My mother has experienced widespread chronic pain, fatigue and brain fog, among other symptoms, for years. After much uncertainty, she received a final diagnosis: Fibromyalgia syndrome (FMS).
In addition to pain and fatigue, those with FMS can experience unrefreshing sleep, headaches, irritable bowel syndrome, cognitive dysfunction, depression, anxiety and environmental sensitivities. Patients also report disrupted relationships, social isolation, reduced activities of daily living and career loss.
Globally, FMS prevalence is estimated to be between 2% and 6%, and in the UK, prevalence is estimated at 5.4%, equivalent to over 3.7 million people.
While the exact cause of FMS is unknown, possible contributing factors include genetics, infections and physical or emotional trauma. Women between the ages of 30 and 50 with familial history are most at risk of the condition.
My mother hadn’t heard much about the condition at the time of her diagnosis and was devastated when told that FMS is incurable. Different doctors she has spoken to over the years have given varying opinions on the disease, some suggesting that she could try different painkillers and others implying that there isn’t much to be done.
Over the years that have followed, a loose pattern has emerged: once in a blue moon she will wake up feeling energized and ready to take on the day. She will go to work, perhaps do some housework and make a meal. For the following three days or more, she will barely be able to get up in the morning.
Most days, she will exist somewhere between the two extremes, where she can ignore her pain and fatigue for a few hours and then is unable to go on without some sleep.
Many people who receive this diagnosis, my mother included, have tried everything to combat their symptoms, from painkillers to exercise and home remedies. None of which seem to have had any lasting impact.
In this article, we explore treatment options for FMS, what current research can tell us about the disease and what the future of FMS research could look like.
Fibromyalgia management: Medicines and lifestyle changes
Receiving a diagnosis is an essential step towards managing the condition. Unfortunately, this can be an uphill battle.
“Diagnosis of fibromyalgia is related to identification of the cardinal symptoms and elimination of other clinical conditions that could be responsible for similar symptoms. There is currently no biochemical or physical test that reliably identifies fibromyalgia. As a consequence, the lack of a specific approach can lead to under or over interpretation and a delay in diagnosis,” said Dr. Kim Lawson, an independent consultant and chair of the medical advisory board to Fibromyalgia Action UK.
Lawson has spent over 20 years researching FMS and attempting to improve patients’ lives. In the final year of my undergraduate degree, inspired to learn more about the condition following my mother’s recent diagnosis, I chose to do my dissertation on the treatments for FMS with Lawson, who was a senior lecturer in pharmacology at Sheffield Hallam University at the time.
While there is no single treatment to alleviate all the symptoms of FMS, there are several options available, as described by Lawson: “Treatment involves a combination of exercise, coping techniques (such as cognitive behavioral therapy (CBT) or mindfulness) and medication. Medication can include amitriptyline, duloxetine, pregabalin, gabapentin or tramadol alone or combined. The effectiveness of the available treatments is individualized and very dependent on the patient’s medical history.”
Table 1: Methods of symptom management commonly used by FMS patients.
Medicines
Non-steroidal anti-inflammatory drugs (NSAIDs)
NSAIDs are one of the most commonly used drugs in FMS patients. In a cross-sectional study, while 41% of patients reported use of NSAIDS, of those that discontinued use, 83% did so because they had no perceived effect on pain.
Opioids
According to a 2020 meta-analysis, the prevalence of long-term opioid use was 24% in FMS patients. The CDC guidelines do not recommend the use of such drugs for chronic pain due to the likelihood that the benefits are unlikely to outweigh the risks (e.g., abuse, overdose and heart attacks) regardless of previous nonpharmacologic and nonopioid pharmacologic therapies used.
Antidepressants
Duloxetine and milnacipran are FDA-approved for the treatment of FMS. Duloxetine is more effective than placebo in reducing pain regardless of dose. Milnacipran is effective at reducing FMS symptoms but can cause nausea, headache, hypertension, sinusitis and suicidal thinking. Amitriptyline is associated with improvements in sleep, quality of life, fatigue and pain.
Anti-seizure
Pregabalin is effective at reducing pain for 10% of patients with FMS. Another commonly prescribed medication, Gabapentin, was only found to reduce pain by 30% in 49% of participants, compared with 31% with placebo.
Lifestyle changes
Exercise
Studies suggest that mixed exercise has the potential to improve quality of life, physical function and fatigue, but improvements may be small and clinically unimportant for some participants.
Dietary changes
Limited studies have been conducted on the impacts of gluten-free and anti-inflammatory diets on FMS symptoms, however, plant-based diets have been seen to provide some improvements to pain.
Stress management techniques
At least six months of cognitive behavioral therapies can provide a small incremental benefit in reducing pain, negative mood and disability.
Alternative therapies
Acupuncture
When combined with other treatments, acupuncture appears to be effective in the treatment of FMS for reducing pain in the short term.
Dry needling
Dry needling is the practice of inserting thin monofilament needles into myofascial trigger points (MTrPs) -hyperirritable points located within a taut band of skeletal muscle that cause referred pain and local tenderness, either spontaneously, with movement or in response to compression. Patients have reported short-term reductions in trigger point pain and improvements in anxiety, depression and fatigue symptoms, quality of life and sleep following treatment.
Myofascial release
Myofascial release involves the gentle massaging of MTrPs. Patients have reported improvements in pain intensity and the impact of other FMS symptoms.
Chronic pain in FMS
The reason FMS is so difficult to treat is partly due to the type of pain experienced. In contrast to nociceptive pain (caused by damage to body tissue) and neuropathic pain (caused by damage or malfunction of the nervous system), “nociplastic pain classifies altered processing within the pain pathways with an absence of evidence of actual or threatened tissue damage,” explained Lawson.
Nociplastic pain
The International Association for the Study of Pain defines nociplastic pain as: pain that arises from altered nociception despite no clear evidence of actual or threatened tissue damage causing the activation of peripheral nociceptors or evidence for disease or lesion of the somatosensory system causing the pain.
Dr. Claudia Sommer is a professor of neurology at the University of Würzburg. Sommer’s research has contributed significantly to the understanding of how pain is processed, a crucial requirement for developing better treatment strategies for FMS. “Changes in the function and anatomy of the nociceptive system have been described using a variety of techniques. For example, fibromyalgia patients may have reduced skin innervation and diminished nerve fibers in the cornea. They also have increased spontaneous activity and C-fiber excitability compared to healthy people. How these changes impact the fibromyalgia symptoms and how the central nervous system (CNS) and peripheral nervous system (PNS) pathophysiologically interact are questions for ongoing research,” Sommer said.
“Pharmacological agents with moderate efficacy are compounds that we also use for treating neuropathic pain. They alleviate pain in some patients. However, the underlying pathophysiology of fibromyalgia pain is likely different to that of neuropathic pain, and other pharmaceuticals addressing these exact mechanisms should be used,” said Sommer. Unfortunately, the development of such drugs is difficult when the pathophysiology of FMS pain is not completely understood.
For Sommer, the ultimate goal is a better understanding of the mechanisms at play in FMS, leading to the development of pathophysiology-oriented disease-modifying treatments.
Is fibromyalgia an autoimmune disease?
A study published in the Journal of Clinical Investigation suggests that antibodies may be a more suitable target for drugs. According to the research, pain sensitivity in FMS is caused by antibodies increasing the activity of pain-sensing nerves.
Co-senior author of the study, Dr. David Andersson, a professor of neuroscience at King’s College London, said: “While the most widely held view is that fibromyalgia originates in the brain, our research challenges this, and provides evidence that it is associated with antibodies.”
In the study, the researchers took antibodies from donors with FMS and injected them into mice. “These mice became hypersensitive to touch and cold temperature, reduced their paw grip strength and reduced their movement. We also noted that pain-sensing nerves became more active, demonstrating that the antibodies act throughout the body, rather than in the brain, and that tenderness and hypersensitivity are caused by the heightened activity of the pain-sensing nerve fibers,” said Andersson.
Antibodies taken from healthy donors had no impact on mice.
Mice injected with FMS antibodies recovered after a few weeks when the antibodies had been cleared from their system. “Our results show that the immune system is responsible for fibromyalgia symptoms, and that new treatments that remove the antibodies from the blood, or that prevent their effects are likely to be effective against fibromyalgia,” he said.
Andersson’s current research is focused on the link between FMS and rheumatic disease. FMS is much more common in people living with rheumatic disease, with around 20-30% of patients with rheumatic diseases being affected. “We are currently investigating whether the same principles that we previously identified in patients that “only” live with fibromyalgia also hold true in patients with a rheumatic disease, like rheumatoid arthritis or ankylosing spondylitis. Since pain and fibromyalgia are often not helped by the available treatments, it is important to us to establish whether autoantibodies are responsible as this can have a major impact on quality of life and will guide future treatment,” he said.
Modern treatments usually control the damaging inflammation in rheumatic diseases well, but they aren’t effective when it comes to pain reduction. “We anticipate that treatments that lower the levels of the antibodies responsible will be effective against fibromyalgia in rheumatic patients,” explained Andersson. An ongoing study will determine whether this is correct, involving patients diagnosed with either rheumatoid arthritis, ankylosing spondylitis or Behḉet’s disease.
Novel treatment approaches
Although no single treatment is effective for all FMS patients, research into novel approaches is ongoing. “Novel and different pharmacological approaches currently being explored include cannabinoid and cannabis-based medications, orexin receptor antagonists, immunoglobulin antibodies (e.g., rozanolixizumab), N-methyl-D-aspartate receptor modulators and psilocybin derivatives which exhibit serotonin receptor agonist properties (e.g., TRP-8802),” said Lawson.
Cannabis
A small study published in Pain Medicine found that tetrahydrocannabinol (THC)-rich cannabis oil significantly reduced scores for areas related to FMS when compared to placebo. In the study, patients gave a score of 0-10 for areas including physical function, job ability, pain, fatigue, morning tiredness, anxiety and depression in a fibromyalgia impact questionnaire (FIQ), with higher scores indicating greater impact on quality of life. Mean scores reduced from 75.5 to 30.5 in the cannabis group, and 70.2 to 61.2 in the placebo group.
Another study found that while cannabis had no significant impact on spontaneous pain scores over placebo, specific strains of cannabis with a high THC content increased tolerance to pressure.
Orexin receptor antagonists
Suvorexant, an orexin receptor antagonist, was able to increase total sleep time, reduce wake after sleep onset and reduce next-day pain sensitivity in FMS patients with insomnia. Orexin receptor antagonists penetrate the blood–brain barrier and block the binding of wake-promoting neuropeptides, reducing wake drive.
N-methyl-d-aspartate receptor modulation
Activation of the N-methyl-d-aspartate receptor (NMDAR) increases the sensitivity of spinal cord and brain pathways that process sensory information, including pain. There is evidence of increased NMDAR activity in FMS patients. One NMDAR antagonist, ketamine, has seen success in reducing pain intensity for some patients.
Another NMDAR antagonist, memantine, was found to significantly reduce pain, increase pain threshold, and improve global function, mood and quality of life when compared to placebo.
Alternative treatment approaches
Alongside ongoing research into pharmaceutical treatments, alternative techniques are also being investigated. “Pain is not the only problem in fibromyalgia. Unrefreshed sleep, autonomic symptoms and cognitive symptoms may all be present and might need to be treated by addressing different targets. This is probably why, until now, nonpharmacological treatment has been the most effective in targeting the symptoms of fibromyalgia,” said Sommer.
Acceptance and commitment therapy (ACT)
While CBT seeks to reduce or change distressing pain-related thoughts, emotions, sensations, or memories, ACT aims to promote the acceptance of challenges including pain, illness and anxiety to improve psychological flexibility.
In a systematic review of six studies, Eastwood et al. found that ACT improved scores for health-related quality of life and pain acceptance. There was also improvement in anxiety, depression, pain, disability and fatigue scores. Online ACT has also been found to improve pain and anxiety.
Photobiomodulation (PBM)
PBM, previously known as low-level laser therapy, is a non-invasive treatment in which light energy penetrates tissue and interacts with chromophores located in cells, resulting in molecular, cellular and tissue alterations. PBM is currently used for pain relief, inflammation and sport injury treatment.
The therapy has been shown to be beneficial for conditions including osteoarthritis, chronic neck pain and central nervous diseases such as Parkinson’s disease. In a clinical trial with FMS patients, a significant reduction in pain and an improvement in quality of life was observed after four weeks of whole-body treatment with PBM.
A meta-analysis of published randomized controlled trials evaluating the effect of PBM on FMS found that PBM alone did not show benefit. However, when combined with exercise therapy, patients experienced reduced severity of pain, number of tender points and fatigue over those receiving exercise therapy alone.
Social contact
Support networks can positively impact the physical, mental and social wellbeing of women with FMS. “Social support may help reappraise pain, reduce pain-related thoughts and lower perceived pain intensity, which correlates with increased positive emotions and reduced depression. A lack of support, conversely, can increase pain,” said Sommer.
In a recent study into a different chronic pain condition, complex regional pain syndrome, Sommer and colleagues found that “solicitous support increased pain relief, especially in men, while emotional support helped reduce pain in women. More research is needed to explore these gender differences and further understand how different types of social support impact pain, also in fibromyalgia,” Sommer said.
Other areas currently under investigation include transcutaneous electrical nerve stimulation, hydrotherapy, virtual reality distraction therapy, graded exercise therapy and yoga therapy, among others.
FMS remains a complex and often misunderstood condition, affecting millions worldwide. While there is no definitive cure, advances in research and treatment options continue to offer hope for better management and improved quality of life.
As awareness grows and more healthcare providers are better equipped to recognize the symptoms, those living with FMS will hopefully receive the essential support they deserve. Continued collaboration between patients, researchers and healthcare professionals will be key in unlocking further insights into this chronic condition.
Useful resources:
Fibromyalgia Action UK booklets.
Pain Concern’s Self-Management Navigator Tool.
Versus Arthritis’ Fibromyalgia booklet.
