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12 Surprising Causes of Pain

Trying to understand pain when there is no obvious explanation

updated (first published 2007)
by Paul Ingraham, Vancouver, Canadabio
I am a science writer and a former Registered Massage Therapist with a decade of experience treating tough pain cases. I was the Assistant Editor of ScienceBasedMedicine.org for several years. I’ve written hundreds of articles and several books, and I’m known for readable but heavily referenced analysis, with a touch of sass. I am a runner and ultimate player. • more about memore about PainScience.com

The world is full of unexplained pain. When I worked as a massage therapist, the most extraordinarily desperate people came to see me. Two memorable examples:

  1. A woman spends three days in the hospital with severe abdominal pain, but is cleared of every possible ominous medical cause … and then comes to see me?! A massage therapist!
  2. A man gets a ride in an ambulance with severe chest and left shoulder and arm pain, but doctors cannot find anything wrong with him … and then he comes to see me.

No pressure! And now I publish a busy website, and I get an email like this more often than I change my socks:

I’ve been to every medical specialist you can imagine. They can’t find anything wrong with me. The psychiatrist says it’s not in my head, and the rheumatologist says it’s not in my body. But something is causing my pain. It’s not an infection or a fracture or a cancer. It’s not a sprain or a pinched nerve or a little man with a knife. What else is there? What else is left?

What else indeed! When “obvious” and known causes of pain have been eliminated, what next? What else causes pain? How else can pain start, change, worsen? This article summarizes ten not-so-obvious ways to hurt: twelve pain phenomena that might help you to understand pain that has defied diagnosis or explanation so far.

One of the principle qualities of pain is that it demands an explanation.

Plainwater, by Anne Carson

  1. Muscle Knots
  2. Sensitization
  3. Brain pain
  4. Pathological sensitization
  5. Vitamin D deficiency
  6. Muscle tension and contracture
  7. Referred pain
  8. The pain of stuckness
  9. Drug side effects, especially bisphosphonates and statins
  10. Analgesic rebound
  11. Stupid, stupid neutrophils
  12. Chronic low-grade inflammation and “inflammaging”

1. Muscle Knots

Muscle knots — myofascial “trigger points” — are a factor in most of the world’s aches and pains. Their biology is still mostly mysterious: conventional wisdom says they are tiny spasms, but they might also be a more pure neurological problem. Regardless, they can cause strong pain that often spreads in confusing patterns, and they grow like weeds around other painful problems and injuries, making them quite interesting and tricky. Although they are well known to many specialists and researchers, most doctors and therapists know little about them, so misdiagnosis is epidemic. See Trigger Points & Myofascial Pain Syndrome.

2. Sensitization

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. 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. See Central Sensitization in Chronic Pain: Pain itself can change how pain works, resulting in more pain with less provocation.

3. Brain pain

This is an important subcategory of sensitization: sometimes, the brain amplifies pain as a consequence of stress, anxiety, and fear. This is not “all in your head” pain, but “aggravated by your head” pain. Like an ulcer, there is a real physical problem — but it just happens to be unusually sensitive to your emotional state.1 Sometimes, the brain’s interpretation of a situation becomes a major part of the issue. 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.

4. Pathological sensitization

Yet another kind of sensitization: sensitization can also be caused by disease processes we do not yet understand. The first kind of sensitization is a more-or-less normal and common reaction to chronic pain. The second kind (“brain pain”) is powered by the worries of a frazzled brain. But there are also diseases that sensitize the nervous system: not a nerve pinch or lesion, but nerve failure. For instance, complex regional pain syndrome causes extreme pain, usually in a limb, and usually following some trivial tissue insult like an insect bite or minor cut. When it’s full-blown, the nastiness of this problem is impossible to understate — suicide is common — and yet there probably are milder variations of it. Many times in my career I have become quite convinced that a patient had to be suffering from some lesser form of CRPS, awful but not enough to clinch a CRPS diagnosis.

5. Vitamin D deficiency

Vitamin D deficiency is probably more common than once suspected — at least 1 in 20 people in the lowest estimates,2 and possibly many more.3 It can cause subtle widespread pain that may be misdiagnosed as fibromyalgia and/or chronic fatigue syndrome, including symptoms like muscle and bone aching,4 fatigue and weakness, lower pain threshold, and more acute soreness after exercise that is slower to resolve. For more information, see Vitamin D for Pain.

Reserve a few minutes to read this: “The wilderness of the medically unexplained.” There’s not much in the way of a take-home message here: it’s mostly just a really well-written and heart-wrenching tale of a cancer that flew under the diagnostic radar for quite a while. It’s going to be poignant for anyone who has felt like a medical mystery … so, you know, just about everyone with chronic pain. I’m not sure that anyone involved could have done much better. Things that are tough to diagnose are tough to diagnose, and that’s just life. And death.

But please, doctors (and anyone responsible for diagnosing): try to remember that when you hear hoofbeats in Texas, sometimes it really is bloody zebras, not horses.

6. Muscle tension and contracture

Ordinary muscle tension itself can cause a surprising amount of pain. A leg or foot cramp is a common and extreme example, where no one has any doubt of the cause of pain. But imagine a muscle spasm much less strong, but lasting for days and days — or years! Although superficially a simple concept, there are actually several physiological mechanisms by which muscle can become shortened and painful for a long time, some well understood and straightforward (spasticity from neurological diseases), while others are quite mysterious (like spasms people are born with, as in torticollis or wry neck).

One particularly good and sinister example of muscle tension pain is the “MS hug”: a symptom of multiple sclerosis that feels like a painfully tight band around the chest, often experienced long before diagnosis. Although the feeling of constriction is the classic symptom, many patients also just experience widespread and erratic pain in the chest wall.

If your muscles are spasmed for long enough, they will actually “freeze” like that: essentially scarred into place, a phenomenon called “contracture.”56

7. 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.”

Referred pain results in an amazing amount of medical barking up the wrong tree.

Anything that hurts inside the body — anything under the skin — is difficult for the brain to locate. This is partly because we literally just don’t have enough nerve endings for it, and partly because the nervous system isn’t perfect and signals literally get “crossed.” The practical result of this is that internal pain with any cause may be felt somewhere completely different. Despite the fact that this phenomenon is well known, it still results in an amazing amount of medical barking up the wrong tree. Referred pain isn’t exactly a “cause” of pain, but it belongs in this list because it’s an important concept that can help to explain many pain problems that otherwise don’t make sense. For instance, both of the examples at the beginning of this article were cases where referred pain fooled doctors — in both cases, the pain was caused by a trigger point in a nearby muscle, not by vital organs. The doctors simply looked in the wrong place!

8. The pain of stuckness

Here’s a simple experiment: assume an distinctly awkward posture, and within minutes you will probably experience severe pain. Why? You haven’t ripped or torn anything. But we are wired to avoid this situation, because every cell in our body depends on nearly constant movement to survive. And so the nervous system takes it very seriously whenever tissues feels “stuck.” The exact mechanism of pain is probably nerve endings that detect tension on cartilage, ligaments and tendons. Continuous tension on these structures may be interpreted by the nervous system as a serious threat. But here’s the kicker: you can induce this reaction quickly with an obviously awkward posture … or you could do it slowly and insidiously with surprisingly subtle poor posture, muscle imbalances, joint dysfunctions, or anything that deprives tissue of full movement. When a joint feels “stuck,” for instance, and there is no obvious way (and sometimes no anatomical way) of moving to get “unstuck,” the sensation can escalate to a screaming itch-you-can’t-scratch. This is may be the main causes of neck cricks, for instance, and scads of other miscellaneous aches and pains. Unfortunately, postural correction is a challenging and sketchy business.

Actonel (risedronate) is one of the more popular bisphosphonate drugs, any of which may cause severe musculoskeletal pain years after first exposure.

Actonel (risedronate) is one of the more popular bisphosphonate drugs, any of which may cause severe musculoskeletal pain years after first exposure.

9. Drug side effects, especially bisphosphonates and statins

On January 7, 2008, the U.S. Food and Drug Administration alerted health care professionals and consumers to the unusual severe side effects of a popular class of drugs for osteoporosis and Paget’s disease, the bisphosphonate (Wikipedia). They can cause “severe and sometimes incapacitating bone, joint, and/or muscle pain” which “may occur within days, months, or years” after first taking the medication. This medication has almost certainly explained some otherwise inexplicable pain in some of my patients over the years! Alendronate and risedronate are the two most popular bisphosphonates, and they are usually prescribed for osteoporosis or for a bone-deforming condition called Paget’s disease. If you are 40+ and grappling with a mysterious pain problem, check your medicine cabinet for bisphosphonates in particular, but of course any other medication that could cause pain as a side effect.

And then there’s the statins, like Lipitor and Crestor: the drugs that lower our blood cholesterol may also cause pain. Statins are important and widely used drugs, and their deleterious effect on muscle is widely considered a diagnosable condition: statin myalgia, or statin-associated muscle symptoms (SAMS).7 A few patients, about 1 in 10,000, get a more obvious, serious case of muscle poisoning, rhabdomyolysis,8 and an even rarer and more serious condition afflicts 1 in 100,000: statin-associated autoimmune myopathy.910

And yet there is also confusion and controversy about the prevalence of statin myalgia.11 There’s even clear evidence that it could be some kind of illusion or misunderstanding: in one head-scratcher of a study, taking statins only increased pain when patients knew they were taking statins.12 So that’s weird! The truth is probably “all of the above” and “it’s complicated” — it seems likely that some patients are genuinely intolerant of statins, while others are suffering from fear of statins and/or some other cause of musculoskeletal pain (of which there many). There might also be some tricky X-factors, like vitamin D deficiency, which seems to be linked to statin myalgia.13

Fortunately, for the genuinely statin intolerant — and you probably do exist! — it’s easy to solve by lowering the dose or switching to another statin.

10. Analgesic rebound

This almost counts as a drug side-effect, but it’s an important enough phenomenon in its own right that it deserves separate description. When you take a lot of analgesics — pain-killers — it’s possible to pre-empt the production of your body’s own pain-fighting molecules. Endorphin production, for instance, will drop. This can have disastrous consequences when you stop taking the drugs, resulting in worse pain than ever. This is part of the phenomenon of the well-known serious withdrawal symptoms from some drugs; it is a less well-known problem with over-the-counter pain-killers. Although this phenomenon isn’t particularly mysterious or difficult to identify, it does show us something important about how pain works: we aren’t entirely without our own defenses, and those defenses can actually be undermined by artificial help. And there are scenarios where analgesic rebound may be difficult to detect. Given how extremely common analgesic usage is, it’s likely that people with recurrent headaches may be suffering primarily from bouts of rebound pain, occurring in the occasional gaps between erratic but generally intensive self-prescribing of pain killers.

I have a good story about a terrible withdrawal-induced headache: see my headache tutorial.

11. Stupid, stupid neutrophils

Neutrophils are defender cells that are supposed to destroy bacteria that invade wounds, a normal part of the inflammatory response to injury. Bizarrely, neutrophils go to work even when the wound is sterile, not open to the outside world. Like an overzealous police force with nothing better to do, they also attack a common cellular organ, mitochondria, whenever it is spilled from cells by injury. Mitochondria are actually honoured symbiotic guests that convert our food to energy for us. Normally we live out our lives in perfect harmony with mitochondria, biological BFFs. But when they get the chance, neutrophils target and hunt them like they are invaders14 because for millions of years they haven’t gotten the evolutionary memo that mitochondria should be left in peace.

Inflammation is excessive for this reason: every trauma causes pain that is too loud for too long, because a significant portion of the inflammation is due to this SNAFU immune system policy of attacking mitochondria. There are many perverse sources of pain in pathology, but this one really stands out as being particularly ridiculous and unfair. It does have one practical implication: it directly suggests that it’s quite reasonable to try to control and limit inflammation with things like Voltaren® and icing. Contrary to the popular notion that inflammation is “natural” and therefore good, inflammation is definitely exaggerated, and could do with some controlling!

For more information, see Why Does Pain Hurt? How an evolutionary wrong turn led to a biological glitch that condemned the animal kingdom — you included — to much louder, longer pain.

12. Chronic low-grade inflammation and “inflammaging”

Chronic, subtle, systemic inflammation is a possible factor in stubborn musculoskeletal pain. It can have many underlying causes, from bad genes to mild autoimmune disease (including allergies), smoking or other severe biological stresses, chronic infections, and even just getting old (known as “inflammaging”). The greatest culprit is metabolic syndrome: a set of biological dysfunctions strongly linked to poor fitness, obesity, aging, and likely emotional stress and sleep disturbance as well. See Chronic, Subtle, Systemic Inflammation: A possible insidious cause of mysterious chronic pain.

Chronic pain as a destiny: many causes for many years

Nothing’s ever simple and chronic pain least of all: it’s usually caused by a sinister stew of factors that eat away at people for a long time. Chronic pain may be “destiny” with roots going back many years, even decades.15 Trying to solve it by fixing one thing — like vitamin D, say — may be about as feasible as trying to fix a broken engine with just one tool. It can be an impossible puzzle to even understand, let alone treat. Elisa Arnaudo:

Medically unexplained symptoms (MUS) represent a major challenge for healthcare systems in industrialised countries. These symptoms are so prevalent that they are assessed in up to 50% of consultations in primary care.

Probably almost all MUS involve chronic pain, and Arnaudo’s post seems to be mostly about fibromyalgia. She proposes MUS patients are a stumper because of “an inadequate explanatory framework of disease.” In other words, we’re not just missing some pieces from a puzzle; it’s that we probably don’t even know what kind of puzzle we’re looking at.

And… not necessarily such a puzzle.

Ending with a ray of hope

It’s also possible that many of the explanations we need are really hovering just out of our current reach, and really not so tricky after all — just too subtle to be easy. They get missed not because the problem requires godlike medical insight, but because most doctors just don’t know that much about chronic pain and economics keeps appointments relatively short and so even some pretty straightforward things just get missed.

That possibility is the inspiration for this article. Some of the ways to hurt described above may be the main factors, or even the only factors, for some people.


About Paul Ingraham

Headshot of Paul Ingraham, short hair, neat beard, suit jacket.

I am a science writer, former massage therapist, and I was the assistant editor at ScienceBasedMedicine.org for several years. I have had my share of injuries and pain challenges as a runner and ultimate player. My wife and I live in downtown Vancouver, Canada. See my full bio and qualifications, or my blog, Writerly. You might run into me on Facebook or Twitter.

Appendix: So what happened with those two pain cases?

At the beginning of the article, I described two cases of severe undiagnosed pain:

A woman spends three days in the hospital with severe abdominal pain, but is cleared of every possible ominous medical cause … and then comes to see me?! A massage therapist!

A man gets a ride in an ambulance with severe chest and left shoulder and arm pain, but doctors cannot find anything wrong with him … and then he comes to see me.

I got lucky with both of these cases, and I was able to treat both of them quickly and easily. There are many ways to hurt, and success was hardly guaranteed. I saw many patients with strange pains I was never able to diagnose. But both of these cases involved surprisingly clear and and treatable trigger points: hypersensitive spots in muscle tissue, causing more pain than anyone thought possible.

In the woman’s case, the trigger point was in her iliopsoas muscle, a muscle deep in the abdomen and extending downward through the pelvic that is the subject of much hype and legitimate skepticism. However, it is possible to massage it in some patients. There’s very little to tell: I guessed that it might be the problem, found the trigger point, gently massaged it for a few minutes… and that was the end of her misery. Just like that!

The man’s case was even more straightforward: he had a trigger point in his pectoralis major muscle. It was easy to find, as the muscle twitched violently when I palpated it, the most robust example of a “jump sign” I ever saw. It was nasty, but in twenty minutes of massage we reduced the “heart attack” pain by 80%. The next day it was gone, and it stayed gone for as long as I knew him — years after that. I tell his story in more detail in my trigger points book.

Related Reading

What’s new in this article?

Six updates have been logged for this article since publication (2007). All PainScience.com updates are logged to show a long term commitment to quality, accuracy, and currency. more Like good footnotes, update logging sets PainScience.com apart from most other health websites and blogs. It’s fine print, but important fine print, in the same spirit of transparency as the editing history available for Wikipedia pages.

I log any change to articles that might be of interest to a keen reader. Complete update logging started in 2016. Prior to that, I only logged major updates for the most popular and controversial articles.

See the What’s New? page for updates to all recent site updates.

SeptemberScience udpate — Cited evidence that statin myalgia could be bogus, not actually a real problem.

JanuaryAdded a table of contents. A few minor edits.

2016New conclusion, with both discouraging and encouraging perspectives, taken from a recent blog post about the challenge of medically unexplained symptoms.

2016Added Vitamin D deficiency and chronic low-grade inflammation.

2016Minor addition: a sidebar about “the wilderness of the medically unexplained.”

2016Added sidebar about the basic types of pain, nociceptive and neurpathic. Added #10, about exaggerated inflammation.

2007Publication.

Notes

  1. Weren’t ulcers proved to be caused by a bacteria? That they were. Helicobacter pylori was famously hunted down in 1983 by Australian scientists Barry Marshall and Robin Warren. Although its link with ulceration was initially met with much skepticism, science came around relatively quickly — convinced by evidence, just like it’s supposed to work. By the mid-90s it was widely accepted that H. pylori infection causes ulcers, and Marshall and Warren got a Nobel prize in 2005 (acceptance speech).

    But! Most people infected with the bacterium have no symptoms, and there are many variables that determine the severity of the infection and whether or not it leads to ulcer. Stress is one of those factors (see Guo et al. and Jia et al.). Thus ulcer is very likely both an H. pylori infection and a “stress-sensitive” condition.

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  2. Manson JE, Patsy M B, Rosen CJ, Taylor CL. Vitamin D Deficiency — Is There Really a Pandemic? N Engl J Med. 2016 Nov 10;375(19):1817–1820. PubMed #27959647.

    ABSTRACT


    The claim that large proportions of North American and other populations are deficient in vitamin D is based on misinterpretation and misapplication of the Institute of Medicine reference values for nutrients — misunderstandings that can adversely affect patient care.

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  3. Holick MF, Chen TC. Vitamin D deficiency: a worldwide problem with health consequences. Am J Clin Nutr. 2008 Apr;87(4):1080S–6S. PubMed #18400738. PainSci #55028. BACK TO TEXT
  4. Bone aching is caused by osteomalacia, which is bone weakening specifically caused by malfunctioning bone building biology. The Mayo Clinic describes osteomalacia symptoms like so: “The dull, aching pain associated with osteomalacia most commonly affects the lower back, pelvis, hips, legs and ribs. The pain may be worse at night, or when you’re putting weight on affected bones.” BACK TO TEXT
  5. Csapo R, Maganaris CN, Seynnes OR, Narici MV. On muscle, tendon and high heels. J Exp Biol. 2010 Aug;213(Pt 15):2582–8. PubMed #20639419. PainSci #55265. Chronic heel wearers do have shortened calf muscles, stiffer Achilles tendons, and a smaller ankle range of motion. BACK TO TEXT
  6. Chen CK, Yeh L, Chang WN, Pan HB, Yang CF. MRI diagnosis of contracture of the gluteus maximus muscle. American Journal of Roentgenology. 2006;187(2):W169–74. PubMed #16861506. PainSci #55849.

    From the abstract: “Gluteal contracture manifests characteristic features on MRI, including an intramuscular fibrotic cord extending to the thickened distal tendon with atrophy of the gluteus maximus muscle and posteromedial displacement of the iliotibial tract.”

    BACK TO TEXT
  7. Di Stasi SL, Macleod TD, Winters JD, Binder-Macleod SA. Effects of Statins on Skeletal Muscle: A Perspective for Physical Therapists. Phys Ther. 2010 Aug. PubMed #20688875. BACK TO TEXT
  8. “Rhabdo” is a nasty but also very interesting condition. I discuss it in detail in Poisoned by Massage. BACK TO TEXT
  9. Mammen AL. Statin-Associated Autoimmune Myopathy. N Engl J Med. 2016 Feb;374(7):664–9. PubMed #26886523. BACK TO TEXT
  10. Regarding classification, professionals should take a look at a great 2004 interview with Eliot A. Brinton, MD: “There are 4 interrelated terms for muscle problems that can occur with statins. Unfortunately, they are often confused even by healthcare professionals ….” (Technical note: this document is freely available, but direct linking will hit a paywall. Medscape only reveals the whole thing to people arriving from a Google search. Simply search for do a Google search for it to get around the paywall.) BACK TO TEXT
  11. Ganga HV, Slim HB, Thompson PD. A systematic review of statin-induced muscle problems in clinical trials. Am Heart J. 2014 Jul;168(1):6–15. PubMed #24952854.

    In this review of several statin trials, only slightly more patients had pain on statins than without (placebo): just 12.7%, compared to 12.4%. You could conclude from this data that there actually is no such thing as statin mylagia! But it probably probably is a real phenomenon, which is highly plausible based on the existence of rarer but very severe side effects on muscle (see Mammen or Statin Therapy). We don’t have very good data about it, it’s mostly not severe, and it’s hard to distinguish from the “background noise” of many other common causes of musculoskeletal pain.

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  12. Gupta A, Thompson D, Whitehouse A, et al. Adverse events associated with unblinded, but not with blinded, statin therapy in the Anglo-Scandinavian Cardiac Outcomes Trial-Lipid-Lowering Arm (ASCOT-LLA): a randomised double-blind placebo-controlled trial and its non-randomised non-blind extension phase. Lancet. 2017 Jun;389(10088):2473–2481. PubMed #28476288.

    This study was designed to test the existence of the phenomenon of statin myalgia. Taking statins did not increase pain in patients when they were unaware that they were taking them. This suggests that statin myalgia is something people get because they are afraid of it, not because it’s a real side effect. As the authors concluded:

    These analyses illustrate the so-called nocebo effect, with an excess rate of muscle-related AE reports only when patients and their doctors were aware that statin therapy was being used and not when its use was blinded. These results will help assure both physicians and patients that most AEs associated with statins arenot causally related to use of the drug and should help counter the adverse effect on public health of exaggerated claims about statin-related side-effects.

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  13. Michalska-Kasiczak M, Sahebkar A, Mikhailidis DP, et al. Analysis of vitamin D levels in patients with and without statin-associated myalgia - a systematic review and meta-analysis of 7 studies with 2420 patients. Int J Cardiol. 2015 Jan;178:111–6. PubMed #25464233. BACK TO TEXT
  14. McDonald B, Pittman K, Menezes GB, et al. Intravascular danger signals guide neutrophils to sites of sterile inflammation. Science. 2010 Oct;330mcd(6002):362–6. PubMed #20947763. BACK TO TEXT
  15. Burke NN, Finn DP, McGuire BE, Roche M. Psychological stress in early life as a predisposing factor for the development of chronic pain: Clinical and preclinical evidence and neurobiological mechanisms. J Neurosci Res. 2016 Jul. PubMed #27402412. “Early-life adversity increases the risk of developing a number of disorders, such as chronic pain, fibromyalgia, and irritable bowel syndrome.” BACK TO TEXT