Why pain doesn’t measure damage, and why that doesn’t make it imaginary

Two people open spine MRI reports on the same afternoon. One hasn’t had back trouble in years, but the report lists disc degeneration and a bulge, and suddenly every twinge feels ominous. The other has hurt for months, and the report says little is wrong. Both walk away believing the same thing: the picture should match the pain.

It often doesn’t. A review of 33 imaging studies covering 3,110 people with no back pain found disc degeneration in 37% of 20-year-olds and 96% of 80-year-olds. At the other extreme, people born with both copies of a single gene disabled can break a bone and feel no pain.

The explanation is that pain is not a gauge wired straight to your tissues. Your nervous system produces it after weighing incoming danger signals against context, memory, attention and expectation. That idea is easy to mishear as it’s all in your head. Read correctly, it says something closer to the reverse: pain is a real event in a real nervous system, and that system can err in either direction.

Nociception is a signal, and pain is an experience

Your skin, muscles, joints and organs carry nociceptors, nerve endings that respond to heat, pressure or chemicals strong enough to threaten harm. The International Association for the Study of Pain (IASP), an international professional association devoted to pain, calls their work nociception: the nervous system encoding a harmful stimulus. Its glossary adds that nociception can raise blood pressure or trigger a withdrawal reflex, and that it does not necessarily come with the sensation of pain.

When the IASP revised its definition of pain in 2020, it put that distinction up front. Pain and nociception are separate phenomena, its notes say, and pain cannot be inferred from sensory-neuron activity alone. The notes also ask that a person’s report of pain be respected, and they say pain is shaped, by different amounts in different people, by biological, psychological and social factors.

The revision’s back story is telling. A 14-member IASP task force worked on it for nearly two years and posted a draft for public comment from August 7 to September 11, 2019. It drew 808 responses from 46 countries, and 42% came from people living with pain, people disabled by it, or their caregivers. The draft described pain as a subjective experience. Respondents warned that readers might take that word to mean not objective or even not real, so the final notes call pain a personal experience instead.

The task force made a second change for a similar reason. A draft phrase saying pain is typically caused by tissue injury was replaced with the older associated with, which, the task force explained, implies no direct cause and effect. Both edits push the same way, away from the idea that pain only counts when visible damage explains it.

Three places where damage and pain part ways

Scans of people who feel fine

The imaging review mentioned above, led by Mayo Clinic radiologists and published in 2015 in the American Journal of Neuroradiology, pooled studies of people with no back symptoms. Going from age 20 to age 80, the share whose scans showed each finding rose like this:

• Disc degeneration: 37% to 96%
• Disc bulge: 30% to 84%
• Disc protrusion: 29% to 43%
• Annular fissure (a small tear in the disc’s tough outer ring): 19% to 29%

The authors concluded that many of these features are probably part of normal aging and have nothing to do with pain. The IASP task force cited the same kind of mismatch in knee osteoarthritis, where how much a joint hurts and how damaged it looks on imaging can disagree.

Pain with no tissue to hurt

After an amputation, many people feel pain in the limb that is gone. A 2026 meta-analysis of 51 studies and 13,053 people with amputations put the pooled rate of phantom limb pain at 61%, though the studies varied so widely that the exact figure is rough. There is no tissue left in that limb to be damaged, yet the pain is real. Why the brain keeps producing it is still debated, a dispute laid out in our article on neuroplasticity.

Damage with no pain

In 2006 a Cambridge-led team reported in Nature on three families from the same clan in northern Pakistan whose affected members had never felt pain. Each family carried its own mutation disabling a gene called SCN9A, which encodes a key part of a sodium channel, Nav1.7, that is plentiful in pain-sensing neurons. The authors wrote that their data suggest this channel is essential for nociception in humans.

Life without that alarm is hazardous. According to MedlinePlus Genetics, from the National Library of Medicine, people with this inherited condition can still tell sharp from dull and hot from cold, but they may not notice that a drink is scalding their tongue. Many have no sense of smell. They tend to collect wounds, bruises and broken bones; unnoticed eye injuries can cost vision, long-lasting joint injuries can deform joints, and life expectancy may be shorter. The condition is rare, and its exact frequency is unknown.

The authors predicted their finding would spur a search for painkillers aimed at that channel. In January 2025 the Food and Drug Administration approved suzetrigine for moderate to severe acute pain in adults, the first drug in a new class that targets a pain-signaling pathway involving sodium channels in the peripheral nervous system, the nerves outside the brain and spinal cord. Its channel is a different one, Nav1.8. In two phase 3 trials after tummy-tuck and bunion surgery, with drugmaker employees among the authors, it beat placebo but did not outperform a hydrocodone and acetaminophen combination; pain relief was described as similar. The FDA lists itching, muscle spasms, raised creatine phosphokinase and rash among common side effects, and warns against combining it with strong CYP3A inhibitors or grapefruit. Whether it suits any one person is the prescriber’s call.

The volume controls between body and brain

In 1965 Ronald Melzack and Patrick Wall proposed in the journal Science that signals from thin, pain-related nerve fibers and thicker touch fibers meet at nerve cells in the spinal cord. The balance between those inputs, they argued, opens or closes a gate that decides how much reaches the brain, and pathways coming down from the brain can push on that gate too.

Later experiments showed the model was wrong in its details, as Lorne M. Mendell of Stony Brook University wrote in a 2014 retrospective. Its central idea survived and reshaped the field: pain signals are adjusted on their way up rather than delivered untouched.

A major adjuster sits in the brainstem. A 2007 review in Neuron co-written by Oxford pain researcher Irene Tracey described a descending network with two kinds of output, one that dampens incoming pain traffic and one that amplifies it, setting how much signal gets through for a given situation. A 2014 review from University of Arizona pharmacologists added that brain regions governing emotion, motivation and thinking talk directly to these circuits. It suggested that weakened descending inhibition may help decide whether pain becomes chronic, a hypothesis rather than a settled fact.

The National Institute of Neurological Disorders and Stroke (NINDS) makes a related point: the brain systems involved in pain overlap with those handling fear, anxiety and anger, reward and motivation, attention and memory. A 2013 review by a National Institutes of Health team went a step further, gathering evidence that long-lasting pain alters these control circuits and suggesting that pain becomes harder to turn down the longer it persists. When the system’s gain stays turned up, clinicians speak of central sensitization, which our next article takes apart.

Expectation and attention turn the dial

What you expect from a drug

A 2011 Oxford study in Science Translational Medicine infused healthy volunteers with a fixed concentration of remifentanil, a powerful opioid, during constant heat on the skin. What changed was their expectation: none at all, relief, or worsening pain. Expecting relief roughly doubled the drug’s pain-relieving effect. Expecting the pain to get worse wiped the benefit out. Brain scans tied the positive effect to the body’s own pain-modulating system and the negative one to the hippocampus, a memory region. These were volunteers under lab heat, not patients, but the lesson carries: the same dose of the same drug did very different things.

Placebo pain relief, briefly

Placebo relief runs on real biology, and more than one route. In a 1978 Lancet study of people recovering from wisdom-tooth surgery, naloxone, a drug that blocks opioid receptors, raised pain only in those who had responded to a placebo, which pointed to the body’s own opioids. A 2009 study in Science used spinal cord imaging to show that pain-related activity in the cord itself dropped under placebo, so belief can act at the first relay station. Yet a 2021 study at the National Center for Complementary and Integrative Health (NCCIH) of 32 people with fibromyalgia and 46 without found placebo relief in both groups that naloxone did not touch, and the authors credited learned association more than expectation. The wider science of placebo and its harmful twin, nocebo, is the focus of a separate piece in our library.

Where your attention goes

Most burn patients feel severe pain during wound care, and opioids alone often fall short, which made dressing changes an early test of distraction. The often-cited first report, from the University of Washington in 2000, described just two teenage boys. During immersive virtual reality (VR), one boy’s pain rating was 80 points lower, on a 100-point scale, than while he played a video game.

Trials came later. At Nationwide Children’s Hospital in Columbus, Ohio, a 2021 randomized trial of 90 children ages 6 to 17 found that those playing an interactive VR game reported average pain of 24.9 out of 100 during dressing changes, against 47.1 with standard care. Simply sitting inside the same virtual world without playing did not reduce worst pain the way the game did, which suggests engagement matters. A 2025 meta-analysis of 15 trials with 622 children found a large average reduction in pain, but the results varied so much from study to study that the average deserves caution. A stricter 2022 review that admitted only four randomized trials found that most results were not statistically significant.

On the library’s five-verdict scale, VR distraction during burn care sits in the tier of positive evidence whose interpretation is contested. No guideline we reviewed recommends it. Hypnosis and relaxation techniques, two other ways of redirecting the mind during pain, were weighed in earlier articles on each.

No scan can prove pain, yet

If pain is a brain output, why not read it from the brain? In a 2013 New England Journal of Medicine paper, a University of Colorado team used machine learning on brain scans from 114 people to build a neurologic signature of heat pain, a brain-wide activity pattern. It separated painful heat from mere warmth with sensitivity and specificity of 94% or more, and it weakened when volunteers received an opioid. But it was built on lab heat in healthy people, and the authors said further work was needed to learn whether it tracks clinical pain.

An IASP task force that included legal scholars took up the question in 2017 in Nature Reviews Neurology. It said brain imaging for chronic pain is still at the stage of discovery, set out standards of evidence any scan would have to meet before clinical or legal use, and concluded that using imaging to support or dispute someone’s claim of chronic pain, “effectively as a pain lie detector,” is not warranted.

A 2023 study shows how far away a routine test still is. A University of California, San Francisco team implanted electrodes in the brains of four people with hard-to-treat nerve pain and, over months, used machine learning to predict each person’s own pain scores from activity in the orbitofrontal cortex. That took brain surgery and worked one person at a time. For now, your account of your pain remains the measure.

Can learning how pain works ease it?

Pain neuroscience education (PNE) teaches people how pain works, much as this article does, aiming to make pain feel less threatening. The trials point to small effects, mostly short term, and the best results come when it is paired with exercise.

• On its own: A 2019 meta-analysis in The Journal of Pain pooled 12 trials with 755 adults with chronic musculoskeletal pain. Short-term pain fell by about 6 points on a 100-point scale, a difference that could have been chance and that the authors judged of low clinical relevance. Fear of movement dropped by a clinically relevant 13.55 points on a 100-point scale.
• Added to exercise: A 2022 meta-analysis in Pain of five trials with 460 people found about 2 points less pain on a 10-point scale in the 12 weeks after treatment than with exercise alone, on low-certainty evidence.
• The physical therapy guideline: The American Physical Therapy Association’s 2021 low back pain guideline says therapists should deliver PNE alongside other treatments such as exercise or manual therapy for chronic low back pain. That is its top tier of wording, which it links to grade A. It notes that studies using PNE alone found no pain improvement, while 5 of 6 studies combining it with another treatment did.
• The skeptical view: A 2025 review in The Journal of Manual & Manipulative Therapy accepted only prospectively registered, low-bias trials from 2010 to February 2025. Five qualified. It found no reliable evidence that adding PNE to a single physical therapy treatment improves pain or function, though it may build confidence and understanding and ease fear of movement.
• For new back pain: A 2019 Sydney trial in JAMA Neurology gave 202 people with recent low back pain, on top of usual first-line care, two hour-long education sessions or a sham version made of active listening. Pain at three months did not differ. A small benefit for disability appeared at one week and three months and was gone by six and twelve.

In the library’s terms, PNE is named in a guideline as an add-on for chronic low back pain, while for pain, PNE alone was measured but below the threshold that matters. Its most consistent effect is less fear of moving. If you have tried it alone and still hurt, the trials say you are typical, not failing. Where education fits among graded activity, psychological pain-management approaches and physical therapy is weighed treatment by treatment in the series that follows.

When a scan report alarms you

Radiology reports describe how tissue looks, in language written for doctors. A word like degeneration reads like a verdict on your future but often describes ordinary wear. Before a phrase on a report reshapes how you move or what you fear, these questions can help:

• How common is this finding in people my age who feel fine? For several spine findings, the pain-free numbers above are the baseline.
• Does it fit where and how I hurt? The Mayo-led reviewers were blunt: “These imaging findings must be interpreted in the context of the patient’s clinical condition.” That interpretation is a judgment for the clinician who examined you, not for the report alone.
• Did anything change the plan? Whether a finding calls for more tests, a specialist or another plan is the ordering clinician’s decision.
• Is a clean report being treated as proof the pain isn’t real? By the IASP’s definition, it isn’t proof. Pain without a matching image still deserves assessment.

Some signs outrank any report. Warning signs such as new leg weakness or loss of bladder or bowel control are covered in our article on acute and chronic pain, and the Centers for Disease Control and Prevention says to call 911 right away for heart attack symptoms such as chest pain or discomfort, shortness of breath, or pain in the jaw, neck, back, arms or shoulders. Losing pain sensation can be a warning too. A new patch of numbness, or an injury you did not feel happen, is worth raising with a clinician.

The Takeaway

Pain is what your nervous system concludes after combining tissue signals with everything else it knows, including what you expect and where your attention sits. That makes it adjustable, which is why expectation and distraction can change it, and fallible, which is why scans and pain so often disagree. Neither makes pain fake. In practice, neither an alarming scan nor a clean one settles what your pain means; your own description, together with a clinician’s examination, does that work.

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