Sufferers of chronic pain have long been told it’s all in their head. We now know that’s wrong

By Linda Geddes

It started with headaches and neck pain, but no sooner had Tricia Kalinowski’s physiotherapist come up with a strategy to tackle these problems, then another area of her body would start to hurt: her lower back, her hip or her jaw.

“The physio was chasing the pain up and down my body,” says Kalinowski, 60, from Minneapolis, US. Eventually, she was referred to an oral surgeon, who believed the root cause of these issues was a problem with one of the joints in her jaw, so she underwent surgery to replace a thumbnail-sized disc.

Unfortunately, the replacement was defective, triggering an immune reaction that resulted in the loss of several inches of jawbone. It took 13 rounds of surgery to fix the damage – the last of which was performed in 2015. “The irony to all the surgeries is that I still have headaches, I still have neck pain, and nobody really knows quite what to do about it,” she says.

Tricia Kalinowski
Tricia Kalinowski suffers from chronic pain. Photograph: Nina Robinson

To most people, pain is an unpleasant but short-lived sensation, occurring as a result of illness or injury. Although some people may experience ongoing or chronic pain, the assumption is there must be some kind of underlying physical injury, such as a crushed nerve, or an angry, inflamed joint.

Increasingly though, experts are waking up to the idea that chronic pain can occur without any obvious physical injury, or in a completely separate area of the body from the original site of tissue damage. There’s also mounting evidence that seemingly very different pain conditions – chronic headaches, low back pain and jaw pain, say – may share common underlying mechanisms, and that once a person develops one chronic pain condition, they’re predisposed to develop others.

The Covid-19 pandemic could make this situation even worse. One of the most common symptoms reported by people with “long Covid” is musculoskeletal pain, and those with existing musculoskeletal pain conditions seem to be at risk of experiencing stronger pain after a serious Covid infection.

“Musculoskeletal pain is an issue that we must start considering as a long Covid problem,” says Prof Lars Arendt-Nielsen, immediate past president of the International Association for the Study of Pain (IASP) and director of the world’s largest translational pain research centre at Aalborg University in Denmark.

The health profession as a whole does not treat people with chronic pain well. And it is about to be hit by a tsunami of severely ill people needing help.

‘Reorganisation of the pain system’

Pain probably evolved as a means of identifying potentially harmful stimuli and withdrawing from them, as well as teaching us to avoid these things in the future. It can also help to protect injured body parts while they heal. But when it continues beyond this recovery period, it has lost this useful function. Chronic pain is a leading cause of disability, affecting about 20% of people globally, but more than two-fifths of people in some countries, including the UK, and is predicted to increase as populations age.

Traditionally, doctors have divided pain into two categories: nociceptive pain, triggered by injuries such as bruises, burns, fractures, sprains or inflammatory conditions such as arthritis, and detected by pain receptors in our skin, bones and other tissues; and neuropathic pain triggered by damage to the nerves that carry sensory signals from these tissues to the brain and spinal cord.

But a few years ago, the IASP introduced a third category: nociplastic pain – pain arising from the altered processing of these sensory signals, without any evidence of actual or threatened tissue damage. One thing that can happen is that the pain signals carried by peripheral nerves from the skin, muscles, joints or internal organs to the spinal cord can become amplified, worsening the pain.

Prolonged activation of the body’s pain pathways can also lead to changes in the brain and spinal cord. According to the old way of thinking, the body’s pain pathways were arranged like a telephone switchboard, with fixed sets of wires (nerves) connecting our peripheral organs and tissues to the spinal cord, and further nerves connecting the spinal cord to the brain as well as feeding back down in the opposite direction.

“The assumption was that this was a fixed, solid, stable system,” Arendt-Nielsen says. “But we now know that these neural networks can be reorganised when there are persistent inputs into the system, and cause increased gain of the pain signal and hence generate a stronger pain.”

What is chronic pain and how does it work? – video explainer
What is chronic pain and how does it work? – video explainer

For one thing, nerves in the brain and spinal cord – the central nervous system – can become hyper-excitable, meaning that minor bumps and grazes become agonising, and even non-painful stimuli such as brushing your hair or touching your skin can trigger pain. “It is like an allergic reaction in the pain system,” Arendt-Nielsen says.

This “central sensitisation” can also spread. “One of the features that we see in many patients with chronic pain is that they have this generalised pain hypersensitivity. They might have osteoarthritis and pain in their knee, but if you quantitatively assess the sensitivity of the pain system, they have a lower lower pain threshold throughout their bodies,” Arendt-Nielsen says. “This reorganisation of the pain system is the reason why management of chronic pain is difficult, and traditional analgesics are not efficient – and why pain research is so important to discover new ways to modulate this pain reorganisation.”

It may also help explain why so many people with chronic pain conditions subsequently develop more of them. More than 200 million people around the world are affected by chronic overlapping pain conditions – a cluster of painful disorders which often coexist in the same patient.

“Over the past 10 years, there’s been the widespread recognition that pain can be a disease in and of itself, and a growing understanding that it is a multi-system illness, and that there are shared mechanisms of disease across these conditions,” says Christin Veasley co-founder and director of the US-based Chronic Pain Research Alliance.

A patient like Tricia Kalinowski may start out with jaw pain, then gradually accumulate other conditions, such as fibromyalgia, endometriosis, migraine or irritable bowel syndrome, as time wears on. Other related conditions include temporomandibular disorder (pain related to the jaw joints), painful bladder syndrome, vulvodynia (pain around the opening of the vagina), chronic low back pain and tension-type headache.

“In many people with conditions like low back pain, endometriosis, irritable bowel, headache, fibromyalgia, you’re not going to find a problem in the area of the body where the person is experiencing pain. There’s more and more evidence that these are central nervous system, systemic conditions, where the pain can present in different areas of the body at different points in time over that person’s life,” says Daniel Clauw, a professor of anesthesiology, medicine and psychiatry at the University of Michigan.

He likens the experience of pain to the noise produced by an electric guitar; to make it louder, you can either strum the strings harder or turn up the amplifier. In this analogy, the strings are represented by the peripheral nerves carrying sensory information from our organs and tissues, and the amplifier by the brain and spinal cord.

Color CAT scan of the lateral skull
A Cat scan of the lateral skull. Prolonged activation of the body’s pain pathways can lead to changes in the brain and spinal cord. Photograph: John Greim/LightRocket/Getty Images

A patient with third-degree burns is having their strings strummed extremely hard, whereas in someone with fibromyalgia – a long-term condition that causes pain all over the body – their amplifier has been set too loud. “They can have pain, without the strings even having to be strummed,” Clauw says.

Central sensitisation is one way of turning up that amplifier. It can be triggered by intense, repeated and sustained activation of the nerves that carry pain signals – as a result of a major injury or prolonged infection, say.

People’s innate amplifier settings can also vary. Not everyone who develops a chronic pain condition will develop more of them but they seem to be particularly prevalent among women, and those affected also often suffer from non-pain conditions such as sleep and mood disorders, and fatigue.

Some of this variation between men and women may be due to immune system differences, with women also more prone to autoimmune disease. Immune cells trigger inflammation, which can trigger pain. Sex hormones such as oestrogen and testosterone can further exacerbate or dull pain, depending where they are released and in what quantities.

Laid on top of those basic amplifier settings are events that happen to you as you go through life. Chronic pain is more common among people who experienced lots of surgery as children, or emotional or physical abuse. There is also a strong link between chronic pain and depression. Of course, living with chronic pain can be depressing, but depression can also amplify pain processing in and of itself.

This is not the same thing as suggesting that someone’s mental attitude can affect their pain. “Rather, people often don’t realise that the brain pathways that drive depression are intrinsically linked to the ones that drive chronic pain,” says Dr Kirsty Bannister, a senior lecturer at King’s College London, who researches these pain pathways.

When pain signals arrive in the brain, they are transmitted to areas that allow us to locate and categorise that pain, as well as to areas that process emotions. These brain areas then send signals back down the spinal cord, which, in health, causes those original pain signals to be dampened. This is why your thumb begins to stop hurting several minutes after you’ve bashed it with a hammer.

But in people with a history of depression or childhood trauma, those emotion processing areas are often wired differently, which can alter the type of signals they send. As a result, their pain pathways carry on being activated. “Because our life experiences are not equal, it means that previous issues such as fear, hopelessness or helplessness may escalate your pain to a very different intensity compared to mine,” Bannister says.

That’s not to say that everyone with chronic pain is affected by this problem of nociplastic pain or central sensitisation. “Fibromyalgia is the poster child for it, but you see elements of fibromyalgia in other conditions, such as low back pain,” Clauw says. “Probably 40 to 50% of people with low back pain really have something a lot more like fibromyalgia than a problem in their back, and 70 to 80% of people with bladder pain syndrome really have more of a fibromyalgia phenotype, where they have pain in their bladder, but they have pain elsewhere as well.

“What we think happens in these post-infection, post-motor-vehicle accident kind of syndromes is that everyone has this background degree of ‘fibromyalgia-ness’. And then this gets blasted open by getting Covid, or being in a hospital where you sleep terribly and you’re inactive for weeks or months. Whatever you were doing in your life that was sort of keeping that all that bay comes crashing down.”

Covid as trigger

Vicky Naylor, 55, a nurse from Wigan, in the UK, developed fibromyalgia after undergoing an emergency C-section 11 years ago, but through a combination of swimming, yoga and medication, had her symptoms under control. “It was only if I had an illness or got very stressed that I’d get flare-ups. I’d become very stiff, and get painful joints and trigger points [tender spots around the body] and headaches, but I could always get them back under control and deal with them,” she says. “I never missed a day’s work.”

Then, in March 2020, she developed Covid-19. Her initial symptoms were severe –fever, shortness of breath and a cough so bad she lost her voice – although she was never admitted to hospital. But as the weeks turned to months, she began to experience a plethora of other symptoms, including excruciating pain. “It is off the scale,” she says. “I get it in my feet – some days it is so bad I can’t bear to wear filled-in shoes. I get it in my knees, the tops of my legs, my right hip particularly, my elbows, shoulders, neck – it’s just everywhere.”

Naylor isn’t the only person who is experiencing ongoing pain after developing Covid-19. In a study, Arendt-Nielsen, together with Prof César Fernández De Las Peñas at Rey Juan Carlos University in Madrid and colleagues, assessed more than 1,100 people who had been hospitalised with the virus seven months after they first developed symptoms.

“We found that approximately 70% developed two to three persistent symptoms, and of those 40% developed musculoskeletal-related pain,” he says. “Also, if you had musculoskeletal pain problems prior to your infection, then seven months later, there was a big chance that you would experience stronger musculoskeletal pain. Those patients with musculoskeletal pain problems prior to the infection were also more likely to have myalgia (muscle pain) during the hospitalisation.

“So far we do not know for how long the post-Covid conditions will last. As chronic pain already globally affects approximately one out of five adults, we hope that the Covid condition will not add to this global burden as there are already many bottlenecks to overcome for this vulnerable chronic pain population when they seek optimal management.”

In a separate study, neurologists at the Vall d’Hebron University hospital in Barcelona discovered that almost two-fifths of the Covid patients they assessed in the accident and emergency department were still experiencing “persistent and disabling daily headaches” six weeks later.

Covid might be triggering chronic pain through various mechanisms. Lingering inflammation triggered by the immune system’s response to the virus could be stimulating pain receptors in various tissues. “Immune cells make things that the nerves don’t like, and so the nerves could become sensitised,” says Dr Franziska Denk, a pain researcher at King’s College London.

The Ace2 receptor that Sars-CoV-2 binds to is also expressed in sensory neurons. “That’s bad news, because it could be that, like many other viruses, it can damage the sensory neurons,” Denk says.

In some people, this nerve or tissue damage will be their only source of pain. “There’s going to be a lot of people that have nociplastic pain superimposed upon that,” says Clauw.

‘A trial and error experiment’

Unfortunately, our health systems are ill equipped to deal with chronic pain – and particularly patients with chronic overlapping pain conditions. Like many patients with chronic pain, Kalinowski takes multiple drugs to get through the day. Working out which ones work for her has taken years.

Tricia Kalinowski
Tricia Kalinowski takes multiple medications daily to cope with pain. Photograph: Nina Robinson

“A lot of people describe it as trying to navigate a maze,” Veasley says. “It is this hit-and-miss, trial-and-error experiment of trying to firstly find someone who’s knowledgeable about even one of these conditions, much less their overlap or interconnectedness. Even then, we really have no idea what treatments or therapies work for which patients.”

Although pain experts have accepted the existence of central sensitisation, family doctors are less aware of it, meaning they may dismiss a patient’s pain in the absence of any obvious abnormality or injury. “I find it terrifying to think that anyone who has been to their GP to complain about pain has been sent on their way,” Bannister says.

Nor is there any widely available test that doctors could use to determine if someone’s pain is the result of central sensitisation or not. “There is no biomarker that would allow an individual to turn around to their GP and say, ‘You know, this is proof that I’m not being hysterical or making it up,’” says Bannister.

One problem stemming from this poor medical appreciation of chronic pain is the overprescription of opioid drugs. Although opioids are effective at dampening short-term severe pain or cancer pain, they are highly addictive and accidental overdose kills about 50,000 people in the US alone each year.

They can also make chronic pain worse. This is because opioids provide relief by blocking pain receptors but your body responds by increasing the number of pain receptors, meaning you need higher doses to get the same relief. In chronic pain conditions such as fibromyalgia, people have already been producing natural opioids called endorphins, which bind to the same receptors. “Giving them an opioid is like throwing kerosene on to a fire,” Clauw says.

The good news is that attitudes to chronic pain are changing, even if it may take the wider medical community a bit of time to catch up. In July 2020 the IASP updated its definition of pain to cover nociplastic pain – that arising in the absence of obvious injury. Pain is “an unpleasant sensory and emotional experience associated with, or resembling that associated with, actual or potential tissue damage”, it now says.

Alongside its revised definition, the IASP published a set of accompanying notes: “One of them was that a person’s experience of pain should be respected,” Bannister says. “Regardless whether you think that they don’t look like they’re in pain, or they’ve only had a cut to the foot, so how can they possibly be complaining, we have to respect a patient’s report of pain, and treat them as individuals.”

As for Kalinowski, if she could offer a single piece of advice to others in a similar situation, it would be to not give up, and seek an alternative medical opinion, if necessary: “You need to trust yourself, no matter what the doctor says, and keep pushing on until you find a doctor who does believe you – even if they can’t define what it is you have.”

Sufferers of chronic pain have long been told it’s all in their head. We now know that’s not true. The pain that can’t be seen is a week-long investigation looking at why doctors are playing catch-up on chronic pain conditions like endometriosis, migraine and more – and what they have to do with long Covid. In the next part, you can read about why women are more likely to have long Covid and chronic pain and hear from 10 readers on their experiences living with theses illnesses.