“I, too, have been assigned months of futility, long and weary nights of misery. When I go to bed, I think,`When will it be morning?' But the night drags on, and I toss till dawn...Depression haunts my days. My weary nights are filled with pain as though something were relentlessly gnawing at my bones.”

Job suffered badly. And his Old Testament woes are considered by many to be one of the earliest descriptions of fibromyalgia, a painful, puzzling disorder that still has experts bickering and patients frustrated, bereft of relief. The Bible isn't exactly a paragon of medical accuracy, but Job’s ailment does sound an awful lot like the modern interpretation of fibromyalgia. The classic diffuse pain, aches and discomfort aren’t the half of it; depression, fatigue, stiffness, sleep loss and generally just feeling really bad are common too. Fibromyalgia patients — 2 percent to 8 percent of the population — have also endured decades of dismissals that it's all in their head — a psychosomatic conjuring, a failure of constitution.

Skepticism around fibromyalgia stemmed in part from an elusive organic explanation. Symptoms appeared to arise out of nowhere, which didn't make any sense to empirically minded physicians. But over the past two decades, research has brought clinicians closer to deciphering this mysterious pain state, once thought muscular in nature, now known to be neurologic. Based on this recent work a new article in the Journal of the American Medical Association by chronic pain expert Dr. Daniel Clauw brings us up to speed on the understanding, diagnosis and management of fibromyalgia circa 2014. And the outlook for patients is rosier than you might expect given the condition’s perplexing reputation.

Accounts of chronic pain states and rheumatologic conditions — those affecting the joints or connective tissues — go way back. Hippocrates described gout, 2nd century Ayurvedic practitioners diagnosed what sounds like rheumatoid arthritis, and medieval European clinicians — and later French physician Guillaume de Baillou — ascribed joint and muscular maladies to “rheumatism” — the “rheum,” Greek for “river” or “flow” — of bad humors into affected areas. Eventually healers began distinguishing between articular rheumatism, that affecting the joints, and muscular rheumatism. Out of this idea of a generalized muscular pathology arose descriptions close to the modern view of fibromyalgia. But not that close.

Theories on what caused muscular rheumatism echoed through lecture halls for nearly a century — muscle spasms were the cause, or nerve dysfunction, possibly muscular calluses — until one took hold, that the condition was due to inflammation of fibrous or connective tissue in the muscles. As a result, muscular rheumatism came to be called “fibrositis” for the better part of the twentieth century. Despite the widely accepted description, the diagnosis remained vague; the pathological findings inconsistent or non-existent. And soon another theory added to the confusion: that fibrositis was rooted in the psyche. In 1880 an American neurologist had attributed what would come to be called fibrositis to the stress and anxiety of modern life. But it wasn't until World War II, when the diagnosis was common among hospitalized soldiers, often in association with depression and the stress of war, that psychological theories found traction. One group suggested fibrositis be called “psychogenic rheumatism”; another claimed it arose “independently of gross anatomical disease…”

By the second half of the 20th Century descriptions of fibrositis better integrated physical and psychological symptoms. In 1968 an Illinois physician branded the disorder a constellation of generalized stiffness, headaches, malaise, and tender points occurring almost exclusively in women who tended to be “worry worts.” His symptom description holds up relatively well; the girls-only idea, as we’ll see and as suggested by the afflicted WWII soldiers, not so much. Unfortunately it was definitions like this that may have contributed to subsequent, often sexist interpretations of fibrositis — that it was a byproduct of reckless emotion in the, almost always, female brain.

In the late 1970s, the term fibromyalgia replaced fibrositis, as inflammation had taken an etiologic back seat, while work by Dr. Hugh Smythe honed diagnosis. Smythe, considered a fibromyalgia pioneer, better identified common tender points. Along with colleague Harvey Moldofsky he confirmed the condition’s associated sleep disturbances using EEG. He also posited theories on how the pain patients experience might be referred, or perceived in an area other than where it's generated. 1981 saw the first study confirming the reliability of the diagnosis against controls. And finally in 1990 the American College of Rheumatology released the first official fibromyalgia diagnostic criteria; a history of widespread pain and pain in at least 11 of 18 specified tender points were necessary for a diagnosis.  

Despite the clinical clarity, medicine still lacked a physical explanation for fibromyalgia, leading many experts to implicate the brain. The next 20 years of research confirmed their suspicion, culminating in today’s understanding of the disorder as a “centralized pain” state, as Dr. Clauw’s review discusses. “Centralized” refers to the central nervous system — the brain and spinal cord — either originating or amplifying pain. As Clauw points out, the CNS of patients with fibromyalgia appears to both heighten the response to painful stimuli and perceive normally non-painful stimuli as painful. A major implication here is that fibromyalgia and possibly related states like chronic fatigue syndrome are drastically different in origin than other conditions common to rheumatology clinics like osteo- and rheumatoid arthritis, both of which result in discernible tissue damage.

Neuroimaging studies support the theory that fibromyalgia-afflicted brains exhibit enhanced sensory response to benign stimuli. But what leads to this centralized pain state? Fibromyalgia’s strong familial association suggests that genetics plays a major role. Also any number of environmental influences can trigger fibromyalgia including infection, physical pain and psychological trauma. Deployment to war is still considered a major risk factor. And it seems there can be a significant psychological or behavioral component to the condition. Fibromyalgia patients are more likely to suffer from depression, anxiety and post-traumatic stress disorder that in many cases, Clauw speculates, might result from common triggers. Regardless of the inciting factor, altered levels and activity of neurotransmitters that facilitate pain transmission may ultimately lead to the symptoms of fibromyalgia. These central disturbances are also likely at the root of the non-pain symptoms of fibromyalgia, as the same neurotransmitters are involved in sleep, memory and mood.

The science of fibromyalgia has clearly progressed. But perhaps most encouraging for patients are advances in the clinic, not the lab. Using the 1990 ACR diagnostic criteria, nearly all qualifying patients are women, harkening back to an earlier era of misunderstanding. However per newer, seemingly more accurate guidelines — which consider a wide range of symptoms and do away with tender point counts — the female to male ratio is 2:1, similar to that of other chronic pain conditions. Despite lingering stigma, Clauw reassures that receiving a correct fibromyalgia diagnosis is usually a major relief for patients: fewer doctor visits, fewer tests, fewer bills.

Better still for fibromyalgia sufferers is that it’s now relatively treatable. Several neurotransmitter-modulating drugs and drug classes appear to be effective, including some pain medications and antidepressants. Among these, three treatments are now FDA-approved. Possibly more effective, according to the current evidence, are exercise, cognitive-behavioral therapy — a form of psychotherapy based in altering negative thoughts and behaviors — and simply patient education. Clauw stresses that while medications can help alleviate symptoms, patients rarely see significant symptom improvement without also adopting self-management approaches like stress reduction, quality sleep and exercise.

As in many conditions, there are countless alternative fibromyalgia therapies out there too, from yoga to licorice to acupuncture. Despite minimal supporting evidence Clauw says try away, so long as they don't cause any harm. “…evidence suggests that these therapies give patients a greater sense of control over their illness…Giving patients a choice of therapies may improve the likelihood for a placebo response by activating the body’s internal analgesic mechanisms,” he writes. And for the herbal enthusiasts, a recent National Pain Foundation report suggests that marijuana might be more effective in fibromyalgia than most available drug therapies.

Exactly what fibromyalgia is, and what causes it, might be argued for some time — there are still plenty of online skeptics, including clinicians, writing it off as a fabrication of the malingering or “hysterical” patient. But Clauw and colleagues have advanced medicine’s grasp on the condition, culminating in a relatively unified, more accurate definition. The idea of centrally derived or enhanced pain reflects just how much influence the brain’s tangle of some 85 billion neurons has over the body — that corporeal perception can be strongly colored by central nervous system interpretation. It also suggests that fibromyalgia treatment should likely target neural networks and neurotransmitters, not joints, muscles or misguided humors. With this in mind, in 2014, it’s clear that fibromyalgia is real, for many it’s treatable and hopefully more effective treatments are around the corner — medical breakthroughs come a whole lot easier when you know where to look.

Are you a scientist who specializes in neuroscience, cognitive science, or psychology? And have you read a recent peer-reviewed paper that you would like to write about? Please send suggestions to Mind Matters editor Gareth Cook, a Pulitzer prize-winning journalist and regular contributor to NewYorker.com. Gareth is also the series editor of Best American Infographics, and can be reached at garethideas AT gmail dot com or Twitter @garethideas.