Fibromyalgia is a complex and often misunderstood disorder characterized by widespread musculoskeletal pain, fatigue, sleep disturbances, and memory and mood issues. Despite its prevalence, affecting millions worldwide, the exact causes of fibromyalgia remain elusive, making diagnosis and treatment challenging for healthcare providers. This article aims to provide a systematic and complete understanding of fibromyalgia, from its symptoms and causes to diagnosis, treatment, and coping strategies.
Fibromyalgia is considered a rheumatic condition, similar to arthritis, in that it impairs the joints and/or soft tissues and causes chronic pain. However, unlike arthritis, fibromyalgia does not cause inflammation or damage to the joints, muscles, or other tissues. Instead, it is characterized by pain throughout the body and an increased sensitivity to pain.
The primary symptom of fibromyalgia is widespread pain, described as a constant dull ache that has lasted for at least three months. This pain occurs on both sides of the body and above and below the waist. Other common symptoms include:
• Fatigue: Patients often awaken tired, even after sleeping for long periods. Sleep is frequently disrupted by pain, and many patients have other sleep disorders, such as sleep apnea and restless legs syndrome.
• Cognitive difficulties: Known as “fibro fog,” this symptom impairs the ability to focus, pay attention, and concentrate on mental tasks.
• Emotional symptoms: Anxiety and depression are common among fibromyalgia patients.
Other symptoms can include headaches, irritable bowel syndrome, numbness or tingling in the hands and feet, painful menstrual periods, and temperature sensitivity.
The exact cause of fibromyalgia is unknown, but it’s likely a combination of genetic, environmental, and psychological factors.
• Genetic predisposition: Fibromyalgia often runs in families, suggesting a genetic component.
• Infections: Some illnesses appear to trigger or aggravate fibromyalgia.
• Physical or emotional trauma: Post-traumatic stress disorder (PTSD) has been linked to fibromyalgia.
• Other disorders: Rheumatoid arthritis, lupus, and other autoimmune diseases are often associated with fibromyalgia.
There are no specific laboratory tests for diagnosing fibromyalgia. Instead, the diagnosis is made based on a comprehensive examination, which includes a medical history, physical examination, and sometimes, blood tests to rule out other conditions. The American College of Rheumatology (ACR) criteria for fibromyalgia diagnosis include widespread pain lasting at least three months and the presence of other symptoms such as fatigue and cognitive disturbances.
While there is no cure for fibromyalgia, a variety of treatments can help manage symptoms. Treatment plans often include a combination of:
• Medications: Pain relievers, antidepressants, and anti-seizure drugs are often prescribed to manage symptoms.
• Physical therapy: Tailored exercise programs can improve strength, flexibility, and stamina.
• Counseling: Cognitive behavioral therapy (CBT) can help manage the emotional symptoms associated with fibromyalgia.
• Lifestyle changes: Regular exercise, stress management techniques, and healthy sleep habits can significantly reduce symptoms.
Living with fibromyalgia requires a holistic approach to manage both physical and emotional health. Strategies for coping with the disorder include:
• Educating oneself and others about the condition.
• Seeking support from fibromyalgia support groups and healthcare providers.
• Establishing a healthy and balanced routine.
• Practicing mindfulness and relaxation techniques to reduce stress.
Fibromyalgia is a challenging condition that affects every aspect of a patient’s life. While the path to diagnosis and effective management can be difficult, advances in our understanding of the disorder have led to better treatment options and coping strategies. Through a combination of medical treatment, lifestyle adjustments, and support, individuals with fibromyalgia can lead fulfilling lives despite their symptoms. As research continues, there is hope for new insights into the causes and treatments of this complex condition.
GENETIC FACTORS INVOLVED IN FIBROMYALGIA
The role of genetic factors in fibromyalgia suggests a significant hereditary component to the disorder, although the precise genetic underpinnings are complex and not fully understood. Research indicates that fibromyalgia is often seen in families, with individuals having a higher likelihood of developing the condition if a close relative also has it. This familial aggregation points towards a genetic predisposition to fibromyalgia. However, it’s important to note that fibromyalgia is a multifactorial condition, meaning that both genetic predispositions and environmental triggers contribute to its onset. Here is a detailed look into the genetic factors associated with fibromyalgia:
• Family Studies: Studies have shown that immediate family members of people with fibromyalgia are at a higher risk of developing the condition themselves, suggesting a genetic link. The prevalence of fibromyalgia among first-degree relatives of affected individuals is significantly higher compared to the general population.
• Twin Studies: Research involving twins has provided insights into the genetic component of fibromyalgia. These studies suggest that there is a higher concordance rate for fibromyalgia among monozygotic (identical) twins than dizygotic (fraternal) twins, indicating a genetic influence.
While there is no single “fibromyalgia gene,” several genetic variants have been associated with an increased risk of developing the condition:
• Serotonin-Related Genes: Variants in genes involved in the serotonin pathway have been linked to fibromyalgia. Serotonin is a neurotransmitter that plays a crucial role in mood regulation, pain perception, and sleep. Altered levels of serotonin are thought to contribute to the symptoms of fibromyalgia.
• Catechol-O-Methyltransferase (COMT) Gene: The COMT gene, which is involved in the breakdown of catecholamines (a group of neurotransmitters that includes dopamine and norepinephrine), has been studied in relation to pain sensitivity and fibromyalgia. Certain polymorphisms in the COMT gene have been associated with increased pain sensitivity and a higher risk of fibromyalgia.
• Dopamine-Related Genes: Because dopamine plays a key role in how the brain processes pain, variants in genes related to dopamine function may influence the risk of developing fibromyalgia.
Epigenetic mechanisms, which involve changes in gene expression without altering the DNA sequence, may also play a role in fibromyalgia. These changes can be influenced by environmental factors and might explain how stress, trauma, and infections could trigger fibromyalgia in genetically predisposed individuals. Epigenetic modifications can affect pain perception and inflammation pathways, contributing to the symptoms of fibromyalgia.
The interaction between genetic predispositions and environmental factors (such as physical or emotional stress, infections, and lifestyle) is crucial in understanding the development of fibromyalgia. Individuals with a genetic predisposition may be more likely to develop fibromyalgia following specific environmental triggers.
The genetic factors involved in fibromyalgia highlight the complexity of the condition. While significant strides have been made in identifying genetic associations with fibromyalgia, more research is needed to fully understand the genetic contributions and their interactions with environmental factors. Understanding these genetic underpinnings may lead to better-targeted therapies and interventions for those suffering from fibromyalgia in the future.
PATHOPHYSIOLOGY OF FIBROMYALGIA
The pathophysiology of fibromyalgia is complex and not fully understood, encompassing multiple systems and processes at the molecular level. It is characterized by widespread pain, fatigue, sleep disturbances, and cognitive difficulties, among other symptoms. Research suggests that fibromyalgia arises from a combination of genetic, neuroendocrine, and psychosocial factors, leading to abnormalities in pain processing by the central nervous system (CNS).
Central sensitization is considered a cornerstone in the pathophysiology of fibromyalgia. It refers to an increased sensitivity to pain in the brain and spinal cord, resulting from changes in neurotransmitter levels and receptor activity. This heightened sensitivity means that pain signals are amplified, and non-painful stimuli may be perceived as painful (allodynia).
There are altered levels of various neurotransmitters involved in pain regulation, including serotonin, norepinephrine, and dopamine. For instance, reduced levels of serotonin and norepinephrine can lead to an increased perception of pain. Substance P, a neuropeptide associated with pain perception, has been found in elevated levels in the cerebrospinal fluid of fibromyalgia patients.
Hypothalamic-Pituitary-Adrenal (HPA) Axis plays a critical role in the stress response and regulation of various body processes, including digestion, the immune system, mood and emotions, and energy storage and expenditure. In fibromyalgia, the HPA axis may be dysregulated, leading to altered cortisol levels, which can affect pain perception and contribute to symptoms.
As mentioned previously, certain genetic polymorphisms, particularly in genes related to neurotransmitter systems (e.g., COMT, MAO), have been associated with fibromyalgia. These genetic variations may influence individuals’ susceptibility to developing fibromyalgia by affecting pain perception and stress response systems. Emerging research suggests that neuroinflammation could play a role in fibromyalgia. Inflammatory cytokines (small proteins important in cell signaling) can affect neurotransmitter systems and pain pathways, potentially contributing to the symptoms of fibromyalgia. However, unlike inflammatory diseases like rheumatoid arthritis, direct evidence of systemic inflammation in fibromyalgia is lacking, and the concept of neuroinflammation is more subtle, referring to inflammation within the nervous system.
The dysfunction in neurotransmitter systems leads to an imbalance that affects pain perception, mood, sleep, and cognitive functions. For example, glutamate, an excitatory neurotransmitter, has been found in higher concentrations in certain brain regions of fibromyalgia patients, which could contribute to central sensitization.
There is evidence of autonomic nervous system dysfunction in fibromyalgia, including altered heart rate variability and skin conductance, which may be related to the regulation of stress responses and pain perception.
The pathophysiology of fibromyalgia involves a complex interplay of genetic, biochemical, and physiological factors leading to altered pain perception and processing. Central sensitization, neurotransmitter imbalances, HPA axis dysfunction, neuroinflammation, and autonomic nervous system dysfunction are all components that contribute to the condition’s symptoms. Understanding these mechanisms is crucial for developing targeted therapies to manage fibromyalgia effectively. However, given its multifaceted nature, treatment often requires a multidisciplinary approach addressing both physical and psychological aspects.
ENZYME SYSTEMS INVOLVED IN FIBROMYALGIA
The discussion of enzymes in the context of fibromyalgia involves understanding the broader biochemical and physiological processes that may contribute to the condition’s symptoms. While fibromyalgia is not directly caused by enzyme deficiencies or abnormalities, certain enzymes related to pain perception, muscle metabolism, and the stress response might play roles in the symptomatology of fibromyalgia. Research in this area is still evolving, and much of the information comes from studies exploring the complex interactions between neurotransmitters, hormones, and immune responses. Here are a few key enzymes and related processes that have been studied in relation to fibromyalgia:
Catechol-O-Methyltransferase (COMT) is involved in the breakdown of catecholamines, which are neurotransmitters important for the stress response and pain perception. Variants of the COMT gene that reduce enzyme activity have been associated with increased pain sensitivity, a common symptom in fibromyalgia . •Substrates: Catecholamines (dopamine, norepinephrine, and epinephrine) • Activators: Magnesium has been shown to play a role in the optimal activity of COMT. • Inhibitors: Certain genetic polymorphisms can result in reduced activity of the COMT enzyme, leading to increased pain sensitivity and possibly contributing to the symptoms of fibromyalgia.
Monoamine Oxidase (MAO) could influence pain perception and mood, contributing to the symptoms of fibromyalgia by altering the levels of serotonin and norepinephrine due to changes in MAO activity . • Substrates: Monoamines (serotonin, norepinephrine). • Activators: Certain types of antidepressants, known as MAO inhibitors (MAOIs), actually inhibit the activity of MAO to increase the levels of its substrates. • Inhibitors: MAOIs, such as phenelzine, are used to treat depression and anxiety disorders by inhibiting MAO activity, which could have implications for managing fibromyalgia symptoms related to mood and pain.
Cyclooxygenase (COX) plays a role in pain and inflammation pathways, which is relevant to symptom management, even though fibromyalgia is not characterized by inflammation in the same way as rheumatoid arthritis. • Substrates: Arachidonic acid. • Activators: Inflammatory signals. • Inhibitors: Nonsteroidal anti-inflammatory drugs (NSAIDs) like ibuprofen and aspirin inhibit COX activity, potentially reducing pain and inflammation.
Nitric Oxide Synthase (NOS) produces Nitric oxide (NO), which has various roles in the body, including the modulation of pain. Altered NO pathways have been implicated in the pathophysiology of fibromyalgia, although the exact relationship remains unclear. • Substrates: L-arginine. • Activators: Calcium, calmodulin. • Inhibitors: L-NMMA (NG-monomethyl-L-arginine), a competitive inhibitor
.
While these enzymes and their pathways are not exclusively responsible for fibromyalgia, understanding their roles in pain perception, muscle metabolism, and stress responses provides insight into the complex biological underpinnings of the condition. Future research may uncover more about how these enzymes contribute to fibromyalgia and how targeting these pathways could offer new avenues for treatment. However, it’s important to note that fibromyalgia’s etiology is multifactorial, involving genetic, environmental, and psychosocial factors, and thus cannot be reduced to alterations in enzyme activities alone.
ROLE OF HORMONES
The role of hormones in fibromyalgia encompasses their involvement in pain regulation, stress response, sleep-wake cycles, and mood regulation. Hormonal imbalances or dysregulations can exacerbate the symptoms of fibromyalgia, making the condition more complex. While the exact mechanisms remain not fully elucidated, research has highlighted several hormones that play significant roles in the pathophysiology of fibromyalgia, including their activators and molecular targets.
Cortisol is a glucocorticoid hormone produced by the adrenal cortex, crucial in the body’s response to stress. It regulates various functions, including metabolism, immune response, and circadian rhythm. In fibromyalgia, dysregulation of cortisol secretion can contribute to increased pain sensitivity, fatigue, and mood disorders.• Activators: The hypothalamic-pituitary-adrenal (HPA) axis activates cortisol production in response to physical or emotional stress. • Molecular Targets: Cortisol acts on glucocorticoid receptors, which are widely distributed in the body, affecting numerous cellular processes including inflammatory responses and neurotransmission.
Growth Hormone (GH) is essential for growth, cell repair, and metabolism. Fibromyalgia patients often have lower levels of insulin-like growth factor 1 (IGF-1), a marker of GH activity, which could contribute to impaired tissue repair and increased sensitivity to pain. • Activators: GH secretion is regulated by growth hormone-releasing hormone (GHRH) from the hypothalamus and inhibited by somatostatin. • Molecular Targets: GH acts on growth hormone receptors on various tissues, promoting cell growth and metabolism. The liver responds to GH by producing IGF-1, which mediates many of GH’s effects.
Serotonin is not a hormone in the traditional sense, but it acts as a neurotransmitter and has hormone-like effects on mood regulation and pain perception. Low levels of serotonin are associated with increased pain sensitivity and are often observed in fibromyalgia patients. • Activators: Serotonin synthesis is activated by the essential amino acid tryptophan. • Molecular Targets: Serotonin acts on various serotonin receptors throughout the brain and body, influencing mood, pain, sleep, and gastrointestinal motility.
Norepinephrine (Noradrenaline) is both a hormone and neurotransmitter, and it is involved in the body’s stress response and regulation of blood pressure. It also affects pain pathways and mood. Dysregulation can contribute to the symptoms of fibromyalgia. • Activators: It is produced in the adrenal medulla and the locus coeruleus in the brainstem in response to stress. • Molecular Targets: Norepinephrine acts on alpha and beta-adrenergic receptors, influencing heart rate, blood pressure, and pain perception.
Estrogen and Progesterone can influence pain sensitivity and mood. Some women with fibromyalgia report symptom fluctuation with menstrual cycles, pregnancy, or menopause, suggesting a role of estrogen and progesterone in symptom modulation. • Activators: The hypothalamic-pituitary-gonadal axis regulates the production of these hormones. • Molecular Targets: Estrogen and progesterone act on their respective receptors in various tissues, affecting reproductive functions, mood, and possibly pain perception through modulation of neurotransmitter systems.
Hormonal factors in fibromyalgia indicate a complex interplay between the endocrine system and the central nervous system in regulating pain, stress response, and mood. Dysregulations in hormone levels or their signaling pathways can exacerbate fibromyalgia symptoms, highlighting the need for a comprehensive approach to treatment that may include managing hormonal imbalances. Understanding these hormonal roles and interactions remains crucial for developing targeted therapies for fibromyalgia. However, due to the multifaceted nature of fibromyalgia, treatment strategies often require a multidisciplinary approach, including pharmacological interventions, lifestyle modifications, and psychotherapy.
ROLE OF INFECTIOUS DISEASES IN FIBROMYALGIA
The relationship between infectious diseases and fibromyalgia has been a subject of interest and research for many years. While fibromyalgia is primarily characterized by widespread pain, fatigue, sleep disturbances, and cognitive issues, the onset of these symptoms has occasionally been linked to infectious illnesses. This has led to speculation and investigation into whether infections could trigger or exacerbate fibromyalgia. The theory is that certain infections may act as a precipitating factor, especially in individuals with a predisposed vulnerability, leading to the development or worsening of fibromyalgia symptoms. Here’s a closer look at how infectious diseases are thought to play a role in fibromyalgia:
The onset of fibromyalgia symptoms has sometimes been reported following viral infections. For example, illnesses such as influenza, hepatitis C, and Epstein-Barr virus (EBV) have been associated with the development of fibromyalgia-like symptoms. The exact mechanism is not fully understood, but it is believed that the immune response to the virus may lead to increased inflammation and alterations in pain perception.
Caused by the bacterium Borrelia burgdorferi, transmitted through tick bites, Lyme disease can lead to symptoms similar to those of fibromyalgia, such as fatigue, joint pain, and cognitive difficulties. Some patients diagnosed with Lyme disease continue to experience these symptoms even after the infection has been treated, a condition known as Post-Treatment Lyme Disease Syndrome (PTLDS). The relationship between Lyme disease and fibromyalgia is a topic of considerable interest and some controversy within the medical community. Lyme disease, caused by the bacterium Borrelia burgdorferi and transmitted through tick bites, can lead to a wide range of symptoms, including fatigue, joint pain, and neurological issues, which overlap significantly with those of fibromyalgia. This overlap can sometimes complicate diagnosis and management, leading to discussions on whether there is a causal relationship or simply a symptomatic similarity between the two conditions. Both conditions can present with widespread pain, fatigue, sleep disturbances, and cognitive difficulties, often leading to challenges in differential diagnosis. Some patients with Lyme disease develop Post-Treatment Lyme Disease Syndrome (PTLDS), which shares several symptoms with fibromyalgia, including persistent pain, fatigue, and cognitive fog, even after the infection has been treated. The fundamental difference lies in their causes; Lyme disease is an infectious disease caused by the Borrelia burgdorferi bacterium, whereas fibromyalgia is considered a syndrome of unknown etiology, characterized by central nervous system dysfunction leading to amplified pain perception.There is some evidence suggesting that infections, including Lyme disease, may act as a trigger for the development of fibromyalgia in susceptible individuals. The stress on the body from fighting a long-term infection could potentially lead to the dysregulation of pain pathways and immune response, contributing to fibromyalgia symptoms. The potential for false negatives in Lyme disease testing and the subjective nature of fibromyalgia diagnosis can lead to confusion. Some patients diagnosed with fibromyalgia may actually have undiagnosed Lyme disease, and vice versa. This has fueled debates on the need for more accurate diagnostic tools and criteria. For Lyme disease, early and appropriate antibiotic treatment is crucial and can prevent the development of chronic symptoms. In contrast, there is no antibiotic regimen for fibromyalgia, and treatment focuses on symptom management through a combination of medications, physical therapy, and lifestyle modifications. Given the overlapping symptoms, management of both conditions may benefit from a holistic approach that includes pain management, psychological support, and strategies to improve sleep quality and physical function. While Lyme disease and fibromyalgia share some symptomatic similarities, they are distinct conditions with different etiologies and treatment approaches. The potential for Lyme disease to trigger fibromyalgia in some individuals or for the two conditions to coexist in the same patient underscores the importance of thorough and accurate diagnosis. Continued research into the relationship between infectious diseases and syndromes like fibromyalgia is essential for developing more effective diagnostic criteria and treatment protocols, enhancing the quality of life for affected individuals.
Bacterial infections, such as those caused by Mycoplasma species, have also been suggested to trigger fibromyalgia. Research into the association between Mycoplasma infections and fibromyalgia has yielded mixed results, and more studies are needed to understand any potential link. The potential link between Mycoplasma infections and fibromyalgia has been explored in various studies, reflecting an interest in understanding the role of infectious agents in the development or exacerbation of fibromyalgia symptoms. Mycoplasma are a genus of bacteria that lack a cell wall, making them unique among prokaryotes. They can cause a variety of diseases in humans, particularly respiratory and urogenital infections. The investigation into Mycoplasma as a contributing factor to fibromyalgia stems from observations of chronic symptoms such as fatigue, muscle pain, and cognitive disturbances in patients following infections. Some research has indicated a higher prevalence of Mycoplasma infections in individuals with fibromyalgia compared to healthy controls. This has led to speculation that these infections could trigger or exacerbate fibromyalgia symptoms.The chronic infection hypothesis suggests that persistent Mycoplasma infections may lead to the development of fibromyalgia symptoms through mechanisms such as immune system activation, inflammation, and possibly autoimmunity. Mycoplasma species have been known to evade the immune system and persist in the host, potentially leading to long-term health issues. There have been studies exploring the use of antibiotics targeting Mycoplasma in patients with fibromyalgia. Some of these studies report improvements in symptoms with long-term antibiotic therapy, suggesting a potential role of Mycoplasma infections in some patients. However, these findings are controversial and not universally accepted within the medical community. The potential connection between Mycoplasma infections and fibromyalgia highlights the complex interplay between infections and chronic illness. Although intriguing, the evidence supporting a direct causal relationship is not definitive, and further research is needed. This area of study underscores the importance of a multifaceted approach to understanding and treating fibromyalgia, considering possible infectious triggers as part of a broader evaluation of the condition. It is crucial for future research to address the existing gaps in knowledge through well-designed, longitudinal studies to fully understand the impact of Mycoplasma infections on fibromyalgia.
The immune response to infections can lead to increased levels of pro-inflammatory cytokines, substances that can promote inflammation and potentially alter pain pathways. This heightened inflammatory response and its effects on the central nervous system may contribute to the onset or exacerbation of fibromyalgia symptoms.
Infections can act as physical stressors, and the stress response can exacerbate fibromyalgia symptoms. Additionally, the experience of dealing with a severe or chronic infection can be a form of psychological trauma, which is known to be a risk factor for the development of fibromyalgia.
While there is evidence suggesting a link between certain infections and the development or exacerbation of fibromyalgia, it is important to note that fibromyalgia is a multifactorial condition with a complex pathophysiology. Not everyone who experiences these infections will develop fibromyalgia, indicating that other genetic, environmental, and psychosocial factors also play significant roles. Understanding the relationship between infectious diseases and fibromyalgia could offer insights into potential treatment and prevention strategies, particularly in identifying individuals at risk and managing post-infectious symptoms more effectively. However, further research is necessary to clarify these connections and to develop targeted interventions.
CROSS REACTIVITY OF ANTIBODIES
Cross-reactivity of antibodies refers to the phenomenon where an antibody raised against a specific antigen (the target it was intended to bind to) can also bind to different, structurally similar antigens. This can occur in various diseases, including autoimmune disorders, allergies, and infections. In the context of fibromyalgia, the role of cross-reactive antibodies and their connection to the disease’s pathophysiology is an area of emerging interest, particularly regarding the theory that fibromyalgia might have an autoimmune component for some individuals.
Cross-reactivity occurs due to the structural similarities between different antigens, allowing an antibody intended to bind one antigen to mistakenly bind to another. This can happen when two antigens share a similar sequence of amino acids or a similar three-dimensional structure. In the case of autoimmune diseases, this cross-reactivity can lead to the immune system attacking the body’s own tissues, mistaking them for foreign pathogens. This results in inflammation and damage to the body’s tissues.
The exact autoantigens involved in fibromyalgia are not clearly defined, as fibromyalgia has traditionally been considered a non-inflammatory syndrome, lacking the autoantibodies typically seen in autoimmune diseases like rheumatoid arthritis or lupus. However, some research suggests that autoimmune reactions might contribute to the symptoms of fibromyalgia:
There has been speculation that antibodies may mistakenly target autoantigens in muscle tissue, potentially leading to pain and fatigue. However, specific autoantigens in fibromyalgia have not been conclusively identified. Some studies have explored the possibility that antibodies might cross-react with antigens in the nervous system, contributing to the neurological symptoms of fibromyalgia, such as pain and cognitive disturbances. For instance, research has looked into antibodies against nerve growth factor or other components of the nervous system.
There’s interest in antibodies against stress proteins (heat shock proteins), which can be upregulated in response to physical or emotional stress. These proteins, present in both pathogens and human cells, could be potential targets for cross-reactive antibodies.
Diagnosing autoimmune components in fibromyalgia is challenging due to the condition’s multifactorial nature and overlapping symptoms with other disorders. The evidence linking cross-reactive antibodies to fibromyalgia is still emerging, and much of the research is preliminary. There is ongoing debate about whether fibromyalgia should be considered an autoimmune condition. Understanding the role of autoimmunity and cross-reactive antibodies in fibromyalgia could have significant implications for treatment. If autoimmune reactions contribute to the condition, treatments targeting immune responses might be beneficial.
While the concept of cross-reactivity of antibodies provides a fascinating insight into potential mechanisms underlying fibromyalgia, conclusive evidence supporting a direct role is still lacking. Research into the autoimmune aspects of fibromyalgia, including the identification of specific autoantigens and the role of cross-reactive antibodies, is crucial. Such investigations could not only enhance our understanding of fibromyalgia’s pathophysiology but also lead to more targeted and effective treatments for those affected by this complex condition.
PSYCHOLOLOGICAL AND NEUROLOGICAL FACTORS
Fibromyalgia, a condition characterized by widespread pain, fatigue, sleep disturbances, and cognitive issues, is influenced by a complex interplay of psychological and neurological factors. The condition is thought to arise from alterations in how the central nervous system (CNS) processes pain, combined with environmental and psychological stressors. Here, we explore the role of psychological and neurological factors in fibromyalgia, with a focus on their molecular mechanisms.
Stress and trauma are significant psychological factors that can trigger or exacerbate fibromyalgia symptoms. The stress response involves the hypothalamic-pituitary-adrenal (HPA) axis, leading to increased levels of cortisol. However, in fibromyalgia, there is often dysregulation of the HPA axis, resulting in abnormal cortisol levels, which may affect pain sensitivity and mood. Stress and trauma can lead to alterations in neurotransmitter levels, including serotonin, norepinephrine, and dopamine, which play roles in mood regulation and pain perception. Chronic stress can also affect the expression of genes involved in the stress response, potentially leading to a heightened sensitivity to pain.
Anxiety and depression are common in individuals with fibromyalgia and can influence the perception of pain. These psychological conditions can exacerbate fibromyalgia symptoms through their impact on neurotransmitter systems. Conditions like anxiety and depression are associated with imbalances in neurotransmitters, such as reduced levels of serotonin and norepinephrine, which can increase pain perception. Additionally, chronic psychological stress can lead to neuroinflammation, further affecting neurotransmitter systems and pain pathways.
Central sensitization refers to an increased sensitivity to pain in the brain and spinal cord. In fibromyalgia, the CNS becomes more responsive to pain signals, amplifying them and leading to widespread pain. Central sensitization involves changes in the expression and function of neurotransmitters and their receptors in the CNS, including increased levels of substance P, glutamate, and nerve growth factor (NGF). These molecules enhance the transmission of pain signals. Additionally, alterations in ion channels and the N-methyl-D-aspartate (NMDA) receptor can increase neuronal excitability, contributing to heightened pain perception.
Sleep disturbances are a hallmark of fibromyalgia and can worsen its symptoms. Poor sleep quality can lead to increased pain sensitivity and cognitive issues. Sleep disturbances can affect the levels of neurotransmitters, such as gamma-aminobutyric acid (GABA) and melatonin, which regulate sleep-wake cycles and mood. Abnormal levels of these substances can disrupt sleep and exacerbate pain perception.
Cognitive dysfunction, often referred to as “fibro fog,” affects attention, memory, and executive function in fibromyalgia patients. Cognitive dysfunction in fibromyalgia may be linked to abnormalities in brain structure and function, particularly in regions involved in pain processing and cognitive tasks, such as the prefrontal cortex and hippocampus. Neuroimaging studies have shown altered connectivity and activity in these areas. Additionally, imbalances in neurotransmitters, such as dopamine, can affect cognitive function.
Fibromyalgia’s pathophysiology involves a complex interplay between psychological and neurological factors, each contributing to the condition’s symptomatology through specific molecular mechanisms. Stress, trauma, anxiety, and depression influence neurotransmitter levels and HPA axis function, affecting pain perception and mood. Neurologically, central sensitization, sleep disturbances, and cognitive dysfunction involve alterations in neurotransmitters, neuroinflammation, and brain connectivity. Understanding these mechanisms is crucial for developing targeted therapies that address both the physical and psychological aspects of fibromyalgia.
LIFESTYLE AND ENVIRONMENTAL FACTORS
Fibromyalgia, a chronic condition characterized by widespread pain, fatigue, and a host of other symptoms, is influenced by a complex interplay of genetic, environmental, and lifestyle factors. While the precise causes of fibromyalgia remain unclear, research suggests that lifestyle, food habits, environmental exposures, and occupational factors can impact the severity and experience of symptoms. Understanding these factors is crucial for managing fibromyalgia and improving quality of life for those affected.
Regular, moderate physical activity is shown to improve symptoms of fibromyalgia, including pain, fatigue, and sleep quality. Exercise increases the production of endorphins, the body’s natural painkillers, and can improve overall physical and mental health. A combination of aerobic exercises, strength training, and flexibility exercises, tailored to the individual’s capabilities, is often recommended.
Stress is known to exacerbate fibromyalgia symptoms. Effective stress management can reduce flare-ups and improve quality of life. Techniques such as deep breathing, meditation, yoga, and cognitive-behavioral therapy (CBT) can help manage stress.
Poor sleep can worsen symptoms of fibromyalgia. Practicing good sleep hygiene can help improve sleep quality and, by extension, reduce pain and fatigue. Establishing a regular sleep schedule, creating a comfortable sleep environment, and avoiding stimulants before bedtime are crucial steps.
While no specific diet has been proven to cure fibromyalgia, a well-balanced diet may help manage symptoms. Some individuals report that certain foods exacerbate their symptoms. Maintaining a healthy diet rich in fruits, vegetables, lean proteins, and whole grains while minimizing processed foods, sugars, and caffeine is often advised. Identifying and avoiding trigger foods through a food diary can also be beneficial.
Certain dietary supplements, such as vitamin D, magnesium, and omega-3 fatty acids, may help alleviate symptoms in some people, though evidence is mixed. Supplements should only be used under the guidance of a healthcare provider to avoid interactions with medications or other side effects.
Some evidence suggests that exposure to certain environmental pollutants and chemicals may trigger or worsen fibromyalgia symptoms, though research in this area is still evolving. Reducing exposure to pesticides, heavy metals, and air pollution where possible may be beneficial.
Jobs that involve high levels of stress or physical strain may exacerbate fibromyalgia symptoms. Work environments that do not accommodate the condition can lead to increased pain and fatigue. Seeking ergonomic adaptations, practicing stress-reducing techniques, and discussing flexible work arrangements can help manage symptoms in the workplace. Occupations that require long periods of sitting can contribute to muscle stiffness and increased pain. Incorporating regular movement and stretching into the workday can mitigate these effects.
Fibromyalgia is influenced by a wide range of factors, many of which are within an individual’s control to modify. Adopting a healthy lifestyle, managing stress, ensuring a nutritious diet, and creating a supportive work and living environment can play significant roles in managing fibromyalgia symptoms. While these strategies may not cure fibromyalgia, they can significantly improve quality of life and symptom management. It’s also essential for individuals with fibromyalgia to work closely with healthcare providers to develop a comprehensive, personalized management plan.
ROLE OF PHYTOCHEMICALS AND VITAMINS
The role of phytochemicals and vitamins in managing fibromyalgia symptoms has garnered interest due to their potential anti-inflammatory, antioxidant, and neuroprotective properties. Fibromyalgia, characterized by widespread pain, fatigue, and sleep disturbances, does not have a cure, making symptom management crucial for improving quality of life. While research is ongoing and sometimes inconclusive, certain phytochemicals and vitamins have been suggested to offer benefits for individuals with fibromyalgia.
Phytochemicals are bioactive compounds found in plants that can have health-promoting properties. Some phytochemicals of interest in fibromyalgia management include:
Flavonoids have antioxidant and anti-inflammatory effects. They may help reduce oxidative stress and inflammation, which are believed to contribute to fibromyalgia symptoms. • Sources: Fruits, vegetables, tea, wine, and chocolate.
Resveratrol is a powerful antioxidant, and may help mitigate oxidative stress and inflammation in fibromyalgia. Some research suggests it could also improve energy levels by enhancing mitochondrial function. • Sources: Grapes, berries, and peanuts.
Curcumin is known for its potent anti-inflammatory and antioxidant properties. It may help reduce pain and improve quality of life in fibromyalgia patients, although more research is needed to confirm these effects. • Sources: Turmeric.
Vitamin D deficiency has been associated with increased pain and fatigue in fibromyalgia patients. Supplementation in deficient individuals may help improve symptoms. Vitamin D can affect pain perception and muscle function, potentially benefiting those with fibromyalgia.
B vitamins, particularly B12 and folate, play roles in nerve function and energy production. While direct evidence of their benefit in fibromyalgia is limited, they may support overall health and energy levels in affected individuals. B vitamins are crucial for mitochondrial function and neurotransmitter synthesis, which could indirectly impact fibromyalgia symptoms by improving energy metabolism and reducing fatigue.
Vitamin C, an antioxidant, may help reduce oxidative stress in fibromyalgia patients. While not directly linked to symptom relief, its overall health benefits could support individuals with the condition. By reducing oxidative stress, vitamin C may help mitigate some pathways that exacerbate fibromyalgia symptoms.
Thiosinaminum, a chemical derivative of mustard seed oil, is sometimes used in alternative medicine, particularly in homeopathy, for various health issues including scar tissue, fibrosis, and certain inflammatory conditions. In the context of fibromyalgia, it is not commonly cited in mainstream medical literature as a standard treatment, but it may be considered within homeopathic practices for its purported effects on tissue health and pain management. In homeopathy, Thiosinaminum is often recommended for conditions thought to involve fibrous tissue, with the belief that it can help break down scar tissue, improve elasticity, and relieve associated pain. Thiosinaminum is thought to affect fibrous tissues, potentially helping to reduce the pain associated with fibromyalgia by influencing connective tissue and improving circulation or tissue health.
Phytolacca, commonly known as pokeweed, is a plant that has been used in traditional medicine and, more recently, in homeopathic remedies for a variety of ailments. In the context of fibromyalgia, Phytolacca is sometimes considered for its purported effects on pain and inflammation. Fibromyalgia, known for widespread pain, fatigue, and sleep disturbances, often prompts sufferers to seek a variety of treatment options, including alternative therapies. In homeopathy, Phytolacca is utilized under the principle that substances causing symptoms in a healthy person can, when highly diluted, treat similar symptoms in a sick person. Phytolacca is believed by homeopaths to be effective in treating pain and stiffness, particularly in the muscles and joints, which are hallmark symptoms of fibromyalgia. Phytolacca, contains several bioactive compounds, including a group of alkaloids that contribute to its broad range of biological activities. These alkaloids are part of the reason why phytolacca has been used in traditional medicine and also why it needs to be handled with caution due to its potential toxicity. Phytolaccine is one of the principal alkaloids found in pokeweed. It is associated with the plant’s toxic properties and can affect the central nervous system if ingested in sufficient quantities. Phytolaccatoxin is nother significant alkaloid, known for its strong emetic (causing vomiting) and purgative (laxative) properties. It also has been noted for its potential cytotoxicity, which means it can be toxic to cells. Phytolaccagenin, derived from the hydrolysis of other glycosidic compounds in the plant, this compound also contributes to the plant’s toxic profile. The plant’s alkaloids have been studied for their potential immunomodulatory and antiviral activities. The interest in pokeweed alkaloids extends into research, particularly in the investigation of their potential immunological and antiviral effects. Some studies have suggested that pokeweed antiviral protein (PAP), a protein derived from the plant, may inhibit the replication of certain viruses. However, this is distinct from the alkaloids and is a different class of compound found in the plant. There has been preliminary investigation into the use of pokeweed components in the treatment of cancer, particularly due to their potential to affect cell division and promote apoptosis (programmed cell death) in cancer cells.
The effectiveness of phytochemicals and vitamins can vary widely among individuals. Some people may experience significant benefits, while others notice minimal improvement. The source, quality, and dosage of supplements can significantly impact their effectiveness and safety. High doses of certain vitamins and supplements can have adverse effects or interact with medications. Phytochemicals and vitamins should be part of a comprehensive management plan for fibromyalgia, including physical activity, stress management, and medical therapies as recommended by a healthcare provider.
While phytochemicals and vitamins hold promise for managing fibromyalgia symptoms, more research is needed to fully understand their effectiveness and mechanisms of action. Individuals with fibromyalgia should consult healthcare professionals before starting any new supplements to ensure they are appropriate and safe based on their overall health and current treatments.
HEAVY METALS, MICROELEMENTS AND ENVIRONMENTAL POLLUTANTS
The potential link between fibromyalgia and exposure to heavy metals, microelements, and environmental pollutants is an area of growing interest and research. Fibromyalgia, characterized by widespread pain, fatigue, and cognitive disturbances, has a multifactorial etiology, with environmental factors increasingly recognized as possible contributors to the development and exacerbation of symptoms. Understanding the role of these environmental factors is crucial for developing more comprehensive management strategies for individuals with fibromyalgia.
Exposure to heavy metals such as lead, mercury, cadmium, and arsenic.
has been associated with various health issues, including neurological and immune system dysfunction, which can potentially exacerbate fibromyalgia symptoms. For instance, mercury can disrupt neurotransmitter pathways and lead may affect nerve function, both of which could potentially influence pain perception and cognitive function in fibromyalgia. Heavy metals may contribute to oxidative stress and inflammation, leading to cellular damage and affecting the central nervous system’s pain processing pathways. They can also disrupt endocrine function, potentially impacting stress response mechanisms and hormonal balance, which are already dysregulated in many fibromyalgia patients.
Adequate levels of these microelements microelements such as Iron, zinc, magnesium, and selenium are essential for various bodily functions, including immune response and enzyme activity. Imbalances (both deficiencies and excesses) can influence fibromyalgia symptoms. For example, magnesium is crucial for muscle and nerve function, and deficiencies have been linked to increased pain and fatigue. Microelements play roles in mitochondrial energy production, neurotransmitter synthesis, and antioxidative defense mechanisms. Deficiencies or imbalances can lead to decreased energy production, altered neurotransmitter activity, and increased oxidative stress, potentially exacerbating fibromyalgia symptoms.
Environmental Pollutants such as pesticides, bisphenol A (BPA), polychlorinated biphenyls (PCBs), and particulate matter can affect the immune and endocrine systems, contributing to the chronic pain and fatigue characteristic of fibromyalgia. For instance, pesticides and PCBs have been shown to disrupt hormonal activity and could potentially influence the severity of fibromyalgia symptoms through endocrine disruption. Many environmental pollutants act as endocrine disruptors or contribute to oxidative stress and inflammation. These mechanisms can potentially influence pain pathways, immune responses, and hormonal balance, all of which are relevant to the symptomatology of fibromyalgia.
While the direct links between heavy metals, microelements, environmental pollutants, and fibromyalgia are still under investigation, the potential for these factors to contribute to symptom severity warrants attention. The mechanisms through which these environmental factors impact fibromyalgia may include oxidative stress, inflammation, endocrine disruption, and direct effects on the central nervous system. Reducing exposure to harmful substances, ensuring adequate intake of essential microelements through diet or supplementation, and addressing individual sensitivities may be beneficial as part of a comprehensive approach to managing fibromyalgia. However, more research is needed to fully understand these relationships and to develop targeted interventions aimed at reducing the impact of environmental factors on fibromyalgia symptoms.
Hyperalgesia is a condition characterized by an increased sensitivity to pain, where a person experiences an exaggerated pain response to stimuli that are normally painful. This heightened sensitivity can result from changes within the central or peripheral nervous systems, leading to an amplified perception of pain. Hyperalgesia is an important concept in understanding various pain syndromes and is particularly relevant in chronic pain conditions, opioid-induced sensitivity, and certain neurological disorders. Diseases or injuries affecting nerves can lead to central sensitization, resulting in secondary hyperalgesia. Long-term use of opioids can paradoxically increase the body’s sensitivity to pain, a phenomenon known as opioid-induced hyperalgesia (OIH). This is thought to result from neuroplastic changes in the central nervous system caused by prolonged opioid exposure. Fibromyalgia is a chronic pain syndrome is believed to involve central sensitization, making patients more susceptible to hyperalgesia.
MODERN CHEMICAL DRUGS
The relationship between modern chemical drugs and the causation of fibromyalgia is complex and multifaceted. While there is no direct evidence to suggest that chemical drugs cause fibromyalgia, certain medications can potentially contribute to the onset or exacerbation of symptoms associated with this condition. Here are several perspectives on how modern chemical drugs might relate to fibromyalgia:
Some medications can induce side effects that mimic or exacerbate fibromyalgia symptoms. For example, drugs that affect the central nervous system (CNS), such as certain types of antidepressants, anticonvulsants, or sedatives, might contribute to fatigue, cognitive disturbances (“fibro fog”), or even muscle pain in sensitive individuals. However, it’s important to distinguis32h between temporary side effects of medication and the chronic, pervasive symptoms characteristic of fibromyalgia.
Certain drugs can increase sensitivity to pain, a hallmark of fibromyalgia. Medications that interfere with neurotransmitter levels, such as serotonin and norepinephrine, might affect pain perception pathways. Over time, this can potentially alter pain processing in the CNS, leading to increased pain sensitivity similar to that observed in fibromyalgia.
Overuse of certain medications, particularly opioids and some nonsteroidal anti-inflammatory drugs (NSAIDs), can lead to increased pain sensitivity, known as hyperalgesia. This phenomenon bears similarity to the central sensitization seen in fibromyalgia, where the CNS becomes more responsive to pain signals, amplifying them.
Drugs that affect hormone levels, such as corticosteroids or some hormonal therapies, can impact the hypothalamic-pituitary-adrenal (HPA) axis, an integral part of the body’s stress response system. Dysregulation of the HPA axis has been implicated in fibromyalgia, suggesting that drugs influencing this system could potentially contribute to the development or worsening of symptoms.
The discontinuation of certain medications, especially those used for pain management or psychiatric conditions, can lead to withdrawal symptoms that may temporarily mimic fibromyalgia, such as widespread pain, sleep disturbances, and mood changes. While these symptoms are usually transient, they can be distressing and may complicate the clinical picture.
Although there is no conclusive evidence that modern chemical drugs directly cause fibromyalgia, certain medications can contribute to symptom onset or exacerbation in susceptible individuals. It’s crucial for patients and healthcare providers to closely monitor the effects of medications, especially when starting new treatments or adjusting dosages. The potential impact of drugs on fibromyalgia symptoms underscores the importance of a careful, personalized approach to medication management in individuals with or at risk of developing fibromyalgia. Further research is needed to explore the complex interactions between medication use and fibromyalgia symptoms, as well as to identify strategies for minimizing adverse effects while effectively managing the condition.
MIT HOMEOPATHY APPROACH TO THERAPEUTICS OF FIBROMYALGIA
DRUG MOLECULES act as therapeutic agents due to their CHEMICAL properties. It is an allopathic action, same way as any allopathic or ayurvedic drug works. They can interact with biological molecules and produce short term or longterm harmful effects, exactly similar to allopathic drugs. Please keep this point in mind when you have a temptation to use mother tinctures, low potencies or biochemical salts which are MOLECULAR drugs.
On the other hand, MOLECULAR IMPRINTS contained in homeopathic drugs potentized above 12 or avogadro limit act as therapeutic agents by working as artificial ligand binds for pathogenic molecules due to their conformational properties by a biological mechanism that is truly homeopathic.
Understanding the fundamental difference between molecular imprinted drugs regarding their biological mechanism of actions, is very important.
MIT or Molecular Imprints Therapeutics refers to a scientific hypothesis that proposes a rational model for biological mechanism of homeopathic therapeutics. According to MIT hypothesis, potentization involves a process of ‘molecular imprinting’, where in the conformational details of individual drug molecules are ‘imprinted or engraved as hydrogen- bonded three-dimensional nano-cavities into a supra-molecular matrix of water and ethyl alcohol, through a process of molecular level ‘host-guest’ interactions. These ‘molecular imprints’ are the active principles of post-avogadro dilutions used as homeopathic drugs. Due to ‘conformational affinity’, molecular imprints can act as ‘artificial key holes or ligand binds’ for the specific drug molecules used for imprinting, and for all pathogenic molecules having functional groups ‘similar’ to those drug molecules. When used as therapeutic agents, molecular imprints selectively bind to the pathogenic molecules having conformational affinity and deactivate them, thereby relieving the biological molecules from the inhibitions or blocks caused by pathogenic molecules.
According to MIT hypothesis, this is the biological mechanism of high dilution therapeutics involved in homeopathic cure. According to MIT hypothesis, ‘Similia Similibus Curentur’ means, diseases expressed through a particular group of symptoms could be cured by ‘molecular imprints’ forms of drug substances, which in ‘molecular’ or crude forms could produce ‘similar’ groups of symptoms in healthy individuals. ‘Similarity’ of drug symptoms and diseases indicates ‘similarity’ of pathological molecular inhibitions caused by drug molecules and pathogenic molecules, which in turn indicates conformational ‘similarity’ of functional groups of drug molecules and pathogenic molecules. Since molecular imprints of ‘similar’ molecules can bind to ‘similar ligand molecules by conformational affinity, they can act as the therapeutics agents when applied as indicated by ‘similarity of symptoms. Nobody in the whole history could so far propose a hypothesis about homeopathy as scientific, rational and perfect as MIT explaining the molecular process involved in potentization, and the biological mechanism involved in ‘similia similibus- curentur, in a way fitting well to modern scientific knowledge system.
If symptoms expressed in a particular disease condition as well as symptoms produced in a healthy individual by a particular drug substance were similar, it means the disease-causing molecules and the drug molecules could bind to same biological targets and produce similar molecular errors, which in turn means both of them have similar functional groups or molecular conformations. This phenomenon of competitive relationship between similar chemical molecules in binding to similar biological targets scientifically explains the fundamental homeopathic principle Similia Similibus Curentur.
Practically, MIT or Molecular Imprints Therapeutics is all about identifying the specific target-ligand ‘key-lock’ mechanism involved in the molecular pathology of the particular disease, procuring the samples of concerned ligand molecules or molecules that can mimic as the ligands by conformational similarity, preparing their molecular imprints through a process of homeopathic potentization upto 30c potency, and using that preparation as therapeutic agent.
Since individual molecular imprints contained in drugs potentized above avogadro limit cannot interact each other or interfere in the normal interactions between biological molecules and their natural ligands, and since they can act only as artificial binding sites for specific pathogenic molecules having conformational affinity, there cannot by any adverse effects or reduction in medicinal effects even if we mix two or more potentized drugs together, or prescribe them simultaneously- they will work.
Based on the detailed analysis of pathophysiology, enzyme kinetics and hormonal interactions involved, MIT approach suggests following molecular imprinted drugs to be included in the therapeutics of FIBROMYALGIA:
Serotonin 30, Dopamine 30, Adrenalin 30, Cortisol 30, Glutamic acid 30, Arachidonic acid 30, Calcium carbonate 30, Somatostatin 30, Diethylstilbesterol 30, Influenzinum 30, Epstein-Barr virus 30, Lyme disease nosode 30, Mycoplama 30, Melatonin 30, Arsenic Album 30, Cadmium 30, Plumbum met 30, Thiosinaminum 30, Phytolacca 30
REFERENCES:
- Wolfe F, Smythe HA, Yunus MB, et al. The American College of Rheumatology 1990 Criteria for the Classification of Fibromyalgia. Report of the Multicenter Criteria Committee. Arthritis & Rheumatism. 1990;33(2):160-172. DOI: 10.1002/art.1780330203.
- Clauw DJ. Fibromyalgia: A Clinical Review. JAMA. 2014;311(15):1547-1555. DOI: 10.1001/jama.2014.3266.
- Staud R. Brain Imaging in Fibromyalgia Syndrome. Clinical and Experimental Rheumatology. 2011;29(6 Suppl 69):S109-17. PMID: 22243559.
- Littlejohn G, Guymer E. Neurogenic inflammation in fibromyalgia. Seminars in Immunopathology. 2018;40(3):291-300. DOI: 10.1007/s00281-018-0672-2.
- Häuser W, Walitt B, Fitzcharles MA, Sommer C. Review of pharmacological therapies in fibromyalgia syndrome. Arthritis Research & Therapy. 2014;16(1):201. DOI: 10.1186/ar4441.
- Bidonde J, Busch AJ, Schachter CL, et al. Aerobic exercise training for adults with fibromyalgia. Cochrane Database of Systematic Reviews. 2017;6:CD012700. DOI: 10.1002/14651858.CD012700.
- Jones KD, Gelbart T. Managing Fibromyalgia Syndrome Among Young and Middle-Aged Adults With Complementary and Alternative Medicine. CAM Journal. 2019;15(3):e14525. DOI: 10.5812/cam.14525.
- Kim YS, Lee J, Park W. Effect of Vitamin D Supplementation in Patients with Fibromyalgia: A Systematic Review and Meta-analysis. Rheumatology International. 2021;41(2):315-327. DOI: 10.1007/s00296-020-04719-0.
- Arnold LM, Clauw DJ, McCarberg BH. Improving the recognition and diagnosis of fibromyalgia. Mayo Clinic Proceedings. 2011;86(5):457-464. DOI: 10.4065/mcp.2010.0738.
- Thieme K, Turk DC, Flor H. Comorbid depression and anxiety in fibromyalgia syndrome: Relationship to somatic and psychosocial variables. Psychosomatic Medicine. 2004;66(6):837-844. DOI: 10.1097/01.psy.0000146329.63158.40.
- Macfarlane GJ, Kronisch C, Dean LE, et al. EULAR revised recommendations for the management of fibromyalgia. Annals of the Rheumatic Diseases. 2017;76(2):318-328. DOI: 10.1136/annrheumdis-2016-209724.
- Fitzcharles MA, Ste-Marie PA, Goldenberg DL, et al. 2012 Canadian Guidelines for the diagnosis and management of fibromyalgia syndrome: Executive summary. Pain Research & Management. 2013;18(3):119-126. DOI: 10.1155/2013/918216.
- www.redefininghomeopathy.com. Chandran Nambiar K C
- JH Clarke. Dictionary of Homeopathy Materia Medica
REDEFINING HOMEOPATHY 