“Anyone can have an idea,” says Yunus, “but it is the proof of it through hard work that can turn the world around.” Due to the efforts of Dr. Yunus and others, the world is finally beginning to see FM in a completely different light!
Stress, Anxiety & Depression
Ten years after Dr. Yunus published the first controlled study of the clinical characteristics of FM, the role of psychological factors is still being debated. There are people, who, according to Yunus, are inclined to say that “FM is nothing, it’s all psychological.” Then refuting these blame-it-on-the- patient theories, he points to the pain of cancer.
“I do not know of a more organic (visible under the microscope) cause of pain than that of cancer, and it is definitely known to be increased and aggravated by psychological factors — including depression, anxiety and stress. FM is no exception.”
Yunus took 103 FM patients and classified them into three psychological subgroups using the MMPI: (1) normal profile, (2) typical chronic pain profile, and (3) psychological disturbance profile. Categories (1) and (3) each accounted for one fourth of the patient group while most patients were found to fit into the chronic pain profile. Dr. Yunus reasoned that if the patient’s psychological status was playing a major role in their condition, then those in category (3) should have more severe or frequent symptoms, or a greater number of tender points than those in the other two categories.
As it turned out, the central features of FM, namely the number of tender points, fatigue and poor sleep did not correlate with psychological status. The same held true for the associated symptoms of swollen tissues in the extremities and paresthesias (numbness and tingling feelings). Given that all participants were selectively referred to Dr. Yunus’ clinic because their primary care physician was unable to help them, there is an inherent problem of referral bias in this study (perhaps over-representing those with psychological problems) — a situation that even Yunus openly acknowledges. Such a bias may explain why a quarter of the patients had significant psychologic distress. However, the report of Yunus’ study published in the January 1991 issue of “Arthritis & Rheumatism” stated the following conclusion: “The central features of FM are independent of the psychological status and are more likely related to the FM itself. However, pain severity may be influenced by psychological factors.”
So often FM patients are labeled as having a stress-related sleep disorder — once again implying that stress is at the root of their problems. While more experiments are needed in the area of sleep, a 1989 article by Yunus (J. Rheumatol. 16:62-71, suppl 19) casts doubt on this claim. “In this paper,” says Yunus, “we analyzed the patient-administered questionnaire about poor sleep, and actually, anxiety and stress did not correlate with the poor sleep… That doesn’t mean that stress does not play a role. Stress may be important, but it does not play the primary or predominant role. It’s not an invariable cause, that’s for sure.” For patients who are tired of being told that their symptoms are all stress- related, Dr. Yunus’ comments are most welcome and serve to reinforce what most patients believe in their hearts. However, there is a very important message that Yunus wished to relay: “You shouldn’t ignore stress or depression because they both may be acting as aggravating factors…This is true of all chronic pain disorders.”
Referring back to Dr. Yunus’ 1989 report in which two control groups were used (77 patients with rheumatoid arthritis and 67 healthy individuals), he made an interesting point: “Anxiety and stress aggravated the pain symptom of FM but the same results were also found in the rheumatoid arthritis group without any significant differences between the two groups. You can plug in almost any of the chronic diseases, including cancer, and come up with similar results.”
Dr. Yunus has combed through the cancer literature because many physicians cling to this notion that FM is a predominantly psychological illness in a disturbed group of people. He has even come up with a new name for these doctors: Disturbed Physician Syndrome, or DPS for short.
“DPS people are trouble because of their preoccupation that FM patients are psychologically disturbed. It is not the FM patients who are disturbed, it is the physicians who are psychologically disturbed because they ignore the data, and whatever data there is, they manipulate it to say what they want it to say.”
Dr. Yunus suspects that DPS is less common among rheumatologists and those physicians who have taken the time to learn more about FM — although only time will tell.
Summing it up, the history of FM has been colored by false accusations that this syndrome is none other than a problem of stress, anxiety or depression. These all are aggravating factors and have been used to camouflage the real cause of FM, which Yunus and several other modern-day researchers believe to be aberrant neurotransmitter mechanisms, perhaps in genetically predisposed individuals.
Two other syndromes that frequently occur in FM patients are irritable bowel syndrome (IBS) and chronic headaches. Not only do these two conditions share many demographic (mostly young to middle aged women) and clinical features with that of FM as Yunus pointed out in 1984 (Comprehensive Therapy, Vol. 14, p. 8), they also have in common a muddled history full of claims that the patients’ psychological status is to be blamed.
“If you go to the IBS and chronic headache literature,” explains Dr. Yunus, “you will find that the story is the exact replica of the FM syndrome. In other words, there is a subgroup of patients in the 20-30% range whose symptoms are in fact aggravated by anxiety, stress and depression.”
Referring back to Dr. Yunus’ 1989 paper in The Journal of Rheumatology, IBS occurred in 41% of the 113 FM patients sampled, and chronic headaches of moderate to severe degree showed up with a frequency of 56% — as compared with 1% and 14%, respectively, of 77 rheumatoid arthritis (RA) patients. To assist the large number of FM patients plagued by these two problems, they are discussed in more detail below.
Irritable Bowel Syndrome
Back in the days when FM was viewed as a 2-dimensional syndrome of tender points and sleep disturbance, Yunus added a third dimension: associated functional disorders such as IBS. “I was involved in doing research in IBS in the 1970’s,” says Yunus, “and found that a lot of my patients also had muscle aching.” Although he didn’t know the significance of this at that time, he later connected the two syndromes while involved in FM research, and discovered that a large number of his FM patients had IBS!
Earlier this year (1991), Drs. Triadafilopoulos and Goldenberg, of Boston, MA, duplicated Yunus’ finding that FM and IBS frequently coexist. 73% of the FM patients in their study reported altered bowel function as compared to 37% of a degenerative joint disease (DJD) control group. Specific bowel complaints among the 123 FM patients were: alternating diarrhea and constipation (63%), frequent abdominal pain (64%), abdominal gas (59%), nausea (21%), diarrhea alone (9%), and constipation alone (12%). Half of the FM patients, compared to one-forth of the DJD controls, felt that their IBS was worse during exacerbations of their musculoskeletal disease, as was earlier noted in some patients by Yunus.
Flipping the evaluation of IBS symptoms in FM patients around, another research team from Ireland recently reported that 65% of their IBS patients met the criteria for FM. And, a five-year old study indicates that many other non- bowel related problems occur in IBS patients, such as painful menstruation (68%), PMS (69%), urinary problems (50%), back pain (61%), headaches (31%), poor sleep (30%), and constant fatigue (63%). Given that these symptoms are often found in FM as well, it seems possible that a common pathogenic mechanism may be involved in both syndromes.
The current theory about IBS is that it’s due to an abnormal myoelectric activity of the gut muscles with slow rhythmic waves, causing the contents of the bowel to move slowly through the GI tract. For reasons unknown, the slow wave contractions usually occur in IBS patients, at a rate of about 3 cycles per minute versus a normal cycle of 6 per minute. This abnormal contraction rhythm can give rise to constipation as well as cramping type of abdominal pain. In the process, the slow myoelectric activity can force gas to be trapped, making a patient feel bloated. Patients with diarrhea often have lower than normal pressure waves (i.e., weak GI muscle contractions), whereas those with predominant pain have high-amplitude pressure waves in the colon.
IBS may seem like a measly problem of indigestion, but it is really a lot more complicated than that. According to Dr. Yunus,
“Just as the muscle and other tissues in FM patients tend to be super sensitive to stimuli like pressure – that’s why you have tender points – the same is also true of IBS. If you distend their sigmoid colon, with air for example (or exert moderate pressure on it), they will have excruciating pain beyond the level that normal controls would have. I was very struck with this finding during sigmoidoscopy of IBS patients, as compared with those with ulcerative colitis,” Yunus recalls. “A lot less pressure is required to produce pain in the IBS patient versus the normal control subject.”
For the most part, traditional treatment approaches to IBS have been directed at the bowel, such as laxatives, antidiarrheals, alterations in diet and stress reduction. A more detailed explanation of these self-help remedies may be obtained from “Learning to Live with Chronic IBS” by Norra Tannenhas. The publisher is Dell, and it costs $3.50 in the U.S. and $4.50 in Canada.
When it comes to research approaches to treatment, Yunus states, “I think the IBS researchers are really barking up the wrong tree. They are studying the target organ, which is the gut. It is fine to pursue this avenue in the way that we have studied the muscles in FM, but I think that they are missing the primary link. I suspect the gut is regulated by neurotransmitters and that is why Elavil (amitriptyline) has been documented to work well with IBS.”
Looking at all of the syndromes associated with FM, such as IBS, chronic headaches, and perhaps others, Yunus states: “The common denominator to them may well be neurotransmitter abnormalities and serotonin is one of them — an important one — but I do not believe the only one.”
Augmenting this neurotransmitter theory, a brain-gut neuro-peptide called cholecystokinin (CCK) has also been implicated in IBS. CCK is present in the limbic system, an area of the brain that was discussed in the last newsletter issue as possibly playing a role in FM/CFIDS. This neurotransmitter is released into the gut so that the GI tract muscles will contract and move the digestion products through it. However, if the CCK control mechanisms in the brain are disrupted, then the symptoms of IBS could result. In addition, abnormalities of other neurotransmitters, such as serotonin (which is thought to be a problem in FM), may work to amplify the pain of IBS.
Like FM, IBS is a complex syndrome. Drugs aimed at partially blocking the effects of CCK (eg., those in the benzodiazepine category such as Xanax and Klonopin) might be of help. Also, a June 1991 report in “Digestive Diseases and Sciences,” which attempted to pin down the neurotransmitters involved in altering the myoelectric activity, indicated that both acetylcholine and substance P dramatically decreased the slow wave cycle generation in the canine gut. Aside from Elavil’s beneficial effect on serotonin, it may also block the negative impact of acetylcholine and this could explain why it works in IBS treatment. A substance P blocker, somatostatin, is currently under investigation in FM because high levels of this transmitter have been found in the spinal fluid of this patient group. The elevation of substance P needs to be examined further, but it does provide another possible link between IBS and FM.
Migraine and tension-type headaches are seen frequently in FM patients. A good reference book on the subject geared towards patients is published by Consumer Reports and called “The Headache Book.” (Cost is $14.95 in the U.S.)
Migraine produces a one-sided, throbbing head pain and usually a range of other symptoms such as nausea and hypersensitivity to light and sound. A variety of conditions or substances can trigger a migraine attack, including certain foods, alcohol, caffeine, menstruation, and hormonal changes. Even stress has been shown to provoke an attack, but none of these triggers actually cause the headache — they only serve to aggravate an underlying condition.
To better understand what might be causing a migraine, it is important to have a clear picture of the sequence of events thought to lead up to it. Preceding an attack, the neurological activity in certain centers in the brain may be reduced, resulting in a slightly diminished blood flow to these areas. Then 20 to 30 minutes later, the headache pain begins when the blood vessels in the brain swell and allow the seepage of irritating chemicals into the surrounding tissues. These chemicals activate nerve endings, which in turn, transmit the pain.
While the exact etiology of migraine is not clear, the problem may be related to genetics and is known to involve serotonin, and possibly, norepinephrine and substance P. During the headache phase of migraine, reduced levels of serotonin have been noted in the blood. Ironically, low serum serotonin levels have also been found in FM.
Drug treatments for migraine fall into four categories: (1) medicines aimed at halting the headache mechanism, (3) antinausea agents, (3) painkillers and (4) preventive measures. Ergotamine tartrate is the drug most commonly used to stop a severe migraine attack before it fully develops. It is thought to constrict the blood vessels and it may have a beneficial effect on serotonin as well. Unfortunately, it can produce many unwanted side effect. Reglan is frequently prescribed as an antinausea agent. Aspirin, acetaminophen and ibuprofen may help reduce the painful aspect of migraine as well as other more powerful prescription painkillers. Even caffeine has been found to have an analgesic (pain fighting) effect, but patients should be cautioned that too much caffeine might precipitate a migraine while an occasional small dose can sooth it.
The most promising preventive headache measures involve the use of those drugs that boost serotonin levels in the central nervous system. Many antidepressants and benzodiazepines can increase the availability of serotonin (see last issue). Unfortunately, these drugs typically alter more than just the serotonin and can produce undesirable side effects. However, several medications that selectively increase serotonin are currently being tested.
Tension-type headaches are not necessarily related to psychological status or muscle tension. It is simply the name given to the most common type of head pain. These headaches usually produce a sensation of tightness or pressure across the forehead, on both sides of the head, at the back of the neck, or even extending down to the shoulders. As in FM, stress or depression may aggravate (not cause) tension-type headaches, as can a hot and humid day.
Aside from minimizing stress and other aggravating factors, two types of medications may be used on a regular basis, when headaches are a chronic problem. Nonsteroidal anti-inflammatory drugs (NSAIDS), such as ibuprofen or prescription strength medicines (naproxen, piroxicam), may fight pain and reduce the inflammation that can contribute to the pain. Central nervous system acting serotonin boosters, which were mentioned in the last issue, can also provide beneficial results.
Other Associated Syndromes
Along the same lines as IBS, painful bouts of an upset stomach (dyspepsia) or irritable bladder may relate to a problem of hypersensitivity to being distended. A January 1991 article on dyspepsi indicates that the pain of this disorder may be due to a lower pain threshold during gastric distention (Dig. Dis. Sci., Vol. 36). In addition, Daniel Wallace, M.D., of Los Angeles, found that female urethral syndrome occurred in roughly 10% of FM patients (J. Rheumatol. 17:2, 1990). This syndrome is characterized by urinary urgency, urethral pain and discomfort in the surrounding area in the absence of infection. As in FM, tender points are present, but localized to the bladder area, and like FM, it responds to similar therapies designed to alter neurotransmitter levels.
Other syndromes that occur in a significant portion of FM patients include temporomandibular dysfunction syndrome (see Oct. ’90 issue), mitral valve prolapse syndrome (see Jan. ’90 issue), premenstrual syndrome (see last issue) and a related problem of primary dysmenorrhea, which causes a cramping pain in the pelvic area during the menstruation phase of the cycle. Dr. Yunus in his 1989 Journal of Rheumatology article found that 45% of FM patients had primary dysmenorrhea as compared with 17% of the normal controls and 12% of the RA patients.
While the exact cause of these associated syndromes is not known, therapies aimed at changing neurotransmitter levels, particularly serotonin, are meeting up with some success. One can only speculate that their relationship with FM is that of abnormal brain chemistry regulation. “Clearly, this is an exciting area for future research,” Yunus concludes with enthusiasm.