methods based on McNaughton’s research, she had achieved a consistent eradication of the mice’s pain. McNaughton looked exultant: “It’s really worked spectacularly well, hasn’t it?”

His eureka moment occurred back in 2010. From previous research, he knew that a group of ion channels (protein molecules that span a cell’s membrane), known as the HCN family, modulated pain sensation. When a nerve is stimulated, a message is sent via the spinal cord to the brain, which then interprets it as pain. The challenge was to find the right ion channel to target with a drug. His team slowly worked their way through the group: blocking HCN1 had little effect and they didn’t want to interfere with HCN4 as it regulates the heart rate. Then they tried HCN2.

The team bred genetically engineered mice from embryos that had HCN2 excised from their DNA. Subsequent experiments showed that these mice did not develop neuropathic pain (the kind that affects the nervous system and is often caused by long-term conditions such as cancer or diabetes). Not only that, the mice with HCN2 cut out were still able to feel acute pain – the necessary, protective jolt that tells us to remove our finger from a drawing pin. “That’s the holy grail,” McNaughton told me, sitting in his modest office in his lab, pictures of his family looping on his computer screensaver. “It is! It really is!” (On the mice in question, McNaughton was remorseful: “I’m acutely aware that this is unpleasant for the mice,” he said.)

After his discovery, McNaughton’s research group developed chemical compounds able to achieve, by blocking the HCN2 ion channel, the same effect in mice as the genetic technique. These form the basis for a prospective painkilling drug with the potential to treat multiple chronic-pain conditions (further research has shown strong evidence that blocking HCN2 has a positive effect on mice mimicking symptoms of rheumatoid arthritis and migraine).

McNaughton filed three patents, pitched his research around the large pharmaceutical companies and a deal was then reached earlier this year between King’s College London and the Wellcome Trust (who helped fund the research) and Merck, an American pharmaceutical giant (known as MSD outside America and Canada). The deal is worth $340m plus royalties if the drug comes to market. That may sound like a large sum, but it is nothing compared with the profits that Merck could reap, in an industry where the larger the potential patient pool, the greater the reward. Chronic pain is estimated to affect a fifth of the global population, or 1.5bn people. “It’s an absolutely vast market,” said McNaughton.

The windfall would not touch McNaughton himself. “Do I need a helicopter? Do I need a house in Mustique?” he asked happily. “The answer is no.” Instead, if his drug survives Merck’s rigorous clinical trials, he will be content that he has helped people like the elderly woman in rural Canada who recently wrote to him pleading for assistance in a life blighted by pain caused by type-2 diabetes. Her suffering made no sense to him. What was its purpose? Think how much happier we would all be without pain, how productive, how hopeful. Here, surely, was a problem like any other scientific problem, one that must logically have a solution. “Give them a pill that makes the pain go away and then their life blooms once more!” he said, delighted by the thought. “Do you think that’s over-optimistic?”

We need pain, even if we don’t want it. Acute pain – the finger on the pin – is a defence against danger, our brain’s way of telling us to react to something that’s wrong. The rare, poor souls who suffer from congenital insensitivity to pain have a reduced life expectancy, the cumulative effect of multiple injuries and burns from infancy onwards. Pain is the natural early-warning system that keeps us alive.

But the purpose of chronic pain, which scientists define as pain that lasts for more than three months after its initial cause, is more mysterious. The pain’s origin might be muscular-skeletal – the result of a fall, perhaps – or neuropathic, caused by damage to the nervous system. Or it might be a result of a long-term condition, such as fibromyalgia. Whichever way, it is a pain that has gone on beyond its expected life span and does not respond to medication. Often it is a discomfort that has become invisible and shifted shape, growing harder to understand the greater the distance from its original cause. A physiotherapist suggested to me that chronic pain was like a musician being given a piece of sheet music to play. The musician learns the music and when the music is taken away, she continues to play it. The body has learned the pain by heart.

Our instinct when in any kind of pain, acute or chronic, is to make it stop. We reach for drugs, typically one of two groups: anti-inflammatories such as aspirin and ibuprofen, or opioids. Both types of drug are blunt, ancient instruments that have been around in various forms for thousands of years, a fact that would be quaint if the pills weren’t also potentially lethal. Aspirin derives from willow bark, whose first-recorded use as a painkiller was in Egypt in 1500BC. The opium poppy is known to have been cultivated in Mesopotamia in 3400BC (the Sumerians apparently called it the “joy plant”) and opium was recommended before surgery from at least as early as the second century AD, when the Greek philosopher Celsus recorded its use as an anaesthetic.

Though these drugs are cheap and effective at dealing with acute pain, prolonged use can lead to problems. Multiple studies have shown that anti-inflammatories increase the risk of heart disease and stroke. A paper from 2017 by researchers in Denmark found that standard prescriptions of ibuprofen were associated with a 31% increased risk of cardiac arrest. This prompted calls for over-the-counter sales of the drug to be restricted.

Opioids, meanwhile, are so addictive they can make people dependent within weeks and kill them within months. The unfolding catastrophe in America shows how great our desire is to medicate chronic pain: opioids have become a blight on whole regions. At the peak of the crisis in 2017 in Huntington, West Virginia, deaths from drug overdoses stood at ten times the national average. Over the past 20 years, the drugs have caused the deaths of an estimated 430,000 people and turned plenty more to heroin once their prescriptions ran out. When Oklahoma’s attorney-general brought one of hundreds of state lawsuits against the multiple drug companies involved, he described the situation as the worst man-made public-health crisis in American history.

The opioid crisis has intensified the race among pharmaceutical companies to find a new, safe, targeted painkiller. (In August, pain researchers were excited by the discovery that subcutaneous cells known as Schwann cells play a role in the transmission of pain.) Phil L’Huillier, Merck’s head of business development in Europe and the man who brokered the deal with McNaughton and King’s, told me he’d been actively looking for “pain opportunities” since he joined the company two years ago. L’Huillier is a well-ironed executive with the fluid, even tones of someone who gives frequent PowerPoint presentations. As he led me through Merck’s London offices, we passed a lobby adorned with huge images of smiling African and Indian children whose lives have been transformed by the company’s drugs.

When it comes to pain, Merck’s history is less poster-friendly. In 2004, five years after Vioxx, its new selective anti-inflammatory painkiller, had been approved by the US Food and Drug Administration, Merck was forced to withdraw it after studies showed that long-term use was associated with an increased risk of heart disease. (One paper estimated the drug might have caused up to 139,000 heart attacks while it was available.) By 2006, 190 class-action lawsuits had been filed against Merck and the following year the company agreed to a settlement of $4.85bn to cover 27,000 individual cases in America alone.

L’Huillier didn’t want to dwell on the Vioxx scandal when we met. “It’s a long time before my time,” he said. Instead he was keen to emphasise that Merck is committed to “developing really good molecules”. He knows the race is on: drug companies across the world are combing through scientific research to find the next painkiller, the one that won’t spawn a generation of addicts. L’Hui-llier admitted McNaughton’s research wasn’t the only opportunity he was pursuing: “You have to have more than one shot on goal.” Often research that looks tantalising on paper or when tested on mice doesn’t work in the same way on humans. Translation from the controlled environment of the laboratory to the unpredictability of real life is notoriously hard, humans being both fickle in their responses to medication, and not identical to mice.

L’Huillier was excited by the enormous potential of McNaughton’s work. Teams of Merck scientists were now finessing McNaughton’s compound before selecting the two that had performed best on mice – what they call a lead and a back-up molecule. These would then be put through three phases of clinical trials. Ideally, the drug would become what L’Huillier called a broad-spectrum painkiller: one that could safely be used to treat multiple chronic-pain conditions.

To reach this point the drug would have to succeed where so many have failed. Pain medication faces distinctive problems that don’t apply to other drugs. Unlike cancer, for example, pain doesn’t have clear biomarkers: you can’t measure the effect of a drug that treats it by counting white blood cells. Instead, researchers rely on patients giving their pain a score on numbered scales, from one to ten, say, or on a visual scale, where the individual marks the level of their pain at a point on a line between two extremes. But pain is infuriatingly subjective. The placebo effect is significant: give someone a sugar pill and they’ll report an improvement in their pain just because it has been noticed and apparently treated. There is no way of knowing if one person’s report of their pain means the same as another’s. “Your nine is different to my nine,” said L’Huillier, who looked somewhat despairing at the thought of such a crude measure being used to determine the efficacy of a drug in which his company had just invested hundreds of millions of dollars. “I have no idea what your nine is versus my nine. And that’s what we’re using in trials.”

The worst pain I’ve ever experienced – I write this with some embarrassment – was a fairly mild lower backache that seemed to take up permanent residence in my body during my early 20s. I’ve since given birth twice, once after a 48-hour labour and an epidural that didn’t work, and once with no pain relief (and everything tore). But the backache was worse. The pain of childbirth is deranged in its intensity and I remember, as a nice nurse sewed me up, shaking, weeping and vowing never to let anything travel from my womb to the outside world again. I couldn’t articulate the pain afterwards. I still can’t. All I can recall is the noise I emitted as my baby came out, a sort of baritone roar I’d never heard before and hope never to again. But at least the pain of childbirth has a purpose. It ends relatively quickly and is offset by a surge of helpful hormones, such as oxytocin. You heal, you have a baby that needs looking after, and you forget (sort of).

The backache, by contrast, went on for months, even years. It was near-constant when I was sitting at a computer and meant that I spent hours every day at work distracted and mildly irritated. Also, it didn’t sound that bad and you couldn’t see it, so it was hard to make others sympathise. Everyone has backache, for goodness sake. The pain didn’t feel urgent or legitimate. I couldn’t go on talking about it: there was nothing to say, and nothing, it seemed, to do. I saw the same expression pass over the faces of GPs, physiotherapists and osteopaths as they thought, “oh, one of them, the untreatable lower-back-pain brigade.” I’d always thought that pain was measured by intensity: that the worst was the sharpest. But it struck me that an intense, brief pain was probably preferable to a duller one with no end in sight. The way you think about pain, it turns out, can be as painful as the sensation itself.

Despite advances in brain imaging and rapidly expanding biological knowledge, there is still much about pain that we don’t fully grasp. “We haven’t really understood what pain is,” admitted Jane Ballantyne, a professor at the University of Washington and one of the world’s leading pain researchers, in a recent interview on the Pain Research Forum’s website. “We have this disconnect between nociception” – our sensory response to harmful stimuli – “and what we feel as pain.” In other words, we have not yet fathomed the gap between the physiological responses to pain and the mental experience of it.

We know, at least, that pain is relative: my daughter stubs her toe and the agony is entirely real and catastrophic because it is the worst pain she has known in her five years alive. Though I can empathise, I can’t truly understand what her pain feels like: it’s simultaneously as close and as distant to me as her thoughts. Similarly, I have no idea if my friend’s experience of the pain of childbirth was anything like mine, even though we both ended up with a baby. Beyond generalities, our experiences are entirely singular. “When one hears about another person’s physical pain,” writes the American writer Elaine Scarry in her book, “The Body in Pain”, “the events happening within the interior of that person’s body may seem to have the remote character of some deep subterranean fact.”

All we can rely on is the way a sufferer describes her pain. Language often falls down in these moments: how do you put words to an invisible, internal sensation? “It was a pain unlike anything I’d ever felt,” Rafaela Lone’s mother wrote to me in an email about the pain of her fibromyalgia. Cold water felt like needle pricks on her skin, she said. On online fibromyalgia forums, I read countless accounts of symptoms. The sufferers – almost all women – tended to reach for similes to make the intangible seem solid. “It feels as if someone is twisting the upper and lower ends of my limbs in opposite directions,” wrote Julia. “It feels like I’ve been in a massive car accident and should be bruised, broken and bleeding, but I look in the mirror and I look fine,” replied Kathleen.

You can almost detect a wistfulness. It would be easier to be covered in blood and bruises than suffer from a pain with no visible cause. It often takes people a long time to receive a diagnosis of fibromyalgia: its symptoms are poorly understood and inconstant. Women are nine times more likely to have the condition than men and sufferers often report that they encounter suspicion from male clinicians who wonder if their account of fluctuating pain and profound fatigue is simply a version of anxiety (also far more common among women than men). This can be compounded by the fact that fibromyalgia is sometimes triggered by stress or a traumatic event. Lone told me that her mother started having symptoms after the suicide of her brother. Emotional anguish was at the root of her fibromyalgia, but that didn’t negate its bodily reality: the two were now working in delicate and distressing harmony. Once pain takes up long-term residence in both body and mind, it can be hard to dislodge. The usual approach – to quell it with drugs – stops working. The longer it goes on the harder it becomes to say precisely where the pain had started, or to see how it might end.

On a fibromyalgia Facebook forum, a place where sufferers gather to compare notes about morphing symptoms, I found Louise. When we spoke, she told me that her pain story had two beginnings. One was physical, when she hurt her arm two years ago after falling down some stairs at home while carrying a washing basket. The other was emotional, when she divorced her husband four years before that. Both, she felt, had played a part in the development of her condition.

After her fall, Louise was referred to a specialist who found nerve damage in her arm. She had three operations and a sympathy-inducing cast. But then the pain got worse and spread to her back. She went to another specialist to have a spinal-cord implant. An MRI scan showed she had a herniated disc. The pain continued to spread. It became so all-encompassing, from arm to back to entire body, that Louise started to struggle at work. She wondered if the pain was partly caused by stress. She worked for a large IT firm, travelled frequently and had recently been promoted. She spoke to a manager who said he understood because he’d had toothache last week. This was nothing like toothache, she wanted to say. Nothing at all.

Soon, Louise was taking a mix of painkillers. One caused bruising as a side-effect. When she discovered bruises all over her legs she went to her GP. He told her he couldn’t see anything, suggested her problem might be psychological, asked if she felt depressed and handed her a leaflet for counselling. Louise felt ashamed, as though she’d imagined it all. She carried on at work, hoping the pain would pass. Her body kept going until her mind gave way. On a Tuesday in January, when she could no longer walk in a straight line or hear anything her colleagues were saying, Louise stood in the middle of her office and assumed she was having a nervous breakdown.

At this point, Louise realised she couldn’t carry on. She changed GP and was signed off from work. She saw a rheumatologist, received a diagnosis of fibromyalgia and started taking about 15 different pills a day. She was also referred for cognitive behavioural therapy. Though she knew her physical pain was acutely real, she also knew that her experience of its symptoms was entwined with her emotional life. “I’ve noticed when I get upset and stressed about something I start shaking,” Louise told me. “The pain gets really extreme.” To solve her pain, or at least to understand it, she knew she would have to change the way she lived. And to do that, she knew she would have to change the way she thought.

Now, Louise makes a judgment each day about what her body will allow her to do and what her mind can tolerate. Flare-ups can render her immobile for several days, but she tries not to overreact in a way that will magnify the stress. She knows that if she goes out to dinner with her partner, she will need to rest the next day. She has been off work for six months, but hopes to return part-time when she can. She’s worried about money – recently, her application for disability benefit was rejected after an assessment that she found, in itself, traumatic and exhausting. Financial worries make her emotionally volatile, as does all the time spent at home alone. She has become more sensitive to how people treat her. Trivial things, such as someone being curt on the phone, can upset her hugely and trigger her symptoms. The cycle continues.

Sometimes Louise slips into understandable sadness. “I was in a really good position,” she told me of her life before pain. “Why now? Why me?” But then she will try to pull herself back, and think that perhaps these things happen for a reason. Perhaps the pain is the body’s way of telling the mind that something needs to change. “Maybe it was to make me step back and think about what matters.” She takes little for granted now. And with the help of her partner, she tries hard to remain positive. Every morning he asks her how her earlobes feel, because that is one of the few places in her body where she has never felt pain. At night, when she can’t get to sleep because her left leg hurts, she thinks about her right leg instead, and how lucky she is to feel no discomfort there.

Many people with chronic pain have had that moment in a doctor’s office: when they are told that it is all in their head, when they feel their sanity is doubted. A referral for psychiatric treatment can be galling if you believe you are suffering from a purely physical condition. Often patients bounce from doctor to doctor, hoping for clarity and ending up with ever more prescriptions. At this point, when they’ve bounced just about as far as they can, they might end up at the door of Dr Parashar Ramanuj, a consultant psychiatrist at the Royal Northern Orthopaedic Hospital in London.

Ramanuj treats pain patients with the most protracted, entrenched conditions: those who might have found themselves dependent on drugs with very little improvement, or whose life has become arrested by pain whose origin is often no longer even detectable under the layers of medication-induced effects. He knows that when patients finally reach his office, they have probably passed through multiple layers of the medical system which has been confounded by their symptoms. His patients’ ambivalence towards further intervention can be obvious before he even meets them face to face. Ramanuj sends all new patients three questionnaires covering their physical and psychological histories. Many don’t complete them and a significant minority don’t answer a single question. “But to a psychodynamic psychiatrist”, said Ramanuj, “that is information in itself.” Ramanuj will then try to fathom why his patient is reluctant to engage.

In person, Ramanuj is reassuring, lucid and calm, the kind of doctor who makes you feel like the world in all its chaos could be organised into rows. His understanding of pain is almost the precise opposite of Peter McNaughton’s. Pain, he believes, cannot be located in a molecule or a cell. It is not a peripheral phenomenon that exists at the edges of our bodies. While it might be caused by a physical event, pain is felt and lives on in the mind. In Ramanuj’s conception, a person’s experience of pain is shaped by their experience of life: their personality, their environment, their family, their social class. This is known as the “biopsychosocial” model, pioneered in the United States in the 1960s and 1970s.

Bill Fordyce, an American psychologist, established the first multi-disciplinary pain programme at the University of Washington in 1961. This serves as a model for most specialist pain services successfully treating chronic pain patients today. It treats patients with a combination of physical, pharmacological and psychological therapies.

When Ramanuj meets a patient in person, he asks them for a history of their physical pain. “The first thing I need to do”, he told me, “is validate their experience.” Then he explores their psychiatric history to identify any obvious psychological disorders. Many of his patients have experienced significant emotional trauma (people who have had damaging childhood experiences are twice as likely to develop chronic pain). “Some of my patients have horrific stories to tell,” he said. “It is often painful for me just to hear them; it must be unimaginable to have lived through them.” The last half hour is spent going through what he calls theory testing – he tries out his interpretation of the person in order to come up with a shared understanding of their experience, explaining to them, for example, that their physical pain might be drawing their attention away from an emotional pain that is harder to confront.

Often Ramanuj hopes to have moved his patients from a position of sceptical resistance to a place where they can engage with the idea that their physical pain is entwined with their mental health. He explains theories about chronic pain to his patients, highlighting the biological similarities between how anxiety and pain are perceived. Finally, he suggests various treatments, usually a combination of non-addictive medication, psychological therapy and physiotherapy. The last thing Ramanuj typically tells his patients is that it’s absolutely true their pain is in their head. “If I cut you, the nerves go to the brain – that’s where you feel it. It is in your head,” he explained. After an hour and a half in his company, he hopes the notion might no longer seem so shameful.

At the British Pain Society’s annual scientific meeting – a late-spring jamboree at the Tower Bridge Hilton – Ramanuj gave a talk about the effects and side-effects of pain medications. In a windowless conference room, he asked how many of the attendees were anaesthetists. Almost everyone raised a hand – the room was full of people equipped with the power to erase pain completely. Ramanuj gave a jaded nod, and a little later showed a slide of a Venn diagram. “People with mental illness” was written in the loop to the left and “people in chronic pain” was written in the loop to the right. The overlapping middle section contained a statistic: 60-75%. Ramanuj sighed. “And yet I’m one of only two psychiatrists here.”

Outside the conference room were rows of stalls advertising pain-relieving gizmos to attendees as they drank their break-time tea. On one, a huge picture of a serene mother holding a newborn baby was positioned next to a display of epidural catheters. “Wireless pain relief” and “Freedom stimulators” were on show at the stall next door. “Qutenza®”, a capsaicin patch, in which chilli-pepper extract is used to soothe neuropathic pain, was advertised with a huge poster-sized image of a middle-aged woman in jaunty glasses, curled blonde hair and dark red nails sipping cheerily from a large mug. “Like your patients, we’re different”, read the tagline. To the pharmaceutical industry, this woman was clearly as zany as they come. Or perhaps, once pain-free, we women always put ringlets in our hair and paint our nails.

After his talk, Ramanuj retreated to the balcony of a nearby pub overlooking the Thames. He drank a pint of beer and had the unbuttoned air of a professional released into the wild. If your days are spent treating patients suffering from the most insoluble chronic conditions, a pain conference can feel like a holiday. When we’d spoken previously, I’d mentioned Peter McNaughton and his dream of a drug capable of eradicating chronic pain. “I’m sceptical about magic pills,” Ramanuj had replied. He listed a few so-called magic pills – valium, morphine – that had not lived up to their promise. “They’ve not just fallen out of favour, they’ve fallen out of grace.” That is, they’ve become morally dubious, capable of more harm than good if improperly prescribed or abused. When I put to him the theory that a truly effective painkiller might also be able to cure a chronic-pain patient’s depression, he shook his head. “There are so many theories as to why that would not happen at all,” he said. “The physical pain may actually be keeping the emotional pain at bay.”

Ramanuj pointed to plentiful research that shows how physical and emotional pain fire up the same regions of the brain. One pain can mask the other; it is far easier, after all, to confront a physical affliction than an emotional wound. Even if there were some kind of miracle cure, you would still need to contend with the vagaries of human behaviour. Patients regularly choose not to take drugs that might help them; sometimes, they seem not to want to get better. The lives of people in entrenched chronic pain have often unravelled: they might have lost jobs or relationships, years of productive existence. We all need a story to tell about our lives, to explain why we are where we are. For some, pain has become the explanation. “Pain occupies so much of your mind, you’re hardwired to attend to it; that’s what its purpose is,” said Ramanuj. “When you’re attending to physical pain there are other things you don’t need to attend to.”

For a scientist like McNaughton, who believes in the reassuring logic of causality, the notion that chronic pain might be so bound up with a person’s psychology that it can’t be eradicated by a well-designed drug strikes him as “deeply pessimistic”. The last time we met, in a café outside the 7th International Congress on Neuropathic Pain (in yet another London Hilton), he’d just been listening to a presentation about why so little scientific research into the phenomenon had ever been translated into successful drugs. The tone of the talk, he felt, had been typically negative. Recently, he’d had a dispiriting conversation with one researcher at Merck. When he suggested that his drug might be the game-changer they were all waiting for, she’d scoffed and told him it was impossible. In her entire professional life, she’d never observed anything like that happening. No drug changes the world overnight.

McNaughton refused to be discouraged. As we spoke, he happened to be sitting beneath a large circular pendant light that made him look as if he was wearing a halo. It suited his undimmed faith. “Sometimes people in the field laugh at us,” he told me. “They say, ‘People have been trying for many tens of years to solve these problems and no one has been successful. Why do you think you’re going to be?’” Such doubt makes him furious, as furious as the world’s most optimistic man can ever be. “How can they be so arrogant and so puffed up with themselves to suggest that? There are many problems in the past that appeared absolutely intractable, medical problems, and then we have solutions.”

He’s right. The history of medical science is full of breakthroughs that at one point seemed impossible. Look at penicillin or HIV medication. If the consequences of infections and AIDS could be dramatically mitigated, why can’t the same thing happen to pain? We are drawn to the idea of being fixed: the “fantasy of cure” as one psychologist described it to me. Hope is much more seductive than a shrugging acceptance of the human condition. We don’t want to be told our pain can’t be cured and that instead we have to change the way we think about it. We aspire to a life without discomfort, without unpleasantness. But what kind of life would that be? It is as hard to imagine a world without pain as a person without sadness: a whole dimension of existence would be missing.

Under his halo, McNaughton wondered whether he’d live to see his work come to fruition. He was nearing 70, but he’d always said he’d work until he was 95. Having just secured a multi-million-pound deal for his university, he wasn’t about to be shuffled off into retirement. If he could live for another ten years, he’d know if his drug would make it to market. Ten more after that, and he’d see whether it had successfully treated millions of people in chronic pain. These things take time, of course, but it all seemed entirely possible, in the best of all possible worlds. “Nobody believes me,” he laughed. “But you just wait.”■

Illustrations Noma Bar