Fibromyalgia (FM) is a complex disorder characterised by chronic widespread musculoskeletal pain. In addition, other symptoms such as fatigue, cognitive disturbances, anxiety and depression, headaches and migraines, burning/prickling of the extremities, and gastrointestinal syndromes (IBS, GERD), dry eyes, difficulty breathing or swallowing, and palpitations often accompany FM1. As a result, the condition has immense societal impact as measured by work absenteeism, decreased work productivity, disability and injury compensation, and over-utilisation of healthcare resources2.
FM affects 2–5% of the adult population in the United States2, with a similar incidence in Australia, and is predominantly diagnosed in young to middle-aged women3-5. About 75% of individuals with FM remain undiagnosed and it takes on average up to 5 years for affected individuals to obtain a diagnosis from time of onset of initial symptoms6.
Fibromyalgia is a chronic pain disorder of unknown cause7. There is no evidence of tissue inflammation despite symptoms of soft tissue pain1. Some studies have shown a genetic predisposition for fibromyalgia though there is no documentation pinpointing a particular gene8. There is also no evidence of any single event that triggers the condition, but multiple physical and/or emotional stressors, including viral infections, as well as long-standing emotional and/or physical stress, may trigger or aggravate the condition2, 9.
Ongoing research suggests that FM is a pain regulation disorder and is classified as a form of central sensitisation syndrome10, where the individual is not able to process pain in the brain. With repetitive adverse stimuli, FM patients experience higher than normal increases in the perceived sensitivity to pain, with an apparent deficiency in the normal analgesic systems that operate in the central nervous system (CNS). Functional magnetic resonance imaging of FM patients has identified differences in activation of areas of the brain which respond to pain1. In addition, FM patients often have detectable elevated levels of excitatory pain (nociceptive) neurotransmitters such as glutamine, low levels of analgesic (anti-nociceptive) neurotransmitters such as serotonin and norepinephrine, prolonged hypersensitivity to pain, and dysregulation of dopamine1.
Treatment options for FM
Current treatment options for fibromyalgia patients are limited and hampered by lack of consistent, evidence-based management guidelines2. Patient management requires input from many different health care providers, including medical, allied health, and complementary and alternative medicine practitioners3. Since pain processing requires transmission from peripheral tissues to the brain, it can be modified by both internal and external processes. Thus, physical and psychological interventions can help to reduce the perception of pain in affected individuals. Interventions include patient education, relaxation, stress reduction, good sleep hygiene, exercise, and cognitive behavioural therapy (CBT)11-13. For patients who do not respond to these management options, pharmacological interventions include selective serotonin reuptake inhibitors (SSRIs), serotonin norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants, and anticonvulsants, which work by modulating the neurochemical pain pathways present in the brain14-16. There is limited evidence for the effectiveness of analgesics (particularly opioids which are discouraged for FM)17, 18, NSAIDs and anti-inflammatory drugs1, 2, 19. Unfortunately, treatment often fails to lead to adequate recovery7, 8, 10, 20 and therefore patients often seek alternative therapies.
Potential treatments for FM
Some studies have shown benefits with neuromodulation techniques like transcranial stimulation, occipital and C2 nerve stimulation and transcutaneous electrical nerve stimulation9, but the evidence is still inconclusive and further studies will be needed to show their efficacy in FM1, 21.
There is also some evidence for complementary therapies such as acupuncture1, 22-24, as well as for thermal therapies, hyperbaric oxygen therapy, laser and phototherapy21, but robust studies are still lacking.
Although there is still limited evidence to support its role in the treatment of FM, there is some evidence to suggest that medicinal cannabis could be an effective alternative for the treatment of FM symptoms25. The endocannabinoid system (ECS) is involved in the regulation of pain sensation and regulates actions at all stages of pain processing pathways in the central nervous system26. ECS components have been found in pain circuits from peripheral sensory nerve endings up to the brain27. For example, the cannabinoid 1 (CB1) receptor is involved in the attenuation of synaptic transmission27 and in controlling the release of neurotransmitters such as dopamine, noradrenaline, glutamate, GABA, serotonin and acetylcholine28, 29. The activation of CB1 receptors in the brain modulates nociceptive thresholds and regulates the balance between excitatory and inhibitory neurotransmitters29, 30. Deficiency in the ECS has been proposed as a mechanism contributing to FM but clear clinical evidence to confirm this is still lacking31. In the US, a recent survey found that cannabidiol (CBD), the main non-psychoactive cannabinoid found in cannabis, is commonly used by individuals with FM, with many reporting improvements across numerous FM-related symptoms32. A systematic review which included 3 randomised controlled trials, 6 observational studies, and one study that compared the management of chronic pain patients with FM patients, concluded that cannabis was safe and well tolerated and that it could be beneficial for some patients33, although these findings were not been corroborated by another review34. An observational study found that adjunctive medicinal cannabis offered a possible clinical advantage in FM patients, especially in those with sleep problems35, and a randomised, double-blind, placebo-controlled clinical trial in 17 women with FM showed a significant decrease in Fibromyalgia Impact Questionnaire score in comparison with the placebo group, although the number of participants was too small to reach a definitive conclusion36. Evidence supporting the use of cannabis in fibromyalgia is being gathered in a couple of current clinical trials overseas (NCT04729179, NCT04239469), but many more studies will be needed to determine effectiveness. In conclusion, while the current evidence is still limited, emerging data do suggest a positive effect of cannabis in fibromyalgia. However, it is important to note that medicinal cannabis use is not without risks, including psychiatric and cognitive. Further research will be required to define efficacy, safety, appropriate patient selection and treatment regimens37.
- Bhargava J, Hurley JA. Fibromyalgia.StatPearls. Treasure Island (FL): StatPearls Publishing. Copyright © 2020, StatPearls Publishing LLC.; 2020.
- Hackshaw KV. The Search for Biomarkers in Fibromyalgia. Diagnostics (Basel). 2021;11(2).
- Guymer E, Littlejohn G. Fibromyalgia. Australian Family Physician. 2013;42:690-4.
- Vincent A, Lahr BD, Wolfe F, Clauw DJ, Whipple MO, Oh TH, et al. Prevalence of fibromyalgia: a population-based study in Olmsted County, Minnesota, utilizing the Rochester Epidemiology Project. Arthritis Care Res (Hoboken). 2013;65(5):786-92.
- Jones GT, Atzeni F, Beasley M, Flüß E, Sarzi-Puttini P, Macfarlane GJ. The prevalence of fibromyalgia in the general population: a comparison of the American College of Rheumatology 1990, 2010, and modified 2010 classification criteria. Arthritis Rheumatol. 2015;67(2):568-75.
- Walitt B, Katz RS, Bergman MJ, Wolfe F. Three-Quarters of Persons in the US Population Reporting a Clinical Diagnosis of Fibromyalgia Do Not Satisfy Fibromyalgia Criteria: The 2012 National Health Interview Survey. PLOS ONE. 2016;11(6):e0157235.
- Schmidt-Wilcke T, Clauw DJ. Fibromyalgia: from pathophysiology to therapy. Nat Rev Rheumatol. 2011;7(9):518-27.
- Buskila D, Sarzi-Puttini P. Biology and therapy of fibromyalgia. Genetic aspects of fibromyalgia syndrome. Arthritis Res Ther. 2006;8(5):218.
- Brighina F, Curatolo M, Cosentino G, De Tommaso M, Battaglia G, Sarzi-Puttini PC, et al. Brain Modulation by Electric Currents in Fibromyalgia: A Structured Review on Non-invasive Approach With Transcranial Electrical Stimulation. Front Hum Neurosci. 2019;13:40.
- Pomares FB, Funck T, Feier NA, Roy S, Daigle-Martel A, Ceko M, et al. Histological Underpinnings of Grey Matter Changes in Fibromyalgia Investigated Using Multimodal Brain Imaging. J Neurosci. 2017;37(5):1090-101.
- Bernardy K, Füber N, Köllner V, Häuser W. Efficacy of cognitive-behavioral therapies in fibromyalgia syndrome – a systematic review and metaanalysis of randomized controlled trials. J Rheumatol. 2010;37(10):1991-2005.
- Davis MC, Zautra AJ. An online mindfulness intervention targeting socioemotional regulation in fibromyalgia: results of a randomized controlled trial. Ann Behav Med. 2013;46(3):273-84.
- Busch AJ, Barber KA, Overend TJ, Peloso PM, Schachter CL. Exercise for treating fibromyalgia syndrome. Cochrane Database Syst Rev. 2007(4):Cd003786.
- Arnold LM, Choy E, Clauw DJ, Oka H, Whalen E, Semel D, et al. An evidence-based review of pregabalin for the treatment of fibromyalgia. Curr Med Res Opin. 2018;34(8):1397-409.
- Welsch P, Üçeyler N, Klose P, Walitt B, Häuser W. Serotonin and noradrenaline reuptake inhibitors (SNRIs) for fibromyalgia. Cochrane Database Syst Rev. 2018;2(2):Cd010292.
- Ottman AA, Warner CB, Brown JN. The role of mirtazapine in patients with fibromyalgia: a systematic review. Rheumatol Int. 2018;38(12):2217-24.
- Fitzcharles MA, Faregh N, Ste-Marie PA, Shir Y. Opioid use in fibromyalgia is associated with negative health related measures in a prospective cohort study. Pain Res Treat. 2013;2013:898493.
- Peng X, Robinson RL, Mease P, Kroenke K, Williams DA, Chen Y, et al. Long-term evaluation of opioid treatment in fibromyalgia. Clin J Pain. 2015;31(1):7-13.
- Ngian GS, Guymer EK, Littlejohn GO. The use of opioids in fibromyalgia. Int J Rheum Dis. 2011;14(1):6-11.
- Staud R. Abnormal pain modulation in patients with spatially distributed chronic pain: fibromyalgia. Rheum Dis Clin North Am. 2009;35(2):263-74.
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- Mist SD, Firestone KA, Jones KD. Complementary and alternative exercise for fibromyalgia: a meta-analysis. J Pain Res. 2013;6:247-60.
- Karatay S, Okur SC, Uzkeser H, Yildirim K, Akcay F. Effects of Acupuncture Treatment on Fibromyalgia Symptoms, Serotonin, and Substance P Levels: A Randomized Sham and Placebo-Controlled Clinical Trial. Pain Med. 2018;19(3):615-28.
- Zhang XC, Chen H, Xu WT, Song YY, Gu YH, Ni GX. Acupuncture therapy for fibromyalgia: a systematic review and meta-analysis of randomized controlled trials. J Pain Res. 2019;12:527-42.
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