Sensitization in Chronic Pain Pain itself can change how pain works, resulting in more pain with less provocation SHOW SUMMARY

Pain itself often modifies the way the central nervous system works, so that a patient actually becomes more sensitive and gets more pain with less provocation.12 It’s called “central sensitization” because it involves changes in the central nervous system ( CNS ) in particular — the brain and the spinal cord. Sensitized patients are not only more sensitive to things that should hurt, but sometimes to ordinary touch and pressure as well. Their pain also “echoes,” fading more slowly than in other people. This is also sometimes called “amplified pain.”

In more serious cases, the extreme over-sensitivity is obvious. But in mild cases — which are probably quite common — patients cannot really be sure that pain is actually worse than it “should” be, because there is nothing to compare it to except their own memories of pain.

Everyone needs to know about sensitization: it’s owner’s manual stuff. It is one of the major basic causes of being generally vulnerable to pain. After explaining the basic science of it, I will also offer some of my own ideas about treatment and what it all means for patients and professionals.

How sensitization works

This awful thing is actually quite easy to create in the lab, like a mad scientist’s monster. Any kind of noxious stimuli can trigger the change — anything that hurts skin, muscles or organs — and it can be reliably detected with special equipment. The role of sensitization in several common diseases34 has been well-documented, and could even be provoked by an irritant as unremarkable as muscle aches.5 It can also persist and worsen in the absence without apparent provocation. And there’s peripheral sensitization too.6

Indeed, this neurological meltdown is such a consistent complication of other painful problems that some researchers now believe central sensitization is actually a major common denominator in most stubborn pain problems. It may be what puts the “chronic” in chronic pain, giving all such problems shared characteristics regardless of how they got started — not the cause of the pain, but the cause of its chronicity.

The existence of central sensitization is not in doubt. What is still unknown is why it happens to some people and not others. Both environment and genetics are probably factors — aren’t they always? — but which genes, and what things in the environment? We just do not know yet, although we can certainly make an educated guess that it probably involves stress:

Chronic pain often outlives its original causes, worsens over time, and takes on a puzzling life of its own … there is increasing evidence that over time, untreated pain eventually rewrites the central nervous system, causing pathological changes to the brain and spinal cord, and that these in turn cause greater pain. Even more disturbingly, recent evidence suggests that prolonged pain actually damages parts of the brain, including those involved in cognition. ~ The Pain Chronicles, by Melanie Thernstrom

Diagnosing sensitization

Another unfortunate gap in our scientific knowledge is that there are no clear criteria for diagnosing central sensitization. There is no easy lab test or checklist that can confirm it.7 It could be present in nearly any difficult case of chronic pain, but it’s not a sure thing — the pain could still be coming from a continuing problem in the tissue, with or without central sensitization muddying the waters.

That all said, here are a few things that may indicate sensitization. The more of these items you check off, the more likely you are to be sensitized. (These items are taken from many sources, but particularly Smart et al.8)

Starting with the obvious: you have no obvious cause for your pain, no recent injury, no known source for the pain. You are medically unexplained.

Starting with the obvious: you have no obvious cause for your pain, no recent injury, no known source for the pain. You are medically unexplained. Your pain is chronic. Sensitization usually requires months to establish itself.

Your pain is chronic. Sensitization usually requires months to establish itself. Your pain is out of proportion to any known, recent injury.

Your pain is out of proportion to any known, recent injury. It’s hard to tell what’s going to make you feel better or worse. While some things may help or hurt consistently, others do not. You have good days and bad days and can’t figure out why.

It’s hard to tell what’s going to make you feel better or worse. While some things may help or hurt consistently, others do not. You have good days and bad days and can’t figure out why. You are seriously pessimistic, and you have a lot of worries about it being a sign of something worse (e.g. catastrophizing).

You are seriously pessimistic, and you have a lot of worries about it being a sign of something worse (e.g. catastrophizing). You have too much pain and tenderness elsewhere: sore anatomy that “shouldn’t” be sore because it’s unlikely to be related to your neck pain.

You have too much pain and tenderness elsewhere: sore anatomy that “shouldn’t” be sore because it’s unlikely to be related to your neck pain. A history of troubles in the areas that are strongly associated with sensitization: neck and shoulders, low back, abdomen, jaw.

A history of troubles in the areas that are strongly associated with sensitization: neck and shoulders, low back, abdomen, jaw. High overall stress load: exhaustion, poor sleep, chronic stress, anxiety, depression, and/or anything else that drains or menaces you (like another significant medical problem). Obviously almost any adult without a perfect life could check this one off, but it’s a matter of degree.

High overall stress load: exhaustion, poor sleep, chronic stress, anxiety, depression, and/or anything else that drains or menaces you (like another significant medical problem). Obviously almost any adult without a perfect life could check this one off, but it’s a matter of degree. You’re female. Unfortunately, this really is a risk factor!

You’re female. Unfortunately, this really is a risk factor! Overuse of stimulants like nicotine, caffeine, or more potent ones. Or withdrawal from sedatives like benzos (Valium), which can jangle your nerves for a surprisingly long time (months).

Hallucinating pain

One easy way to understand central sensitization is that it causes pain hallucinations: a bogus perception, but instead of seeing lizards on the walls, you feel pain that is out of proportion to the stimulus, because of haywire neurology (not psychology, not “all in your head,” not malingering).

There are some related conditions that are easier to understand because the stimulus is external. For instance, hyperacusis is an increased sensitivity to sounds, usually specific frequencies and volumes. Imagine a restaurant that sounds as loud as a rock concert. My father, a Vietnam veteran with PTSD, suffers from this condition. He hallucinates loudness. He spent a long time re-calibrating his sense of what “loud” is as part of therapy; a big part of that was asking my mother for opinions on the loudness of sounds, and trusting her judgement: yes, it really is loud in here or no, this really isn’t very loud. By frequently checking his perception against a healthy, objective assessment, he is partially able to adjust his subjective volume scale.

But pain hallucination is a completely personal and internal experience, and there’s no good way to check the validity of your pain. No one can tell you, no, that really isn’t very painful. They cannot know.9

Sensitization is like a "too loud" interpretation of something that would hurt even if you weren’t sensitized.

Some experts object to the term “hallucation” here, but it’s a metaphor, not a literal explanation. The problem is all-too real and physical. Although it is influenced by psychology — what isn’t? — but it’s mainly about glitchy neurology, and it’s no more “in your head” than epilepsy. The hallucation metaphor is apt in the sense that hallucinations can be caused by real neurological problems, not imagination or hypochondria. When you feel more pain than makes sense, it means that the nervous system itself is damaged, rather than the tissues it’s supposed to be reporting on. The pain system is borked. This may actually constitute an entire separate type of pain, distinct from neuropathic pain.10

Health care for pain problems remains overwhelmingly preoccupied with structural & biomechanical causes — they exist, but therapists hoping to diagnose pain that way are generally barking up the wrong tree. The last 20 years of pain science strongly suggest that neurology is by far the most important factor in most chronic pain.

Visceral sensitization

Sensitization can be selective, affecting your guts disproportionately, rather than skin, muscles, and joints: visceral sensitization instead of somatic sensitization. This may happen specifically as a consequence of stress.11 Stress biology expert Robert Sapolsky: “Stress can blunt the sort of pain you feel in your skin and skeletal muscles while increasing the sensitivity of internal organs like the intestines to pain. And that is the profile seen in irritable bowel syndrome patients.”12 This may one broad explanation for why stress is so closely linked with abdominal pain particularly (though of course there are plenty of other mechanisms for abdominal pain).

Making a bad situation worse: the trouble with not knowing the neurology

Even the clearest localization of pain in one area may, in fact, be originating from a distant area … . The reference of pain implies the existence of convergence of inputs within the spinal cord. This leads to the necessary involvement in central neural circuits in the simplest of peripheral disorders. It also leads to the possibility that the basic disorder is entirely central … ~ Professor Patrick D. Wall, FRS, DM, FRCP, in the Foreword to Muscle Pain: Understanding its nature, diagnosis and treatment

Pain is a warning system, and central sensitization is therefore a disease of over-reaction to threats to the organism — a hyperactive warning system. When physical therapists, massage therapists and chiropractors treat chronic pain patient too intensely, they may trigger that alarm system, potentially making the situation worse.

Central sensitization is bad news, but worse still is how few health care professionals are aware of the neurology and make things worse with careless or even deliberately rough, no-pain-no-gain treatment. It’s bad enough that ignorance of central sensitization leads to wild goose chases and patients riding a merry-go-round of expensive and ineffective therapies, but many kinds of therapy are also quite painful — and can make the problem worse. With tragic irony, the most likely victims are also the most vulnerable and desperate patients, patients going through the therapy grinder, their hopes leading them right into the hands of the most intense therapists.

The science of central sensitization is not all that new, but its surprising clinical implications are still emerging, and resisted by many health care professionals thinking well inside the box they were taught in. Their minds are firmly made up that pain is mainly “in” tissues, something wounded or irritated inside your meaty, gristly anatomy. Of course, trouble with tissues is important too — but the science has shown us that it is much less dominant a factor than anyone used to think. Countless studies now have shown a surprising, counter-intuitive disconnect between symptoms and problems plainly visible on scans.13 Or, in rheumatoid arthritis, patients often suffer more pain than expected from just the inflammatory erosion of their joints14 — and sensitization is probably the explanation for the “spread” of pain beyond their joints.15 Factors like poor sleep quality may drive up sensitization, and thus are more of a cause of pain than anything going on in the tissues.16

It’s actually quite astonishing how little pain is caused by some seemingly dramatic issues in your tissues! “The evidence that tissue pathology does not explain chronic pain is overwhelming (e.g., in back pain, neck pain, and knee osteoarthritis).” (Moseley)

It all starts to make a lot more sense when you understand how the your pain system works — that pain is strongly regulated by the brain.

Professionals may pay some lip service to the importance of integrating neurological considerations into treatment, but their respect is often more poetic and politically correct than practical.17 Care for chronic pain of all kinds needs to soothe and normalize the nervous system — not challenge it with vigorous manipulations.

Here’s a good description of the “therapy grinder” experience, from writer Joletta Belton. It’s not about sensitization per se — though sensitization probably is a part of her story, as it is for most people with serious chronic widespread pain — but it certainly captures the feeling of the therapeutic wild goose chase, which anyone with sensitization will recognize: I went through physical therapy, cortisone injections, surgery, more physical therapy, yoga, massages, acupuncture, chiropractors, posture-based movement therapy, changing my diet, mindfulness training … you name, I tried it. With each new therapist, each new treatment, each new attempt I was desperate for it to work, desperate for me to be fixed. And with each new therapist, each new treatment, I was devastated when I wasn’t. Oh, I would see some successes, especially when I was receiving the treatment itself. But as soon as I got home again, to life, to my worries, fears, anxieties, to my routines and habits, the pain would always come back. Sometimes in hours, sometimes days. Sometimes I even got a week or two of relief. Of hope that I was cured, that the pain was gone for good. But the pain would always come back. Often times less, but always back. And sometimes worse.

Diagnosis: how can you tell if you’re sensitized?

There is no clinical test for it. You can’t pee on a stick that changes colour. It can’t be detected in your blood, or on any scan.

So how do you know if you’re feeling pain more than makes sense? Unfortunately, a pain patient cannot compare notes with anyone: “Does that seem really painful to you? Or is that just my sensitization?”

Patients with stubborn pain problems have to try to decide if their pain is out of proportion to stimuli, if they are experiencing “too much” pain, more than seems to “make sense.” It’s not an easy question to answer! When we hurt, it always seems like a big deal!

Again, it’s just like a patient with hyperacusis trying to figure out if sounds are actually too loud, or just seem that way. But it’s easier for them because sounds are a shared experience: they can literally just ask other people, “How loud was that on a scale of 10?” Or literally measure it with a sound level meter!

For pain patients, there’s never any way to be completely sure that there isn’t an undiagnosed, ongoing cause of pain. Two examples:

A friend of mine suffered for years from relentless back pain before a little tumour was finally discovered: it was benign, but it was pressing on a nerve in his back, and had just about ruined him. After an easy surgery, he was basically completely cured, just like that. But before the diagnosis, "sensitization" was assumed! And he undoubtedly was suffering from central sensitization, but it was being constantly wound up by an unsolved problem in his back!

A very personal story: for about a year, I suffered from a terrible sensation of something stuck in my throat, a kind of pain. After many months, with no medical evidence of a specific cause, I started to gain confidence that there was nothing really going on in my throat except a sensitization problem. At least three competent professionals told me the same. We were all wrong. I simply had a rare, tricky problem to diagnosis: something was literally stuck in my throat. When it was removed, I got mostly better fast, and then took a couple years to recover from the leftover sensitization, which was severe. The experience was traumatic and complicated.

Those are great examples, but it can happen with essentially any hard-to-diagnose problem … and there are definitely a few of those. Sensitization is common, and problems that evade serious attempts at diagnosis are relatively rare … but it’s a possibility no chronic pain patient can or should ever completely eliminate.

You’ve got some nerve Pay attention to this. Not much else matters if this part of you isn’t happy.

Avoid common sources of aggravation in therapy

Be extra cautious about painfully intense therapies and skeptical of biomechanical explanations for your pain (i.e. “you hurt because you have a short leg”) — such factors are only part of the picture, and probably the least important part. Make sure any professional you see is aware of the phenomenon of central sensitization, and start using that as a criteria for judging the quality of their services — if your doctor or therapist doesn’t act like they know what central sensitization is, take your business elsewhere.

You might go through quite a few professionals before finding one who shows some “sensitivity to sensitivity.”

Medications for sensitization

Medications that work on the central nervous system18 are potentially a treatment option for serious pain system dysfunction. But here be dragons: pharmacotherapy for chronic pain has many hazards, can easily backfire, and you need the assistance of an expert with a healthy respect for the risks. The best place to look for the right kind of doctor is in a pain clinic — if you have serious chronic pain, you should start looking for one today.

When the primary complaint is pain, the treatment of pain should be primary. ~ Barrett Dorko, Physical Therapist, online discussion, 2010

Avoidance and exposure: the basics of re-calibration

No one actually knows how to treat sensitization. If they did, it would deserve a Nobel prize! But, if it’s possible at all, it must be a “re-calibration” in principle: teaching the pain system what a “normal” stimuli is. Avoidance and exposure are opposites, but they are both the main general ideas about how re-calibration might be achieved.

Avoidance means avoiding pain, minimizing aggravation, being as gentle and protective of the body part as possible, basically trying to give the nervous system a chance to slowly "calm down." A less freaked out nervous system is less likely to overreact to stimuli.

Exposure means exposing yourself to the pain, gently and cautiously challenging the body, probably mainly with activity and exercises. Other kinds of stimulation are potentially useful as well, however. The idea here is to get USED to stimulation, to repeatedly demonstrate to the nervous system that nothing terrible happens if you move a little bit like this … and then a little more the next day … and so on. Exposure can be conservative and methodical, baby-steps, or it can be an extreme “tough love” approach (as vividly detailed in a 2019 episode of the podcast Invisibilia, which attracted some intense criticism19).

A sensible approach to recalibration is to do both avoidance and exposure, probably starting with avoidance, and then shifting gradually to exposure. In other words, “calm shit down” and then “build shit up”20 — a very basic model for all rehab and recovery that happens to be especially applicable to sensitization.

But this is very broad strokes. The devil is undoubtedly in the details, and it’s all creative guess work. Re-calibration is surely an extremely personal and psychological process, with no guarantees it’s possible.

Being kind to your nervous system

Avoidance is basically all about making your life less stressful: gentler, easier, safer. Confidence and safety are critical.

Centralization of pain is the process of the central nervous system’s “opinion” of the situation becoming more important than the actual state of the tissues. This is not an “all in the head” problem, but a “strongly affected by the head” problem, like an ulcer that is caused by a very real bug but is severely aggravated by stress.

When your CNS is “freaked out” and over-interpreting every signal from the tissues as more painful than it should, therapy becomes more about soothing yourself and feeling safe than about fixing tissues. Pain is, at a very fundamental level, all about your brain’s assessment of safety: unsafe things hurt. If your brain thinks you’re safe, pain goes down.

So, for the chronic pain sufferer, cultivating “life balance” and peacefulness is a logical foundation for recovery, more important than just a pleasing philosophy — and it’s a worthwhile challenge even if it fails as therapy, of course. This is what I always meant by the idea of “healing by growing up,” long before I had even heard of central sensitization.

I have compiled a list of vulnerability reduction projects. See: Vulnerability to Chronic Pain: Chronic pain often has more to do with general biological vulnerabilities than specific tissue problems.

The best evidence for treating persistent pain points towards improving general health, as opposed to fixing specific “issues in the tissues.” ~ Playing With Movement, by Todd Hargrove, p. 217

Avoidance/exposure in hyperacusis treatment: an easier example to understand

Avoidance/exposure is basically how hyperacusis (sensitized hearing) is often treated. These patients need to avoid excessive/uncontrolled noise as much as possible … and slowly expose themselves, in an easy and controlled way, to louder and louder noises. They need to build trust that the noises they expose themselves to are not very loud. If the source of a noise is unknown, then they may experience is as being louder than it actually is, and that’s not going to re-calibrate anything. But if the noise is coming from a source the patient feels clear about — and knows it can only be so loud — that can help re-calibrate their volume sensitivity.

With pain, unfortunately it’s a lot harder to know how much a stimuli or an exercise “should” hurt. There’s no way to objectively verify that. Which is probably exactly why the pain system can get so out of whack, and the main reason sensitization is so tricky to reverse.

Some advice for professionals

At the end of this section, I provide some practical sensitization-friendly treatment principles in point form — but they follow almost automatically from education and awareness, which is the main thing. Professionals need to get their bums into gear and simply learn more about central sensitization and pain neurology generally. Once you’ve learned more about sensitization, it’s hard not to do start doing things differently.

Start deconstructing your assumptions about pain with my article on the follies and inconsistencies of structural models of pain, and also read Eyal Lederman’s more academic treatments of the same topic (on low back pain, and core strengthening). Then read Clifford Woolf’s excellent 2010 tutorial, “Central sensitization: Implications for the diagnosis and treatment of pain” — it’s heavy reading, but worth the mental exertion.

There are two websites that consistently produce good, readable, science-based information and resources about central sensitization and related topics: Body In Mind and the NOI Group. Also, physical therapist Diane Jacobs is extremely active on Facebook, constantly sharing valuable information on this theme on her page, Neuroscience and Pain Science for Manual Physical Therapists.

Above all, please start treating chronic pain patients like they might have a janky nervous system that is over-reacting to every possible perceived threat — and stop chasing the red herrings of subtle biomechanical problem of dubious clinical relevance, that are mostly nearly impossible to prove or treat anyway, and which often lead you to try to apply to much pressure to tissues. For example, a massage therapist once inflicted extreme discomfort on my armpit because she believed that there were evil “restrictions” in there and that she could rip her way to a cure of a shoulder problem I didn’t even really have. All she accomplished was to swamp my nervous system with nociception, and it could have been disastrous if I’d been a chronic pain patient.

Instead of trying to “fix” anything, seek to create (or at least contribute to) a felt experience of wellness. Make therapy pleasant, easy, and reassuring. Help the patient remember what it’s like to feel safe and good.

This transition can be immensely liberating: it can put an end to the wild goose chases for sources of pain in the tissues in many of your toughest cases.

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About Paul Ingraham I am a science writer in Vancouver, Canada. I was a Registered Massage Therapist for a decade and the assistant editor of ScienceBasedMedicine.org for several years. I’ve had many injuries as a runner and ultimate player, and I’ve been a chronic pain patient myself since 2015. Full bio. See you on Facebook or Twitter.

Appendix: The actual Woolf abstract

You can see why I thought it needed translation. 😜 I've added a few annotations in square brackets and footnotes.

“Central sensitization: Implications for the diagnosis and treatment of pain”

Woolf. Pain. Volume 152, Number 2 Suppl, S2–15. Oct 2010.

Nociceptor inputs [noxious stimuli] can trigger a prolonged but reversible increase in the excitability and synaptic efficacy of neurons in central nociceptive pathways, the phenomenon of central sensitization. Central sensitization manifests as pain hypersensitivity, particularly dynamic tactile allodynia,21 secondary punctate or pressure hyperalgesia,22 aftersensations,23 and enhanced temporal summation.24 It can be readily and rapidly elicited in human volunteers by diverse experimental noxious conditioning stimuli to skin, muscles or viscera, and in addition to producing pain hypersensitivity, results in secondary changes in brain activity that can be detected by electrophysiological or imaging techniques. Studies in clinical cohorts [groups of people with a shared characteristic studied over time] reveal changes in pain sensitivity that have been interpreted as revealing an important contribution of central sensitization to the pain phenotype in patients with fibromyalgia, osteoarthritis, musculoskeletal disorders with generalized pain hypersensitivity, headache, temporomandibular [jaw] joint disorders, dental pain, neuropathic pain, visceral pain hypersensitivity disorders and post-surgical pain. The comorbidity [tendency to occur together] of those pain hypersensitivity syndromes that present in the absence of inflammation or a neural lesion, their similar pattern of clinical presentation and response to centrally acting analgesics, may reflect a commonality of central sensitization to their pathophysiology. An important question that still needs to be determined is whether there are individuals with a higher inherited propensity for developing central sensitization than others, and if so, whether this conveys an increased risk in both developing conditions with pain hypersensitivity, and their chronification. Diagnostic criteria to establish the presence of central sensitization in patients will greatly assist the phenotyping [description] of patients for choosing treatments that produce analgesia by normalizing hyperexcitable central neural activity. We have certainly come a long way since the first discovery of activity-dependent synaptic plasticity in the spinal cord and the revelation that it occurs and produces pain hypersensitivity in patients. Nevertheless, discovering the genetic and environmental contributors to and objective biomarkers of central sensitization will be highly beneficial, as will additional treatment options to prevent or reduce this prevalent and promiscuous form of pain plasticity.

That may be the oddest use of “promiscuous” I have ever seen. Correct, but odd.

Related Reading

This article is tightly focused on the topic of central sensitization. For a much more general article about how pain works, see:

Pain is Weird Pain science reveals a volatile, misleading sensation that is often more than just a symptom, and sometimes worse than whatever started it ~ 11,000 words

Some other relevant articles:

See also:

Notes