Research Projects Funded

AFSA is the only charitable organization whose primary mission is to seed research on fibromyalgia. We acknowledge that patient and physician education, public awareness and advocacy are all important ingredients in aiding the lives of people with fibromyalgia. However, advances in research provide the most crucial ingredient for enriching the daily well-being of those who suffer with this hard-to-treat disease. Our research-funding objective is to advance the science of fibromyalgia, as well as provide better therapeutic interventions for all patients.

Brain-Immune Interactions in Fibro Flares
(September 2024 – Approved, pending IRB)

The brain, spinal cord and the immune system are all involved in generating the symptoms of fibromyalgia. Determining which system drives the others to malfunction is unclear and is the focus of this study. Nick Fallon, Ph.D., and Andreas Goebel, M.D., Ph.D., will assess how these systems interact during baseline conditions and during serious symptom flares. Comparing the physiological processes occurring in patients at the two points of time will help clarify the dynamics of the disease.

Gut Bacteria’s Influence on Cannabis Trial
(July 2024)

Gut microbes, called your microbiota, are substantial altered in people with fibromyalgia and contribute to the symptoms. Several studies indicate one-fourth of fibromyalgia patients may benefit from cannabis, but the response is variable. This difference in response among patients is thought to be tied to the microbiota. Amir Minerbi, M.D., Ph.D., of Israel, is conducting a large, placebo-controlled trial of medical grade cannabis oil in 150 patients. Not only will he assess symptoms and side effects, he is also examining the role the microbiota plays in treatment success.

CES for Treating Fibro
(June 2024)

Cranial electrical stimulation (CES) is nondrug therapy that is suspected to favorably improve the way the brain functions. Several studies indicate it treats many symptoms associated with fibromyalgia. However, it hasn’t been thoroughly investigated for the treatment of this disease. Anna Woodbury, M.D., M.Sc., of Emory University in Atlanta is evaluating the ability of CES to reduce fibromyalgia symptoms and produce favorable changes in brain function.

Brain Response to Immune Challenge
(January 2020)

Infections make fibromyalgia symptoms worse … long after the bacteria or virus is gone. One possible reason for why this happens involves the immune cells in the brain, called microglia. When they sense a threat to the brain (such as an infection), they go on a war-like rampage to neutralize it. In the process, they produce many chemicals and metabolic waste products that are associated with common fibromyalgia symptoms.

“We believe the microglia are hypersensitized in fibromyalgia,” says Jarred Younger, Ph.D., the principal investigator of this project. In other words, subtle immune insults or minor nuisance threats are causing a robust activation of the microglia. And this could explain why living with fibromyalgia is a bumpy road full of symptom ups and downs.

This study looks at the metabolic processes in the brains of fibromyalgia patients before and after a mild immune challenge. Based on the results, the microglia are behaving abnormally in fibromyalgia patients. In addition, these cells are burning through the brain’s energy supply and ramping up the temperature in the brain.

Detecting Brain Inflammation using PET
(February 2019)

Feel like you have a nasty flu bug that never leaves? This study provides a scientific reason for this! Immune cells (called microglia) in the brain go ballistic in an effort to protect your brain when a virus enters your system. After all, it would be bad news if the virus gained access to your brain. But in the process of protecting the brain, these immune cells secrete chemicals that make people sick … at least for a day or two. Based on the results of this study (published in PAIN, October 2023), these cells are chronically “turned on” to cause inflammation throughout the brain and are linked to greater pain, fatigue, and fibrofog.

DRG, Sodium Channels, and Fibromyalgia Sympathetic Pain
Principal Investigator: Manuel Martiniz-Lavin, M.D. (Mexico)
(September 2010)

The dorsal root ganglia (DRG) house the cell bodies of sensory neurons and are located up and down each side of the spinal cord. The DRGs can modulate signals before entering the spinal cord and one mechanism is via sodium channels. A genetic variant of the sodium channels, called SCN9A, can lead to an enhanced signal leaving the DRGs. Martinez-Lavin looked to see if this genetic variant was more common in fibromyalgia patients and here is what he found:

patients exhibited a higher prevalence of the SCN9A sodium channel gene variant and it tended to occur in a subgroup of patients with very severe symptoms
this study provides preliminary evidence for the use of sodium channel blockers for treating fibromyalgia, such as lidocaine … and more specific medications with less side effects are being developed

The results were published in BMC Musculoskeletal Disorders (2012).

The above findings help explain a 1997 report in Journal of Rheumatology. Researchers showed that 18 fibromyalgia patients responded differently to intravenous doses of lidocaine, ketamine, and morphine. Three patients did not respond to any of the treatments, but 30-60 percent of the remaining patients responded extremely well to one or more of the medications. Different genetics and physiological mechanisms are contributing to the symptoms of fibromyalgia.

Fibromyalgia patients responding to lidocaine may have the SCN9A gene variant or a sodium channel problem related to the functioning of their DRGs. Patients responding to ketamine may have more activated NMDA receptors in their spinal cord that amplifies their pain. Alternatively, they may have a severe reduction of dopamine in their nervous system because ketamine also raises dopamine. Patients responding to morphine may have a greatly impaired pain inhibitory system (or what researchers call a system that facilitates pain instead of relieving it). FYI – Dextromethorphan may be a suitable substitute for ketamine …see 1997 trial below.

Genetic Influences on the Pain Control System
(October 2009)

“There is a genetic predisposition to developing fibromyalgia, so why not look at the main neurotransmitters that play a role in pain control?” asks Serge Marchand, Ph.D., the principal investigator. The body’s pain inhibitory controls in the central nervous system rely heavily on serotonin and dopamine. When a potentially painful stimulus enters the spinal cord, one of these transmitters signal the release of opioid-like pain relievers. Genetic glitches that alter the function of dopamine and serotonin could help explain why people with fibromyalgia have so much pain.

Biomarker Expression on Blood Leukocytes
(September 2009)

Could your body be making too many sensory receptors that are actively sounding off the alarms for pain and fatigue? If so, your brain would be bombarded with these signals while resting, and perhaps even more so during exercise. Identifying biomarkers on leukocytes (white blood cells) in people with fibromyalgia was the goal of this study, and it turned up several exciting new findings.

Low-Dose Naltrexone (LDN) for Treating Fibro
(September 2008)

Most treatments for fibromyalgia are designed to improve the operation of the pain control mechanisms in the central nervous system (CNS). In other words, they target the neurons. But you have immune cells in your CNS that exert a tremendous influence over how your neurons work to control pain. More than one study has now shown that these immune cells are on the rampage in fibromyalgia and they need to be quieted down. LDN is different from most drugs that treat fibromyalgia because it does not target the neurons, it works to quiet down these immune cells. The goal of this treatment trial is to determine if LDN can reduce the symptoms of fibromyalgia.

Role of Myofascial Trigger Points (MTPs)
(September 2008)

You’ve probably felt the rock-like nodules or knots in your muscles called myofascial trigger points or MTPs. When pressed, MTPs hurt and radiate pain. Yet, no studies have been done to determine how many MTPs fibromyalgia patients have, where they are most often located, and how they may be contributing to the symptoms. MTPs give off spontaneous electrical activity and can be objectively identified by electromyography. Hong-You Ge, M.D., Ph.D., of Denmark, will use electromyography to evaluate fibromyalgia patients for MTPs and determine the role they play in producing fibromyalgia pain. Ge found that MTPs play a substantial role in generating your symptoms, which means more focus should be placed on treating them.

The Impact of MTPs on Pressure Pain Thresholds
(September 2008)

Cesar Fernandez de las Penas, Ph.D., of Spain, will take a different approach to the project listed above by Dr. Hong-You Ge. Both studies will determine the prevalence of MTPs, but this project will assess the impact of MTPs on each fibromyalgia patient’s pressure pain threshold. The lower the pain threshold, the less effective the central nervous system’s pain control mechanisms are. In addition, the 18 tender point areas that were used for decades to diagnose fibromyalgia were evaluated for the presence of MTPs. This goal will also be assessed by the above study. Why the overlap? It will take more than one research team to prove that most of the tender points (90 percent) are MTPs, which are treatable problems in the muscles.

Establishing a Fibromyalgia Tissue Donation Program
Principal Investigators: Linda Watkins, Ph.D., and Dianne Lorton, Ph.D. (USA)
(2006)

This project is an expansion of the 2004 award to Watkins and Lorton for evaluating central nervous system (CNS) tissue from fibromyalgia patients and healthy controls. After additional staff were recruited (especially a rheumatologist to oversee fibromyalgia patient recruitment), Lorton successfully received a huge 5-year grant from NIH to continue the project. By 2011, more than 170 fibromyalgia patients and matched controls were enrolled in the study. The program was self-sufficient with funding from a pharmaceutical companies and other funding entities interested in studying fibromyalgia. Unfortunately, Banner Health bought SHRI near the end of 2011. They cancelled the project and fired all the staff that had been put in place to run the program.

This was an ambitious project that never would have gotten off the ground, had it not been for AFSA’s generous donors (the NIH required proof of concept). It was the only tissue donation program of its kind in the world, and it included fibromyalgia! Within 20 years after its inception, fibromyalgia researchers would certainly have access to human tissue (especially the brain and spinal cord). Progress on fibromyalgia would be zooming ahead if it were not for Banner’s corporate greed. Not only were fibromyalgia patients willing to donate the funds to get this amazing project off the ground, but they were also willing to sign up to be the tissue donors.

COMT Gene Contribution to Pain in Fibromyalgia Principal Investigator: Manuel Martinez-Lavin, M.D. (Mexico) (2006)

COMT is an enzyme that degrades norepinephrine. This neurotransmitter can rev up the sympathetic branch of the autonomic nervous system, which is already hyperactive in fibromyalgia patients. A gene variant that produces a “lazy” of the COMT enzyme could make matters worse by increasing norepinephrine (slowing its degradation). A signal amino acid substitution in the COMT gene that codes for the enzyme could alter pain processing and enhance pain sensitivity. Martinez-Lavin looked at this gene in two fibromyalgia patient populations: (1) those residing in Mexico and (2) those residing in Spain. Here is what he found:

the Spanish patients showed a significant increase in the “lazy” COMT gene that was associated with greater fibromyalgia symptom severity
the Mexican patients did not show an increase in the COMT gene variation, which may be explained by the more diverse genetic background
the lazy COMT gene is associated with greater pain sensitivity and its prevalence varies between different ethnic populations

The results are published in Arthritis Research & Therapy (2007) and laid the foundation for additional research grants and papers by Martinez-Lavin.

Role of Sleep Disturbance and Exercise on Symptoms and Cytokines
Principal Investigator: Benjamin Natelson, M.D. (New Jersey, USA)
(2006)

Two cytokines produced by the immune system (IL-6 and IL-8) promote inflammation and are known to disrupt sleep. When a healthy person exercises, these two cytokines ordinarily increase, but this study found that they significantly dropped during an exercise test. When subjects were subjected to sleep deprivation, IL-8 increased in the healthy group, but it dropped in the fibromyalgia group. “The results may suggest an element of cytokine dysfunction in the patients,” writes Natelson. His findings were published in 2010 in Clinical Vaccine and Immunology and 2013 Clinical Vaccine and Immunology. Natelson also received additional NIH funding to further his research.

Examining Spinal Cord/Brain for Glial Cell Activation/Involvement
Principal Investigators: Linda Watkins, Ph.D., and Dianne Lorton, Ph.D. (USA)
(2004)

The neurons in the CNS are the messengers of pain in fibromyalgia, but drugs that target the neurons do a poor job of containing the symptoms. They also cause too many side effects. Elevation of immune system cytokines in the blood and skin of fibromyalgia points to another player: the glia. These immune cells in the CNS can control the way neurons behave and are thought to be driving fibromyalgia pain. The best way to evaluate glial cells is by sampling post-mortem tissue. The aim of this study includes:

setting up a lab at Sun Health Research Institute (SNRI) with skilled neuroscientists to extract and evaluate glial cells taken from post-mortem donors
devise a system to examine and monitor prospective donors near SHRI
include methods for recruiting donors with other chronic painful conditions (because the characteristics of glia cell involvement in fibromyalgia needs to be distinguished from other chronic pains, such as low back pain and neuropathic)
devise a method for recruiting age-sex matched healthy controls for the project

Watkins and Lorton successfully set up the protocol for accomplishing the above goals. In addition, they began recruiting subjects for the study and clearly demonstrated “proof of concept” that donors could be evaluated and enrolled in this one-of-a-kind program. Based on their documented success, Watkins and Lorton received a second small grant from AFSA to expand the recruiting process. See the above project, Establishing a Fibromyalgia Tissue Donation Program, funded by AFSA in 2006.

Hippocampus, Dopamine, and Gray Matter in Fibromyalgia
Principal Investigator: Patrick Wood, M.D. (USA)
(2002)

The hippocampus is essential for cognition, stress control, and pain relief. Fibromyalgia patients have cognitive difficulties (fibrofog) and their symptoms are made worse by stress. These symptoms point to problems with the hippocampus, so Wood used brain imaging to evaluate this region of the brain. Comparing fibromyalgia patients to healthy controls, he found the following:

significant reduction in the concentration of N-acetylaspartate (NAA), a marker for neuronal density and function (reduced NAA means impaired neuron function in the hippocampus; results were found using MRS imaging technique)
reduced NAA correlated with greater fibromyalgia symptoms
reduced gray matter density in the hippocampus (using MRI) correlated with lower NAA in this area
the reduction in gray matter density corresponded to a reduction in dopamine levels in the hippocampus and the cingulate cortex (using PET imaging)
reductions in dopamine corresponded to reduced pain thresholds and decreased gray matter in fibromyalgia

Wood published his NAA findings in Journal of Pain (January 2009) and his gray matter/dopamine findings in Journal of Pain (June 2009).

Noradrenaline Deficient Mice a Model for Fibromyalgia
Principal Investigator: Luc Jasmin, M.D., Ph.D. (USA)
(2001)

Jasmin’s goal was twofold: (1) determine if a genetically modified mouse that cannot make norepinephrine (a transmitter that is low in the CNS of patients) can be used as an animal model for fibromyalgia, and (2) look at the relationship between norepinephrine, substance P, and opioids. Jasmin found the following:

the norepinephrine deficient mice were pain sensitive and did not respond as well to treatment with opioids (like fibromyalgia)
when substance P levels were antagonized (reduced) in the mice, their response to opioids greatly improved
the lack of norepinephrine led to increased substance P, but the mice lacked some symptoms of fibromyalgia, so they were not a good model for the disease
this study showed that low norepinephrine levels and high substance P (present in fibromyalgia) will significantly reduce the effectiveness of opioids … both the opioids that one takes orally and those that the body naturally produces

Jasmin’s findings were published in PNAS (2002) and provided the basis for an NIH grant.

Role of DNIC in Fibromyalgia Pain
Principal Investigator: Serge Marchand, Ph.D. (Canada)
(2000)

The diffuse noxious inhibitory control (DNIC) is a system in the spinal cord and brainstem that works to relieve pain. It is triggered when the body is subjected to a painful stimulus, perhaps an injury or a diseased joint. The effectiveness of the DNIC system (which is now called the conditioned pain modulation system or CPM) may not be working well in fibromyalgia patients. Marchand evaluated the efficacy of the DNIC/CPM in three groups: (1) fibromyalgia patients, (2) low back pain patients, and (3) healthy pain-free controls. Here is what Marchand found:

fibromyalgia subjects do not activate their DNIC system as much as low back pain patients and healthy subjects when subjected to a painful cold stimulus … the pain inhibitory system is not fully recruited and treatments to booster the serotonin and norepinephrine pathways involved should be tested – PAIN (2005)
Marchand also looked at the role of sleep disruption, depression, and anxiety on the efficacy of the DNIC/CPM system in fibromyalgia patients and found only sleep quality to play an important role – Open Rheumatology Journal (2011)
examining a larger group of fibromyalgia patients (96) and healthy controls (71), Marchand found that 40 percent of them experienced enhanced pain following the cold stimulus … this means the pain inhibitory system is severely impaired in a subgroup of fibromyalgia patients – PAIN (2016)

The lack of the CPM system efficacy varies significantly between patients, partly due to differences in sleep quality and likely many other factors that need to be studied. Marchand used the data from these studies to obtain a grant from the Canadian IHR.

Opioid Receptors in the Skin and Muscle of Fibromyalgia
Principal Investigator: Haiko Sprott, M.D. (Switzerland)
(1999)

Both the muscle and skin tissues of fibromyalgia patients hurt, so Sprott hypothesized that the opioid receptors in these tissues may be different or not functioning properly. Looking at muscle and skin biopsies in patients and controls, he found:

opioid receptors were shown for the first time to be present around muscle satellite cells, but the quantities were the same for patients versus controls
delta-opioid receptors were increased 59-fold in the skin of patients versus controls
kappa-opioid receptors were increased 21-fold in the skin of patients versus controls
the most common opioid medications target the mu-opioid receptors and their levels were the same in patients versus controls
Sprott suggests that topical opioids targeting the delta and kappa receptors may benefit fibromyalgia patients – unfortunately medications targeting delta opioid receptors are still in the development stage

Sprott published his muscle findings in Arthritis & Rheumatism (2003) and his skin findings in Arthritis & Rheumatism (2007). He used data from this study to obtain additional to study the pain regulatory mechanisms in fibromyalgia.

Chronic Effects of NGF in Spinal Cord of Fibromyalgia
Principal Investigator: Alice Larson, Ph.D. (USA)
(1998)

Nerve growth factor (NGF) is increased fourfold in the spinal fluid of fibromyalgia patients, but what is its role in generating the symptoms? Larson looked at this question in mice and human subjects, and found:

increasing NGF in the spinal fluid of mice caused pain hypersensitivity, but the mice did not show any of the other symptoms of fibromyalgia (sleep disorder, fatigue or sensitivity to stress)
Larson hypothesizes that mast cells in the nervous system (especially the thalamus) are responsible for the elevated NGF levels
evaluating other substances in the spinal fluid of fibromyalgia patients, Larson found increased pain-promoting amino acids, such as glycine and taurine, which correlated with symptoms and increased production of nitric oxide

Larson published her findings in PAIN (2000) and used this data to obtain an NIH grant.

Effect of Exercise on Temporal Summation of Pain in Fibromyalgia
Principal Investigator: Roland Staud, M.D. (USA)
(1998)

Temporal summation of pain is a phenomenon in which the same mild repetitive stimulus starts to be perceived as increasingly painful. It’s also called windup because the pain builds up and it is caused by activation of the NMDA receptors in the spinal cord that can amplify pain. Fibromyalgia patients often state that exercise (even mild) causes their pain to become worse, so Staud measured their degree of windup. He also attempted to answer many questions related to the windup phenomenon. Here are his findings:

exercise increased pain in fibromyalgia patients while it decreased pain ratings in the healthy controls (for the exact same level of exertion) … the pain inhibitory system kicked in for the controls but not the patients – Journal of Pain (2001)
the above study looked at aerobic exercise on a bicycle; the effects of isometric strengthening exercises produced similar results … the pain inhibitory system reduced discomfort in the controls and increased pain in the patients – PAIN (2005)
looking at the stimulus intensity use and the stimulus frequency, fibromyalgia patients required lower stimulus intensities and less frequent stimuli (the interval between each stimulus) to produce the same level of pain windup … increased activity in the spinal cord and activation of the NMDA receptors may contribute to these findings – PAIN (2004)
blocking the NMDA receptors in the spinal cord with a single dose of dextromethorphan reduced windup by the same percentage in the fibromyalgia patients and the healthy controls … meaning that windup may be maintained in patients by peripheral neurological inputs but dextromethorphan may be still be effective for reducing the degree of windup for patients – Journal of Pain (2005)
the number and intensity of peripheral pain areas is a strong predictor of a fibromyalgia patient’s overall pain, so future studies need to identify the source of the peripheral impulse input and its role in fibromyalgia – Rheumatology (2006)

Not only did Staud publish many papers, but his AFSA award also led to a large NIH grant.

Role of Cytokines in Fibromyalgia
Principal Investigator: Daniel Wallace, M.D. (USA)
(1998)

Three ctyokines were measured in the blood of patients and controls. In addition, blood cells were stimulated in culture to see if they produced more of these cytokines. Wallace published his results in Rheumatology (2001), which highlights the following:

IL-1R antibody and IL-8 were significantly elevated in the patient group, and the levels increased with duration of symptoms
when blood cells were stimulated in culture, IL-1R antibody, IL-8 and IL-6 production was significantly greater for the patient group

Sensitization and Chemical Sensitivities in Fibromyalgia
Principal Investigator: Iris Bell, M.D., Ph.D. (USA)
(1997)

Is the brain in fibromyalgia sensitized to substances? Bell exposed patients and controls to a sugar syrup they ingested once a week for three weeks. She measured each subject’s electroencephalogram (EEG) to detect the brain’s response to the sugar. Here is what she found:

patients had lower resting blood glucose levels and higher carbohydrate cravings
when exposed to the sugar syrup, patients exhibited increased alpha wave activity in the front midline of the cortex … these waves interfere with brain function

Bell published two reports, one about chemical intolerance in JCFS (2001) and the other about sugar sensitization in Journal of International Neuroscience (2001). Bell used the data from this study to obtain a large NIH grant to further her studies.

Limbic System in Abnormal Pain Perception in Fibromyalgia
Principal Investigator: Larry Bradley, Ph.D. (USA)
(1997)

Low intensity stimuli (not generally painful) were given to patients and controls while their brain blood flow was measured in the scanner. Regardless of whether the stimuli were painful or not, the brain blood flow in the patient group significantly increased in the limbic structures. This documents that heightened pain sensitivity is not imagined. Bradley presented the findings at the 2000 rheumatology meeting and used the data for a large NIH grant. He also incorporated it into a review paper on abnormal pain sensitivity in fibromyalgia in Current Rheumatology Reports (2001).

Pain-induced Basal Ganglia Changes – Fibromyalgia vs. Depression
Principal Investigator: Larry Bradley, Ph.D. (USA)
(1997)

People with fibromyalgia are often mislabeled as having depression, so Bradley looked at brain responses to stimuli in three groups: healthy, depressed and fibromyalgia. He presented the findings at the 2001 pain meeting and used the data with the above study to receive an NIH grant. Here is what Bradley found:

People with depression have normal pain thresholds and their brain imaging response to stimuli resembles that of healthy pain-free people
Both above findings are different for fibromyalgia patients

Controlled Trial of Dextromethorphan
Principal Investigator: Robert Bennett, M.D. (USA)
(1997)

Dextromethorphan is thought to block the NMDA receptors in the spinal cord that can amplify incoming pain signals. This theory was put to the test to see if the drug could reduce fibromyalgia pain. Bennett presented the results of his placebo-controlled trial at the 2000 rheumatology meeting and found:

25 mg of dextromethorphan taken twice daily significantly reduced pain in most patients and the side effects were mild

Melatonin in Fibromyalgia
Principal Investigator: Leslie Crofford, M.D. (USA)
(1996)

Melatonin sets the body’s sleep/wake cycle and triggers the production of cortisol. Crofford looked at these two hormones during a 24-hour cycle in fibromyalgia patients and healthy controls. She found:

nighttime melatonin production is higher in fibromyalgia
cortisol production significantly lags peak melatonin levels by 75 minutes

The results were published in Journal of Rheumatology in 1999 and served as the basis for an NIH grant.

Neuroendocrine Therapies for Fibromyalgia
Principal Investigator: Robert McMurray, M.D. (USA)
(1996)

Bromocriptine works to increase brain dopamine while melatonin increases serotonin levels. Both should also help with pain and sleep. McMurray separately tested 2.5 mg/night of bromocriptine and 6 mg/night of melatonin in a placebo-controlled trial. Here is what he found:

bromocriptine reduced pain in 26 percent of patients
melatonin reduced pain in 25 percent and sleep problems in 20 percent of patients
regardless of which therapy was used, responders could be identified by a doubling of their serum melatonin levels

Sleep, Immune and Endocrine Function in Fibromyalgia
Principal Investigator: Harvey Moldofsky, M.D. (Canada)
(1995)

Fibromyalgia patients have alpha brain waves that interrupt sleep, so Moldofsky looked at the impact of disrupted sleep on immune and hormone function. He presented his results comparing fibromyalgia to healthy controls at the 1998 rheumatology meeting. Moldofsky received additional funding to explore the connections, and below are his findings:

natural killer cells activity is dramatically decreased during the day and night
cortisol production is low (an adrenal hormone)
the sleep/wake body rhythms are significantly different (fibromyalgia patients are most energetic at 2 p.m. – a time when healthy people experience a lull)

Autonomic Function in Fibromyalgia
Principal Investigator: Daniel Clauw, M.D. (USA)
(1995)

Tilt-table testing, Holter monitoring of the heart, and blood sampling were used to assess autonomic system function. Clauw presented his results at the 1996 rheumatology meeting and in 1997 received a large NIH grant. Below are his findings:

tilt-table showed a significant drop in blood pressure and dizziness in 20 percent of patients compared to the controls
sympathetic and neurohormonal transmissions to the heart were significantly reduced in the patients
the autonomic nervous system in patients appears partially crippled in its ability to respond to challenges