FIBROMYALGIA AND THE NEUROBIOLOGY OF CHRONIC PAIN

“Bad things do happen; how I respond to them defines my character and the quality of my life. I can choose to sit in perpetual sadness, immobilized by the gravity of my loss, or I can choose to rise from the pain and treasure the most precious gift I have - life itself.”

- Walter Anderson

Chronic pain is one of the most challenging health conditions to-date, and sadly, one of the least understood. The following article highlights what is known about both chronic pain and fibromyalgia. Symptoms, potential causes, risk factors and treatment options are discussed below.

What is Fibromyalgia?

Fibromyalgia is a condition in which the body’s ability to process and perceive pain becomes dysfunctional^[1]. Patients with Fibromyalgia often feel pain from stimuli that are simply not painful. Pain can be triggered by emotional, mental or physical stimuli, such as stress, traumatic ideation or physical touch. The disease shares commonality with small nerve fiber neuropathies in which sensations of light touch induce a heightened feeling of pain, such as being in contact with a bed sheet.

Other conditions that share some overlap with clinical features of fibromyalgia include insulin resistance, chronic fatigue syndrome, major depressive disorder and other mood disorders. Onset noticeably occurs after a traumatic event in a large number of cases, implicating severe stress as a major trigger. Other cases of fibromyalgia have manifested in the absence of a known trigger, slowly developing over time.

Symptoms of Fibromyalgia

Common symptoms of fibromyalgia include^[2]:

• Inappropriate Pain Response. Those with fibromyalgia tend to experience pain in response to both painful and non-painful stimuli.
• Widespread “Global” Pain. This refers to pain in all or most bodily areas. The pain is experienced on both sides of the body, as well as on the top and bottom halves. It is often a dull low-grade pain that does not go away for a period of at least 3 months.
• Chronic Fatigue. Many with fibromyalgia experience chronic fatigue syndrome, wherein they are physically exhausted most of the time. Some with chronic fatigue can’t stop sleeping during the day, however, sleep disruption and/or poor sleep quality is common.
• Sleep Disruption. A poor quality of sleep and sleep disturbance is common to those who experience chronic pain. Those who battle to sleep at all with the condition may experience worse symptoms.
• Mood Swings. Depression and anxiety are common to those with fibromyalgia, as are mood swings coupled with erratic energy levels. Typically these fluctuations are not as drastic as seen in manic depression. Some patients may experience extreme psychological distress.
• Fibro Fog. Chronic pain makes it difficult for those with the condition to focus and think clearly, often referred to as “fibro fog.” Often, memory and learning ability are significantly reduced.

Those with fibromyalgia may also present with obesity, tension headaches or migraines, poor posture, temporomandibular joint disorders, weaker immune function, chronic infections and digestive ailments. Other conditions associated with fibromyalgia include restless leg syndrome, PTSD, mast cell activation syndrome, myalgic encephalomyelitis and myofascial pain syndrome.

Potential Causes: Neurobiology of Pain & Augmented Pain Processing in Fibromyalgia

The vast majority of those with fibromyalgia develop the condition as a result of prolonged regional pain, which may be induced physically or chemically.

Pain perception is a very complex process that consists of multiple variables. In Fibromyalgia, it is uncertain where along the line pain perception becomes heightened and confused with other sensory stimuli, with distortions in multiple areas of the nervous system having been observed across all members with the illness:

1. Peripheral Nervous System Sensing

As many as two-thirds of patients with fibromyalgia display small fiber nerve damage, and a lesser amount of small nerve fibers compared to healthy individuals. In this situation, the small nerves connected to skin and vital organs in the periphery are not functioning optimally^[3]. It is suggested that a reduced number of functional small nerve fibers is connected to a heightened sensation of pain and less resilience toward painful stimuli. Small nerve fiber neuropathy is believed to be connected to a form of insulin resistance^[4], however not all patients with fibromyalgia present with neuropathy.

2. Spinal Column: Ascending And Descending Pain Pathways

The nerves of the periphery connect with nerve clusters in the spinal column that protrude into the brain. In some cases of fibromyalgia, the signals in the spinal column are faulty, promoting non-stop signals of pain to be transmitted either to the brain or from the brain to the periphery.

3. Central Nervous System Processing

Within the brain, pain processing itself is highly complex and involves many areas across all cortices. In those with fibromyalgia, brain scans reveal that activity in any of these regions is typically amplified at central hubs where processing points intersect^{[5] [6]}. In some cases, any signals traversing these areas can serve as a trigger as the signals become amplified and end up triggering the networks involved in pain processing. As these hubs are not only involved in pain processing, the trigger can seem almost random or highly specific to each individual with the disease.

It has been noted that the insula is a common triggering hub in the brains of those with fibromyalgia^[7], often part of the network involved in pain amplification. As the insula is involved in processing personality, consciousness, trauma, emotion and memory, a wide array of stimuli can trigger pain in a person with fibromyalgia. This coincides with psychological theories that note that those with the condition have “weak personalities” and are more susceptible to any kind of mental-emotional stressor.

4. Neurotransmitters Involved in Pain

Alterations in neurotransmitter levels are noted in those with both chronic fatigue syndrome and fibromyalgia, for which there is a significant overlap in neurological profiles. In response to chronic pain signaling, both serotonin and dopamine can become depleted and act erratically^[8]. As serotonin is required to produce and activate dopamine, and dopamine is the precursor to norepinephrine which drives our basic level of waking arousal throughout the day, a lack of these neurotransmitters results in severe fatigue.

Furthermore, in subsets of patients with fibromyalgia, excitatory neurotransmitters such as glutamate are increased while inhibitory neurotransmitters such as GABA are decreased.

5. Mast Cell Activation

Mast cells are involved in the immune reactions underlying the pain and inflammation associated with tissue damage, open wounds and allergies. Upon activation, they release compounds that sensitize neurons to pain, triggering an inflammatory pain response. They are also capable of alerting immune cells of painful stimuli, which then serve to activate pain-related pathways in the nervous system.^[9]

6. Opioid System Dysfunction

Opioids are compounds found throughout nature in the form of sugars, with cane sugar perhaps being the most famous type consumed on mass. The body happens to also make its own opioids, which serve as vital signaling molecules within the endocrine and nervous systems. Endogenous opioids and their receptors make up the opioid system^{[10] [11]}. These compounds are involved in a number of bodily functions, with the best studied functions being related to pain perception and the body’s natural ability to block pain.

In those with fibromyalgia, natural opioid production and receptor expression is dysfunctional, resulting in increased sensitivity to pain. Research reveals that patients typically have an increased level of opioids in neuronal synapses, however, the opioids fail to make it to the appropriate receptors. Other studies reveal a decrease in available opioid receptors.^[12]

Fibromyalgia Risk Factors

Risk factors for fibromyalgia include:

• Chronic or severe stress. Stress is a known trigger for both insulin resistance and adrenal “burnout”, both of which contribute directly to many of the underlying mechanisms noted to be at play in fibromyalgia. The large majority of those with this condition endured some type of extreme trauma^[13] in their lives, especially in childhood^[14], that precipitated disease onset.
• Insulin Resistance. Insulin is required for optimal metabolic signaling in all cells, including in muscle and nerve fiber cells. Insulin resistance, where the cells are unable to take up insulin, results in muscle stiffness, increased musculoskeletal pain, erratic energy levels and eventually nerve fiber atrophy. Many with fibromyalgia are noted to have some degree of insulin resistance.^[15]
• Chronic Infection. Chronic infections increase the risk of getting fibromyalgia through numerous actions^[16]. Many chronic infections promote hyperglycemia and eventual insulin resistance, deplete serotonin, and may add to painful sensations in the body in the form of muscle stiffness, cramps, etc. Furthermore, some infections have evolved in such a way that actively interferes with hormonal signaling in the body. Neurological infections are capable of inducing nerve damage and promoting abhorrent nerve signaling that can also exacerbate the risk for acquiring fibromyalgia.
• Autoimmunity. Autoimmune diseases, particularly neurological and systemic types, can increase the risk of fibromyalgia^[17] by contributing towards small nerve fiber neuropathy, impaired immune functioning and insulin resistance. Furthermore, autoimmune conditions are characterized by the immune system attacking the body’s own tissues, which can trigger pain signaling through mast cell activation.
• Genetics. Fibromyalgia is noted to run in families and there are a few inheritable genes suspected of increasing the risk. These are related to autoimmunity and stress resilience.
• Female Gender. In general, more women acquire fibromyalgia than men. This could be related to a number of reasons, some of which are genetic (i.e. women are at an increased risk for autoimmunity) and others of which pertain to socio-economic factors. Women are often subject to a lot more stress on average, particularly in settings of domestic violence.
• Moderate to Severe Allergy. As allergy is known to trigger mast cells and produce pain-related compounds, chronic exposure to allergens may exacerbate symptoms of fibromyalgia. Those with fibromyalgia were frequently found to be hyper-allergenic.^{[18] [19]}
• Smoking. While it is unknown whether smoking is a risk factor for fibromyalgia onset, it has been linked with worsening symptoms of pain and fibro fog.^[20]
• Obesity. Many patients with fibromyalgia are obese and obesity appears to increase the severity of fibromyalgia.^[21] Various cellular changes that co-arise with obesity serve as additional risk factors for fibromyalgia, including insulin resistance, depression, fatigue, and opioid system dysfunction.^[22]
• Arthritis. Anyone with a form of arthritis or rheumatic disease^[23] is at an increased risk for developing fibromyalgia, due to being subject to chronic pain.^[24] Arthritis is a component of many types of disease, including chronic infections, thyroid conditions, bone disease and autoimmune conditions.

Treatment Options for Fibromyalgia

Fibromyalgia is often treated with the help of a qualified rheumatologist. Due to its prevalence amongst those with other systemic diseases that produce pain, it can be difficult to diagnose. Those with fibromyalgia may not experience all the common symptoms; however, the symptoms they do have will be out of proportion in the context of other ailments.

1. Pharmaceutical Interventions

Many patients with fibromyalgia are highly sensitive towards any kind of pharmaceutical medication. As a result, the condition is generally managed by improving lifestyle parameters. A skilled rheumatologist understands this and will prescribe drugs with caution, starting at the lowest dose possible and gently working towards an acceptable level in order to alleviate symptoms.^[25]

• Antidepressants

Some patients with fibromyalgia respond to antidepressants that increase the reuptake of serotonin and noradrenaline. In a subset of patients, this tends to improve on symptoms of depression, anxiety, concentration and fatigue. However, the majority of those with fibromyalgia typically do not respond to antidepressants as they do not treat the main presenting symptoms. When considering antidepressant treatment, it should be noted that depression, anxiety and fatigue are secondary symptoms that are the result of chronic widespread pain.

• Anti-epileptics

Anti-epileptic drugs are an experimental approach for treating fibromyalgia that have begun to gain traction over the years. These medications block the action of excitatory neurotransmitters such as glutamate by providing synthetic forms of inhibitory neurotransmitters (e.g. pregabalin). These may be effective for cases of fibromyalgia that have central nervous system involvement. Anti-epileptics may improve the quality of sleep and reduce pain intensity in this subset of patients.

2. Psychotherapy

Living with fibromyalgia is often exceedingly difficult, particularly due to the stressful nature of the condition. Those with the diseases typically fluctuate between depression and severe anxiety, both of which worsen the symptoms of the disease and can be exacerbated by the way in which one thinks. To make matters worse, it was not until recent years that fibromyalgia was accepted as a medical condition.

A skilled psychotherapist is able to reassure the patient that the condition is real, as well as help them to shift their mindset and work towards a more positive mental approach. This in turn can help to ease the psychological component of the disease, which typically resembles (and can also be related to) a form of trauma.

3. Routine Physical Exercise

Physical exercise is strongly advised for those with fibromyalgia, as the effects on the nervous system help to alleviate many of the chemically-induced symptoms. Exercise increases the levels of neurotransmitters lacking in those with fibromyalgia and chronic fatigue syndrome, such as serotonin and dopamine. It also promotes the release of endorphins and other pain-relieving compounds that serve to stabilize the body’s opioid system.

In spite of the benefits, exercise should be tempered according to the person’s fitness level to avoid exhaustion and excessive muscle breakdown. Those with fibromyalgia would benefit from wearable fitness trackers that can help them to be consistent with exercise, as well as to frequently improve the amount of exercise done on a daily basis until a sufficient threshold is reached. These patients can benefit from more exercise than the average healthy individual, provided they work towards increasing their fitness levels slowly without causing more stress on their bodies.

At the very least, 30mins of aerobic exercise 3 times a week is required. Yoga, water-based exercise and other therapeutic forms of exercise may also be beneficial.

4. Sleep Hygiene

Those with fibromyalgia often have a type of sleep disorder which serves to create a catch 22, wherein poor sleep quality increases pain and pain increases poor sleep quality^[26]. It is absolutely essential that those with fibromyalgia make an active effort to practice good sleep hygiene.

Good sleep hygiene is characterized by:

• Getting to sleep at a reasonable time.
• Winding down activity 1-2 hours before bedtime, including electronic activity and exposure to bright artificial light.
• Avoiding food and beverages in the hour before sleep.
• Sleeping for at least 8 hours a night and resting for that time if sleep is difficult to achieve.

Naps throughout the day may help to combat fatigue; however, extended periods of daytime sleep should be avoided in order to promote good sleep hygiene.

Conclusion

Fibromyalgia and chronic widespread pain are conditions that are common developments present amongst many patients with painful disorders. Little is known about the underlying causes, however, in every case, faulty pain processing is the main theme. Poor lifestyle choices, physically traumatic experiences, chronic disease, under-functioning metabolism and female gender appear to be prime risk factors. While painkillers may seem to be an obvious treatment option, they are often ineffective. Low doses of antidepressants, anti-epileptics and weak opioids may be beneficial in managing symptoms. Regular exercise, consuming a healthy diet, therapy and practicing good sleep hygiene are key to managing symptoms of fibromyalgia.

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