While there is a lot of ongoing speculation about what triggers fibromyalgia, its causes have yet to be definitively identified and confirmed. Recent research has generally found that fibromyalgia is most likely a result of what scientists call central sensitization, or unusual responses in the nervous system with regard to pain perception.
Fibromyalgia’s Biochemical Triggers
“The [current] consensus is that fibromyalgia is not a problem with the muscles, joints, or tendons, but rather a problem with the central nervous system,” says Dr. Bruce Solitar, clinical associate professor of medicine in the division of rheumatology at NYU Medical Center/Hospital for Joint Diseases in New York. While it’s easy to think that pain felt by someone who has experienced no physical damage to the body might be categorized as purely psychosomatic, the sensations that a fibromyalgia patient experiences are as real as any other pain.
This was clearly demonstrated when researchers did MRI imaging of patients with fibromyalgia. When they pressed on certain areas of the participants’ bodies, they found dramatically increased activity in the pain center of the brain. One theory attributes this phenomenon to an increased release of substance P, the chemical that activates nerves when there is a painful stimulus. “In fibromyalgia patients, substance P is being released even in the absence of a painful stimulus. And there seems to be an amplified release when there is a painful stimulus,” explains Dr. Solitar. In addition, the brain’s regulatory effect, which sends “down signals” to turn off pain, also appears to be abnormal in people with fibromyalgia — so when a painful stimulus does occur, it gets amplified rather than dampened.
Fibromyalgia’s Physical and Emotional Triggers
So what causes the nervous system to malfunction in such a way? Scientists aren’t sure, but a number of conditions have been linked to the development of fibromyalgia. These include:
Infection. The Epstein-Barr virus, and the viruses that cause influenza, and hepatitis B and C have all been implicated in the development of fibromyalgia. “These viruses may have [long-term] effects on the immune system. It’s also possible that viral particles attach to glial cells, which are cells within the brain that affect neurotransmission [and influence the pain response],” says Dr. Solitar. Additionally, there is a well-established connection between Lyme disease (caused by a bacteria called Borrelia burgdorferi) and fibromyalgia: Some patients who have been treated for Lyme — and ostensibly recover from it — continue to experience the unusually high frequency of unprovoked pain that characterizes fibromyalgia.
Trauma. Sometimes the development of fibromyalgia is linked to physical injury, especially in the upper (cervical) spine. In other cases, it’s associated with great emotional stress, like the death of a family member or the loss of a job. The possible link between these unrelated types of trauma is the neurohormonal change that both physical injury and emotional stress can trigger. Psychological processes can change — and can be changed by — alterations in the function of hormone-regulating centers like the hypothalamus and the pituitary and adrenal glands, which in turn can affect the nervous system.
Fibromyalgia’s Other Common Threads
“Fibromyalgia has been associated with all age groups, though women between the ages of 30 and 50 have a higher incidence of the disease,” says Dr. Solitar. While this increased prevalence among younger females suggests a hormonal connection, he says it’s also possible that it’s related to diagnosis. “Women tend to [naturally] be more tender [or sensitive to pain] than men, so if you base your diagnosis on tender points, you’re likely to diagnose more women with fibromyalgia than men.”
Also, fibromyalgia often develops in multiple members of the same family, although it’s not clear if this is the result of genetic or environmental effects. “Family members of people with fibromyalgia seem to be more tender than others,” says Dr. Solitar, “but there isn’t a lot of conclusive genetic research out there.”
In many cases, why fibromyalgia strikes is still largely unknown. “For a lot of patients, we don’t come up with a good explanation for the development of fibromyalgia,” Dr. Solitar notes. “We all get exposed to stress regularly. And while trauma and infections do seem to be a common [fibromyalgia] theme, there are a lot of people who just slowly develop a sense of feeling poorly.”
and its varying array of symptoms often baffle patients and physicians alike. There is still no widely accepted diagnostic blood test or biomarker for the disease, even though sufferers report life-altering physical limitations. Now, new research at the University of Michigan is linking the broad range of fibromyalgia symptoms to a brain molecule called glutamate, opening the door to new treatment options and more precise methods of diagnostic testing.
Fibromyalgia: New Evidence May Help With Diagnosis
Symptoms of fibromyalgia run the gamut from extreme fatigue and flulike body aches to digestive ills and migraine headaches. Due to the absence of a specific quantitative or qualitative test, however, physicians have long been forced to rely on a patient’s self-report to help diagnose this elusive condition. For this reason, some doctors didn’t take the malady seriously.
Groundbreaking research done in 2002 by Daniel Clauw, M.D., professor of medicine and associate dean at the University of Michigan Medical School, provided the first solid biological and physical evidence that fibromyalgia patients really felt intense pain when they said they did. A form of brain imaging called a functional MRI (fMRI) showed that those with fibromyalgia were much more sensitive to pain than those in a control group; similar levels of pain also caused different areas of the brain to light up on the scans of the FM group than those of the control group.
The widespread nature of the chronic pain associated with fibromyalgia — pain not specific to any one group of muscles or joints — is currently under investigation. “Most physicians believed fibromyalgia was a peripheral issue, involving the muscles and joints, because that’s what patients experienced and reported,” says Richard Harris, Ph.D., research investigator in the Department of Internal Medicine’s Rheumatology division at the University of Michigan Medical School, as well as a researcher at the university’s Chronic Pain and Fatigue Research Center; and a colleague of Dr. Clauw. “Findings from our new research suggest that fibromyalgia may be more of a central nervous system condition. This makes it harder for critics to explain away the findings—patients can’t fake an MRI test result.”
Fibromyalia: Glutamate Linked to Pain
Dr. Harris and other University of Michigan researchers found that pain levels in fibromyalgia patients correlated positively with the levels of glutamate, an amino acid and neurotransmitter (brain chemical) responsible for stimulating nerve cells. “When patients were given treatments designed to reduce their pain, glutamate levels went down in a corresponding way,” Harris explains.
Earlier research showed a link between activity in a part of the brain called the insula (insular cortex) and pain in fibromyalgia sufferers. The insula region is also involved with stimuli from muscles and skin in addition to internal sensations like those from the bowel. This association may help explain the higher incidence of digestive problems, such as irritable bowel syndrome, in fibromyalgia. Other fibromyalgia-associated conditions, such as anxiety and migraine headaches, may also be linked to the central nervous system’s involvement, according to Andrew Holman, M.D., rheumatologist and assistant clinical professor of medicine at the University of Washington.
Fibromyalgia: Research Leads to New Medications
New medications are now available for use in treating fibromyalgiasymptoms thanks to this research. “The Food and Drug Administration recently approved pregabalin (Lyrica) and duloxetine (Cymbalta), two medications that both work centrally, as a direct result of the new research,” says Dr. Holman. “Fibromyalgia has its own process, but the problems of the autonomic nervous system that cause Stage 4 sleep deprivation [a symptom of fibromyalgia] originate in the same areas of the brain that are responsible for such issues as bowel motility [which relates to IBS] and the basic fight or flight syndrome [which relates to anxiety symptoms].”
Although these findings validate many of the more subtle symptoms experienced by fibromyalgia patients, more research is needed before fMRI scan testing becomes part of a routine diagnosis, says Harris. Until then, Harris stresses the importance of being aware of your symptoms and managing them appropriately. “Fibromyalgia is not one of those conditions where you can do one thing and then you’re done,” he notes. “It’s a matter of managing symptoms through a multifaceted approach.”
- MedicaFibromyalgia tions
The precise causes of fibromyalgia remain a matter of speculation, so today’s treatments, even those approved by the FDA, are non-specific at best. Many pharmaceutical options, however, are available for treating fibromyalgia’s diverse symptoms, which can range from muscle pain and sleep problems to depression and anxiety.
To date, the antidepressants duloxetine (Cymbalta) and milnacipran (Savella), and pregabalin (Lyrica), an antiseizure medication that’s also used for certain types of pain, are the only prescription medications approved by the FDA specifically for the treatment of fibromyalgia. But doctors employ many other drugs, approved for related conditions, to treat specific symptoms of fibromyalgia. Many of these medications address more than one fibromyalgia-associated problem. As with all drugs, many of the medications listed here have significant side effects and interactions. You should discuss any medicines you are prescribed with your doctor and your pharmacist before taking them. This will help you know what to expect and when you need to report a problem or look for a substitute drug.
Pain relief and improved sleep are the primary goals of fibromyalgia treatment and medications, but doctors also prescribe various drugs to treat depression and fatigue.
The following medications are commonly used in the treatment of fibromyalgia.
Most over-the-counter analgesics don’t work very well for fibromyalgia, because the disorder doesn’t involve much inflammation. Prescription opioids and localized injections can sometimes be helpful, depending on the specific symptoms.
- OTC analgesics. Tylenol (acetaminophen) and nonsteroidal anti-inflammatory drugs (NSAIDs) like ibuprofen (Advil, Motrin) and naproxen (Aleve, Anaprox) may help in some patients. However, they are generally recommended for patients experiencing peripheral pain syndrome (involving muscles and connective tissue and/or the peripheral nervous system as opposed to fibromyalgia, which is a disorder of the central nervous system) in addition to fibromyalgia.
- Opioid therapies. Some relief of pain has been reported with opiates such as tramadol (Ultram), and with the combination of tramadol and acetaminophen (Utracet)— both of which may also relieve sleep problems. While effective for acute severe pain, opioids such as hydrocodone/acetaminophen (Vicodin), propoxyphene/acetaminophen (Darvocet), oxycodone/ acetaminophen (Percocet), and oxycodone (OxyContin) don’t work as well on long-tem chronic pain, generally speaking. Additionally, they carry the risk of addiction and have been linked to other side effects — for example, increasing the body’s sensitivity to pain, as well as to drowsiness and constipation.
- Trigger point injections. Injections of local anesthetics (such as lidocaine and procaine) and/or cortisone (a steroid medication) may help treat painful muscles, tendons, or ligaments and break cycles of pain and muscle spasm.
These medications help regulate certain chemicals in the brain, called neurotransmitters, that are implicated in various fibromyalgia symptoms, including muscle pain, sleep problems, and fatigue. To achieve the best results, they are sometimes used in combination. Those commonly prescribed include:
- Tricyclic antidepressants. Amitriptyline (Elavil, Endep), nortriptyline (Pamelor), and doxepin (Sinequan) as well as the tetracyclic antidepressant trazodone (Desyrel), increase the levels of norepinephrine and serotonin, brain neurotransmitters that affect pain signals and depression, and often have a sedative, sleep-inducing effect.
- Selective serotonin reuptake inhibitors (SSRIs). Included in this group are citalopram (Celexa), escitalopram (Lexapro), fluoxetine (Prozac), sertraline (Zoloft), fluvoxamine (Luvox), and paroxetine (Paxil).
- Selective serotonin and norepinephrine reuptake inhibitors (SSNRIs). This newer class of antidepressants, also known as dual uptake inhibitors, helps regulate the neurotransmitters serotonin and norepinephrine. They include venlafaxine (Effexor), desvenlafaxine (Pristiq), duloxetine (Cymbalta), and Savella (milnacipran).
Medications such as cyclobenzaprine (Flexeril, Cycloflex, and Flexiban), carisoprodol (Soma), and methocarbamol (Skelex) are often prescribed to treat painful muscle spasms; they are usually used for short-term relief.
This class of drugs is used for fibromyalgia because these medications also help treat neuropathic pain, which occurs when nerves are overexcited and need to be desensitized. Drugs in this category include pregabalin (Lyrica), as well as carbamazepine (Carbatrol, Epitol, Equetro, Tegretol, and Tegretol-XR) and gabapentin (Gabarone, Neurontin).
Restful sleep is critical for easing the symptoms of fibromyalgia. If other medications (specifically, muscle relaxants and antidepressants) are not effective, doctors may prescribe short-term sleep aids such as zolpidem (Ambien), zaleplon (Sonata), and eszopiclone (Lunesta), which work by slowing brain activity to permit sleep. Such medications often lose their effectiveness over the long term, however.
Some doctors are now prescribing medications used for attention deficit hyperactivity disorder, such as methylphenidate (Ritalin), dextroamphetamine sulfate (Dexedrine), and modafinil (Provigil) to ease symptoms of fatigue and “brain fog” (difficulty thinking and concentrating) that patients with fibromyalgia often experience..
On the horizon
Among new medications being researched for the treatment of fibromyalgia is sodium oxybate (Xyrem), also known as GHB. This central nervous system depressant is currently approved for the treatment of narcolepsy, but has shown promise for pain relief and improved functioning in patients with fibromyalgia. An application for approval was submitted to the FDA on December 15, 2009.
Finally, in addition to prescription medications, doctors often recommend thatother pain management therapies be explored. Among the most effective are therapeutic massage and myofascial release therapy, a specialized technique used to ease tension in the body, which can help relieve muscle discomfort and reduce spasms..