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Whipple’s disease can cause a bunch of joint pain (interesting but super rare)

· fluoroquinolone toxicity

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· the acne drug Isotretinoin (Accutane) may cause joint pain and, in rare cases, symptoms that mimic rheumatoid arthritis and axial spondyloarthritis

· mycotoxin poisoning from mold

· chronic low-grade infections, probably a bigger deal than we realize (and also overlaps with some crankery)

· autonomic neuropathy

· exertional rhabdomyolysis (much more common in the era of CrossFit), and weirdly it’s  possible that “deep tissue” massage is also causing a lot of rhabdo

· poverty, the mightiest of all predictors of chronic stress in humans, is strong cause of disease and all-cause mortality — which inevitably includes chronic pain — and this relationship remains strong even in places where access to health care is more egalitarian


Pain itself often modifies the way the central nervous system processes pain, so that a patient actually becomes more sensitive and gets  more pain with  less provocation. This is called “central sensitization.” (And there’s peripheral sensitization too.) Sensitized patients are not only more sensitive to things that should hurt, but also to ordinary touch and pressure as well. Their pain also “echoes,” fading more slowly than in other people. This phenomenon is usually superimposed over other problems, but it can also occur acutely and be the primary issue, as in complex regional pain syndrome, or amplified pain syndrome, which disporportionately affects girls and young women.

Importantly, sensitization can affect our guts more than skin, muscles, and joints.  Visceral sensitization can be caused stress, which may be one reason why stress is so closely linked with abdominal pain.

For more information, see  Sensitization in Chronic Pain: Pain itself can change how pain works, resulting in more pain with less provocation .

Chronic pain does not work like acute pain

Chronic and acute pain are radically different. Chronic pain is not just acute pain that kept going. Over several weeks, the nature of pain  changes. Unfortunately, we actually still don’t have a good understanding of  how it changes. It probably involves a complex stew of the ideas in this article. For instance, sensitization (see above) is clearly a major factor. Emotional and physical stresses are strongly linked to chronic pain, but we’re not sure exactly how.

The “neuromatrix” theory of pain suggests that pain is produced by “widely distributed neural network in the brain rather than directly by sensory input evoked by injury, inflammation, or other pathology.” 2

Translation (and the important thing for desperate patients to understand):

Chronic pain rarely continues to be driven by tissue in trouble & starts to become a kind of “neurological habit” — regardless of whether any tissue is still in trouble.

chronic pain rarely continues to be driven by tissue in trouble, and starts to become a kind of “neurological habit” — regardless of whether any tissue is still in trouble. In many cases, it’s not! The pain is a kind of ghost of the original, a tormenting poltergeist. The analogy to “phantom limb pain” is strong: it’s like phantom limb pain, but without losing a body part.

Types of Pain

There are two main kinds of pain:  nociceptive and  neuropathic. Nociceptive pain is the most familiar because it arises from damaged tissue, like a cut or a burn. Neuropathic is more rare, because it is caused by damage to the damage-reporting system itself, the nervous system. Some pain, like fibromyalgia pain, doesn’t fit into either category, and was historically and poorly labelled “functional pain.” Pain is also either somatic (skin, muscle, joints) or visceral (organs).  Read more …

Psychological amplification

Not pain that’s “all in your head” pain, but pain that is seriously “ aggravated by your head.” Sometimes the brain amplifies pain substantially as a consequence of stress, anxiety, and fear. Like an ulcer, there can be a physical problem, but one that is  also sensitive to your emotional state. 3  Sometimes, the brain’s interpretation of a situation becomes a major part of the issue, or even the dominant factor — still not “all” in your head, but “a lot” in your head. Like picking at a scab, the brain can become excessively focused on a pain problem. For more information, 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 .

Amplified pain exists near one end of a spectrum: acute pain with clear cause are at one end, chronic pain driven entirely by the mind at the other. With a clear traumatic trigger, the diagnosis of “amplified” pain seems apt: there was a painful problem originally, it just got  exaggerated by the power of the mind. The more disproportionate that amplification gets, the more like pure psychosomatic pain it gets…

All in your head: pure psychosomatic pain

Pure “all in your head” chronic pain is probably quite rare. Unexplained chronic pain is routinely chalked up to psychology. “Patients often find themselves trapped in a zone between the worlds of medicine and psychiatry, with neither community taking full responsibility.” ( O’Sullivan ) But, in most cases, there’s a diagnosable cause that simply hasn’t been diagnosed yet, and that’s the main reason this article exists. Most pain patients need better diagnosis, not a psychiatrist.

But at least a few probably  do need a psychiatrist. Pure psychosomatic pain probably does exist. Tension headache is a common, minor example of how mental state can directly drive pain with no clear intermediate mechanism. Amplified pain is a much more extreme example, which makes it quite clear that psychological factors can  dominate chronic pain. The phenomenon of  conversion disorder makes it even clearer: seizures, paralysis, blindness, and other neurological symptoms in the absence of neurological disease. 4 

Strange but true! If we can paralyze ourselves with our minds, we can probably make ourselves hurt too.

Strange but true! If we can paralyze ourselves with our minds, we can probably make ourselves hurt too. In fact, pain might actually one of the members of the conversion disorder family, just undiagnosable — because pain  can have so many other causes (whereas seizures, paralysis, and blindness have relatively short lists of possible causes to eliminate, leaving only the power of mind to explain the problem). No one really knows.

Even the most psychological of all cases of chronic pain very likely still have a  seed, something that original inspired the pain, making them extreme cases of “amplified pain” (see previous section), and not technically “pure” psychosomatic pain. But if the trigger is subtle enough, relative to the psychosomatic consequences, then it’s psychosomatic for all intents and purposes, and the trigger no more defines the problem than a grain of sand defines a pearl.

Pain with literally no specific cause

Like other complicated things in life, pain may not have  any specific cause at all. Although we often speak of pain being  multifactorial, we still tend to assume that just  one of those factors is the specific cause of pain, and the others — sleep loss, stress, etc — are only  piling on, making a bad situation worse. That picture may be wrong: some chronic pain is probably an  emergent property of a big mess of synergistic stresses, with literally  no specific cause. It may crop up  only with an unholy combination of many factors. This is a  systems perspective on pain  and malaise.

How does nothing in particular actually make us hurt? There are two major key neurobiological processes:  sensitization  and  neuroinflammation  lower our thresholds for pain and malaise. They can occur independently but are usually entangled. They are set in motion by major trauma and disease, but — and this is the systems perspective — potentially also just by a variety of stresses, none of which would be enough to cause trouble on its own.

The idea of pain that truly has no specific cause is something more patients probably need to consider. Pain without no one cause is a good news scenario in the sense that it might be treated by relieving enough of the contributing factors … but bad news in the sense that it may be like fighting a hydra.

For more information, see  Vulnerability to Chronic Pain: Chronic pain often has more to do with general biological vulnerabilities than specific tissue problems .

“Spasms”: cramps, dystonia, spasticity, etc

Muscle tissue is  everywhere — our most massive biological system — and its subtler hijinks can cause a lot of discomfort without giving itself away. No one has any doubt about the cause of pain when they get a massive calf or foot cramp, but not all cramps are so obvious, and there are other types of insidious, uncomfortable muscle contractions.

This is a broad category of trouble, which contains a number of specific examples, some of which are discussed below, like “trigger points” and the “multiple sclerosis hug” (spasticity of the ribcage), and vaginismus (spasticity of the vaginal and pelevic floor muscles). Using just a wide brush for now, the types of unwanted contractions that cause the most trouble without being easy to diagnose are cramps, dystonia, and spasticity. “Spasm” — as in a “back spasm” — is an informal and non-specific term that could be used to “explain” a lot of musculoskeletal pain, and could refer to any of the more specific types of pathological contractions.

Fun fact: if your muscles are contracted for long enough, they will actually “freeze” like that: essentially scarred into place, a phenomenon called “contracture.” 5

See  Cramps, Spasms, Tremors & Twitches: The biology and treatment of unwanted muscle contractions .

Referred pain

Illustration of a dog barking up the wrong tree, representing the clinical problem with referred pain. The tree is labelled “where it hurts.” Behind the dog, pointing away, is another label: “the cause.”

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