Is Acupuncture Effective In The Treatment of Fibromyalgia?

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Is Acupuncture Effective In The Treatment of Fibromyalgia?

 

Literature Journal Review

by Andrew Pacholyk, L.Ac. MSTOM

 

 

Purpose/Rationale

The rationale behind this literature review is to take a look at the

current research that has been done on the topic of fibromyalgia, in

particular, the treatment of acupuncture on this disorder. This

review will take a comprehensive look at the research; current trends

in treatment for these symptoms and express the need for continued

work in this most timely area of research.

 

Fibromyalgia is a chronic disorder characterized by widespread

musculoskeletal pain, fatigue, and multiple tender points. " Tender

points " refers to tenderness that occurs in precise, localized areas,

particularly in the neck, spine, shoulders, and hips. People with

this syndrome may also experience sleep disturbances, morning

stiffness, irritable bowel syndrome, anxiety, and other symptoms.

The Merck Manual defines Fibromyalgia as used to describe several

related disorders. Various alternative terms for these disorders have

been used, including generalized fibromyalgia, which is 7 times more

common in women than in men, the pain and stiffness are widespread,

occurring throughout the body. Primary fibromyalgia syndrome is the

most common variation of generalized fibromyalgia; it usually occurs

in young or middle-aged women who have no associated or contributing

underlying disorder. Secondary fibromyalgia syndrome is a type of

generalized fibromyalgia and refers to fibromyalgia symptoms in a

person who has another underlying disorder that is causing the

fibromyalgia symptoms, such as hypothyroidism. Other disorders, such

as systemic lupus erythematosus or rheumatoid arthritis, may be

associated with fibromyalgia, but not be the underlying cause.

 

Localized fibromyalgia expresses as pain and stiffness occurring in a

particular area, or at a few sites, such as the jaw, neck, and/or

shoulder muscles. Localized fibromyalgia is somewhat more likely to

occur in men, possibly because they are more likely to engage in more

physically muscular activities in occupational or sports situations.

Sometimes, localized fibromyalgia gradually spreads to become

generalized fibromyalgia. Myofascial pain syndrome is a type of

localized or regional fibromyalgia which may occur in various sites

and differentiated as temporomandibular type and myofascial pain

syndrome. Previously, these disorders were collectively called

fibrositis or fibromyositis syndromes, but because inflammation is

not present, the " itis " suffix was dropped.

 

Both Eastern and Western medicine agree that insomnia is a key to

fibromyalgia. Western doctors prescribe sleeping pills. Chinese

medicine aims to nourish the Heart and Liver, which are the two most

important internal organs in regards to sleep, and to bring them into

balance with the Spleen. With Heart blood deficiency, people find it

difficult to fall asleep. With Liver Qi stagnation, sleep becomes

restless, with intense dreams and a tendency to wake up early in the

morning. Spleen and Heart deficiency would express as lying awake at

night worrying about job, children, finances…. In the morning one

would feel fatigued, with stiff, painful muscles.

 

In treating these conditions, the goals are to regulate and move

Liver Qi, harmonize the Liver and nourish the Spleen so it can do its

job of transformation and transportation. This is done with

acupuncture treatments combined with herbal formulas. Shu Gan Wan is

a formula, which breaks up Liver Qi stagnation. Xiao Yao Wan is a

formula used when a dysfunctional Liver is affecting the Spleen. An

herbal formula called Gui Pi Wan, is specifically designed for Spleen

and Heart deficiency. Calming exercise such as Tai Chi QiQong or

yoga can also promote balance and health. The length of time it

takes to see results from treatment depends on how serious the

symptoms are, but most people notice improvement after six to eight

treatments.(ii)

 

 

Epidemiology, Morbidity, Cost

 

According to the American College of Rheumatology, it's estimated

that 3 million to 6 million Americans are living with this

musculoskeletal disorder two thirds of them women, most of them white

and most between 20 and 60 years old when first affected.

Generalized fibromyalgia is 7 times more common in women than in men.

(i) Insomnia seems to be the most common thread between the

majorities of cases. Suffering from pain day in and day out, all

over the body plus fatigue, anxiety and depression are problems that

are encountered. There is no firm physical evidence of disease that

can be detected by blood tests or X rays. Doctors diagnose

fibromyalgia by testing 18 " tender points, " starting between the

shoulders. People complain they are tender all over the body, but

these areas, all where muscles attach to ligaments or bones, tend to

have pain with just the pressure of a thumb.

 

A major epidemiological study (iii) was conducted utilizing the

administrative claims data of a Fortune 100 manufacturer, which were

used to quantify direct (i.e., medical and pharmaceutical claims) and

indirect (i.e., disability claims and imputed absenteeism) costs

associated with fibromyaglia. A total of 4699 patients with at least

one fibromyaglia claim between 1996 and 1998 were contrasted with a

10% random sample of the overall beneficiary population. Employee-

only subsets of both samples also were drawn. Medical utilization,

receipt of prescription drugs, and annual total costs were

proportionately similar yet significantly greater among fibromyaglia

claims than the overall sample (with a proportional value of p <

0.0001). Total annual costs for fibromyaglia patients were $5945

versus $2486 for the typical beneficiary (with a proportional value

of p < 0.0001). 6% of these costs were attributable to fibromyaglia -

specific claims. The prevalence of disability was twice as high among

fibromyaglia employees than overall employees. For every dollar spent

on fibromyaglia -specific claims, the employer spent another $57 to

$143 on additional direct and indirect costs. Hidden costs of

disability and co-morbidities greatly increase the true burden of

fibromyaglia. Regardless of the clinical understanding of

fibromyaglia, when a claim for fibromyaglia is present, considerable

costs are involved.

 

 

Impact of Conventional Health Care

 

The burden of side effects from allopathic drugs is as numerous as

the types of drugs that are prescribed for fibromyalgia. Patients

who often take medications often experience side effects such as

nausea, drowsiness, or lightheadedness.

 

Analgesics are pain killers and can include over-the-counter

medicines such as aspirin and acetaminophen, or prescription-strength

pain pills like narcotics (opiates), codeine, Vicodin, Darvocet,

Oxycontin and Percocet. These medications do not alter the

fibromyalgia, but they can help take the edge off of pain.

 

Narcotic medications have potential for adverse side effects

including drowsiness, difficulty with concentrating, and addiction.

Many people with fibromyalgia are sensitive to codeine medicines,

which can cause nausea or an allergic reaction. Ultram can cause

allergic reactions in people sensitive to codeine, and a small number

of people taking Ultram have seizures.

 

Anti-inflammatory medicines include aspirin, nonsteroidal anti-

inflammatories (NSAIDs) such as ibuprofen, Naprosyn, Lodine, Daypro,

and the newer Cox-II inhibitors, and corticosteroids such as

prednisone or dexmethasone. The major side effect of the anti-

inflammatory drugs is bleeding from gastrointestinal ulcers. This

problem is more common the longer the medicine is taken.

 

The antidepressant medicines include tricyclics (Amitriptyline,

Nortriptyline, Doxepin, and Trazodone), and selective serotonin

reuptake inhibitors (Prozac, Zoloft, Paxil, Effexor, Serzone, and

Celexa). Zoloft and Paxil can cause sexual dysfunction. Some of the

newer medicines, Effexor and Serzone, for example, do not inhibit

sexual function. These medicines can treat pain and alter sleep and

mood disturbances seen in fibromyalgia.

 

The tricyclic medicines are effective, but frequent side effects

include dry mouth and drowsiness, extreme sedation and morning

hangover. The most common reported concern about using sleep

modifiers, especially benzodiazepams, is the habit-forming potential.

Ambien is reported to be less habit-forming but can cause rebound

insomnia when it's stopped. Some people report nightmares with these

medicines.

 

Anxiety is a common problem in fibromyalgia and contributes to pain,

muscle tension, and irritability. It can make depression and insomnia

worse. Various medicines including antidepressants and muscle

relaxants treat anxiety. Benzodiazepines such as Klonopin, Ativan,

and Xanax, are commonly used medicines. Possible side effects

include depression and decreased memory. Sometimes it is hard to

determine whether symptoms are due to fibromyalgia or are side

effects of medication. (iv)

 

 

 

Controversies In Research Publications

 

The following are a review of the most appropriate studies done on

the effects of acupuncture and fibromyalgia. The most apparent study

that kept coming up in viewing the research on this topic and the

studies and reviews most often referred to, is this study by Deluze,

et al, " Is acupuncture effective in the treatment of fibromyalgia? "

[1], which was a high quality study conducted in 1992 in Geneva,

Switzerland. This randomized controlled trial was out to examine

whether fibromyalgia patients got relief from real electroacupuncture

versus sham acupuncture. The sham acupuncture was designed to mimic

real acupuncture, but using nonacupuncture points and more

superficial needling insertion. The real acupuncture group found

significantly more relief (with a probability value of P < .05, Mann-

Whitney test) than the sham acupuncture group based on 5 of 8

outcomes that were measured. The main outcome measures used were:

pain threshold, number of analgesic tablets used, regional pain

score, pain recorded on visual analogue scale, sleep quality, morning

stiffness and patient and physician's evaluating appreciation. The

Mann-Whitney test is used in place of a two-sample t-test when the

populations are being compared, are not normal. The mean age range

of the patients was 48 years old. The mean duration of a

fibromyalgia diagnosis was 10.7 years. The inclusion criteria for

these patients were all under the 1990 guidelines of the American

College of Rheumatology. Out of the 70 participants, approximately

25% had no benefit, 50% experienced satisfactory benefit and the

remaining 25% had unexpectedly large improvements with almost

complete remissions. These percentages changed with intention-to-

treat analysis. 42% had no benefit, 39% had satisfactory benefit and

19% had unexpectedly large benefit. Only one individual in the sham

acupuncture had an unexpectedly large benefit. It is not known which

factors predisposed the individual to improvement. 15 patients

(21%) dropped out of the study. Those who dropped out, 11 were

related to the acupuncture procedure- 6 experienced symptoms of

exacerbation, 1 experienced transient ankle edema, 4 were

uncomfortable from the needle insertions. The remaining 4 who dropped

out, did not leave due to the acupuncture procedure. There was no

difference in reason or rate of dropouts as to whether real or sham

acupuncture was used. Also, dropouts did not differ from those who

completed the study on any baseline measures. The experimental

treatment consisted of 2 real electroacupuncture sessions (2-99Hz) 2

times per week for 3 weeks. The controlled treatments with sham

acupuncture consisted of 2 sham electroacupuncture sessions, 2 times

per week for 3 weeks. The study evaluated patients immediately after

the 3-week course of therapy and did not have a long term follow up.

 

A randomized controlled study was conducted in 1989 by Lautenschlager

et al [2, 9] in 1989 in Basel, Switzerland. The experimental

treatment consisted of 6 acupuncture treatments. The controlled

treatments consisted of 6 sham acupuncture sessions with an inactive

laser. The study evaluated patients immediately after the course of

therapy and found that the 3 patients who had had the real

acupuncture had significant improvement in 3 of the outcomes

measured, compared to the placebo group who received the sham

acupuncture. Outcome measurements showing improvement included pain

intensity, (with the probability value as P = .03 based on the

Wilcoxon test which is a test to see whether the values in two

samples differ in size), localized pain (with the probability value

as P = .009, Wilcoxon test) and pain threshold (with the probability

value as P = .008, t test). Three-month follow up data was presented

which included data from a nonrandomized pilot study. It was

determined that no significant difference between acupuncture and the

placebo group could be determined at a 3 month follow up.

 

Chen et al [9,10] performed a high-quality randomized controlled

study with a combination of low and high frequencies with

electroacupuncture, consistent with laboratory data suggesting that

optimal pain relief is achieved by combining low (2-4 Hz) and high

(50-100 Hz) frequencies. The combined frequencies are believed to

complement each other (ie, low-frequency acupuncture is associated

with endorphin release and cumulative effects, and high-frequency

acupuncture is associated with serotonin release and short-lived

effects). For a syndrome such as fibromyalgia, where the cumulative

as well as serotonergic effects are extremely helpful, the long term

effects should be studied in order to sustain the outcome

measurements related to the pain associated with this disorder.

 

A prospective cohort study conducted by Sprott et al [3] in 1996 in

Germany looked at 29 patients with fibromyalgia to examine whether

the biochemical as well as clinical, indicators could be improved

with the use of acupuncture. The mean age range of the patients was

48 years old. The mean duration of a fibromyalgia diagnosis was 6.1

years. The inclusion criteria for these patients were all under the

American College of Rheumatology. After acupuncture, the outcome

measures of pain relief, pain threshold, including sleep quality,

improved (with a probability value of < .01, statistical test was non

specific), as did the biochemical markers of serum serotonin and

serum substance P. Sprott et al determined in the results that the

biochemical improvements confirm the involvement of pain modulating

molecules in fibromyalgia. This study had only an immediate follow

up done. No other parameters of the treatment experiment were

reported.

 

Many patients with fibromyalgia often experiment with several

different healing modalities as well as many pharmacological drugs.

Antidepressants are often prescribed to patients with fibromyalgia.

Passotti et al [4, 9] designed a prospective cohort study with

multiple arms in 1990 in Italy utilizing three groups of fibromyalgia

patients. One group received acupuncture alone. Another group

received acupuncture plus Amitriptyline, an antidepressant. Yet

another group received conventional physiatry. Equivalence between

groups was neither intended or achieved; therefore, the study was

classified as a prospective cohort study with multiple arms.

Patients with the most severe fibromyalgia symptoms were placed in

the acupuncture plus antidepressant group. Manual acupuncture alone

was given every 5 days for 8-10 treatments in both the acupuncture

alone group and the second group who received acupuncture plus

Amitriptyline. After the treatments, the outcome measures of pain

relief and tender points were statistically better in the acupuncture

alone group and second group who received acupuncture plus the

antidepressant (with a probability value of < .05, t-test) versus the

conventional physiatry group. The treatments within the conventional

physiatry group were not reported in this study. There was an

immediate follow up as well as a 1, 3, 6 and 9-month summary. At the

6-month follow up, the acupuncture alone group continued to remain

with better results (with a probability value of < .05, t-test) than

the conventional physiatry group on the outcome measures of pain

measurements as well as psychological measures of depression,

hostility, anger and somatatization. At the 6-month follow up for

the acupuncture plus the antidepressant (with a probability value of

< .05, t-test) versus the conventional physiatry group, only

significant improvement remained on the outcome measure of pain

threshold, not on any psychological index.

 

A variety of symptoms can often be associated with fibromyalgia

patients. A group of 35 patients with a specific diagnosis of

trapezius fibromyositis were studied by Radaelli et al. [5, 9] in

Italy in a prospective cohort study in 1978. These 35 patients were

given 5 sessions of electroacupuncture using between 50-70 Hz on

alternate days. The mean age range between these patients was

between 19-72 years old. All these patients had used different

healing modalities as well as many pharmacological drugs, none of

which were specified as to which drugs or which modalities were used

on the past. After an average of 5 sessions of electroacupuncture,

29 (82.8%) patients received sufficient pain relief to terminate

therapy. 3 (8.6%) patients received initial relief but later returned

to therapy because of relapses. 2 (5.7%) patients reported only mild

relief of symptoms while 1 (2.9%) reported no relief. The outcome

measurements most improved were that of pain relief and range of

motion. Follow up was only reported immediately after the study was

complete.

 

In 1977 at the Riverside Methodist Hospital in Ohio, Waylonis et al

[6] performed a retrospective cohort study by sending out a postal

survey to fibromyalgia patients whom had a variety of therapeutic

modalities at their clinic. These modalities included acupuncture,

medications, cortisone injections, physical therapy, whirlpool

treatments, ultrasound, diathermy and manipulation. A total of 62

people were sent the survey poll and 39 patients responded. The mean

age of the patients was 39 years old. Their mean length of follow up

time at the completion of the survey poll was an average of 19.6

months. More than half of the survey responders had between 4-10

therapeutic modalities. Patients were asked to specify which

therapeutic modalities (a) gave them the best results, (b) the

longest lasting results, © the estimated duration of benefits and

(d) the least results. Acupuncture was rated as providing the best

and the longest pain relief by 29 (46%) of the responding patients.

Patients were asked to evaluate the extent of the relief specifically

from acupuncture. Here, 8 (20.5%) reported total relief, 18 (46.2%)

reported partial relief of 50%-90% improvement, 5 (12.8%) patients

reported borderline relief of 10%-40% improvement, 7 (17.9%) patients

had no relief and 1 (2.6%) patient had aggravated symptoms. The

duration of relief from acupuncture varied from less than a day,

which was in 7 patients, to 10 months or longer which was seen in 6

patients.

 

Collagen and muscle pathology in fibromyalgia patients has been

looked at in several studies. There is some research suggesting that

there is a disorder of collagen

metabolism in fibromyalgia patients. The first of two studies I

found, were conducted by Gronemann ST et al [7] in 2003. Their

objective was to measure collagen concentration and search for muscle

pathology in muscle non-tender-point areas from fibromyalgia

patients. Muscle biopsies were obtained from m. vastus lateralis of

27 selected, female fibromyalgia patients, and from 8 age-matched

female control subjects. Amino acids were determined by a high-

performance liquid chromatography (HPLC) and electron microscopy was

performed. The studied results showed patients had lower

hydroxyproline and lower total concentration of the major amino acids

of collagen than the control group. No significant difference was

seen in the concentration of the major amino acids of myosin or of

total protein. Electron microscopy showed no significant differences

between fibromyalgia patients and controls although atrophied muscle

fibrils occurred in fibromyalgia patients only, but frequencies were

not significantly different. They determined that fibromyalgia

patients had a significantly lower amount of intramuscular collagen.

This may lower the threshold for muscle micro-injury and result in

non-specific signs of muscle pathology.

 

The second of these studies on collagen was researched by Sprott et

al [8] to determine if abnormal collagen metabolism is a

characteristic of fibromyalgia. Skin biopsies were taken from the

trapezius area of 8 patients with fibromyalgia. All patients had the

diagnosis of fibromyalgia according to the American College of

Rheumatology criteria. Urine was collected under standardized

conditions from 55 control subjects and 39 patients with

fibromyalgia, and serum was obtained from 17 controls and 22 patients

with fibromyalgia. Pyridinoline (Pyd), an indicator of connective

tissue disease, and deoxypyridinoline (Dpyd), an indicator of bone

degradation, both of which represent products of lysyl oxidase—

mediated crosslinking in collagen, were analyzed by ion-paired and

gradient high-performance liquid chromatography (HPLC) methods with

fluorescence detection. Levels of hydroxyproline (Hyp), a collagen

turnover marker, were also measured. The findings were related to

creatinine levels, and the Pyd:Dpyd ratio was determined. Highly

ordered cuffs of collagen were observed around the terminal nerve

fibers by electron microscopic examination of biopsy tissue from all

8 patients with fibromyalgia, but were not observed in any of the

control skin samples. The Pyd:Dpyd ratios in the urine and serum and

the Hyp levels in the urine were significantly lower in patients with

fibromyalgia than in the healthy control group.

 

 

Summary

 

The reviewed studies reveal that acupuncture is a therapeutic

modality that has shown good benefits in the outcome measurements of

pain relief for fibromyalgia. Electroacupuncture had shown even

greater results with pain threshold, regional pain scoring and sleep

quality. A combination of both high frequencies, associated with

serotonin release - short-term effects and low frequencies,

associated with endorphin release - cumulative effects is optimal for

pain relief. The results of one high quality study suggest that real

acupuncture is more effective than sham acupuncture. Further high

quality studies need to be researched in order to show more long-term

clinical benefits of acupuncture.

 

 

 

Annotated Bibliography

1.Deluze C, Bosia L, Zirbs A, et al. Electroacupuncture in

fibromyalgia: results of a controlled trial. BMJ 1992;305(6864):1249–

52. The real acupuncture group found significantly more relief than

the sham acupuncture group based on 5 of 8 outcomes that were

measured. The study evaluated patients immediately after the 3-week

course of therapy and did not have a long term follow up.

 

2. Lautenschlager J, Schnorrengerger CC, Muller W. Fibromyalgia

Syndrome. Dtsch ZschrAkup 1989; 6:122-8 The controlled treatments

consisted of 6 sham acupuncture sessions with an inactive laser. The

study evaluated patients immediately after the course of therapy and

found that the 3 patients who had had the real acupuncture had

significant improvement in 3 of the outcomes measured, compared to

the placebo group who received the sham acupuncture.

 

3. Sprott H, Franke S, Kluge H, Hein G. Pain treatment of

fibromyalgia by acupuncture. Rheumatol Int 1998;18:35–6. After

acupuncture, the outcome measures of pain relief, pain threshold,

including sleep quality, improved as did the biochemical markers of

serum serotonin and serum substance P. Sprott et al determined in

the results that the biochemical improvements confirm the involvement

of pain modulating molecules in fibromyalgia.

 

4. Pasotti D, Montanarri E, Capobianchi B. Acupuncture and Primary

Fibromyalgia Syndrome. G Ital Riflessot Agopunt 1990; 2:23-31 After

the treatments, the outcome measures of pain relief and tender points

were statistically better in the acupuncture alone group and second

group who received acupuncture plus the antidepressant versus the

conventional physiatry group. The treatments within the conventional

physiatry group were not reported in this study.

 

5. Radaelli E, Buzzi GP. Treatments of Acupuncture for Trapezius

Fibromyalgia. Min Med 1978; 69:3017-9 After an average of 5 sessions

of electroacupuncture, 29 patients received sufficient pain relief to

terminate therapy. 3 patients received initial relief but later

returned to therapy because of relapses. 2 patients reported only

mild relief of symptoms while 1 reported no relief.

 

6. Waylonis GW. Long-term follow-up on patients with fibrositis

treated with acupuncture. Ohio State Med J 1977;73:299–302. Patients

were asked to evaluate the extent of the relief specifically from

acupuncture. Here, 8 reported total relief, 18 reported partial

relief of 50%-90% improvement, 5 patients reported borderline relief

of 10%-40% improvement, 7 (17.9%) patients had no relief and 1

patient had aggravated symptoms. The duration of relief from

acupuncture varied from less than a day, which was in 7 patients, to

10 months or longer which was seen in 6 patients.

 

7. Gronemann ST, Ribel-Madsen S, Bartels EM, Danneskiold-Samsoe B,

Bliddal H Collagen and muscle pathology in fibromyalgia patients.

Rheumatology (Oxford). 2003 Jul 16 The Parker Institute, Department

of Rheumatology, Frederiksberg Hospital, H:S

University Hospital. Fibromyalgia patients had a significantly

lower amount of intramuscular collagen. This may lower the threshold

for muscle micro-injury and thereby result in non-specific signs of

muscle pathology.

 

8. Haiko Sprott, Andreas Muller, and Hartmut Heine, Collagen

Crosslinks In Fibromyalgia - Arthritis & Rheumatism, Lippincott-

Raven Publishers Vol. 40, No. 8, August 1997, The American College of

Rheumatology. Highly ordered cuffs of collagen were observed around

the terminal nerve fibers by electron microscopic examination of

biopsy tissue from all 8 patients with fibromyalgia, but were not

observed in any of the control skin samples. The Pyd:Dpyd ratios in

the urine and serum and the Hyp levels in the urine were

significantly lower in patients with fibromyalgia than in the healthy

control group.

 

9. Berman BM, Ezzo J, Hadhazy V, Swyers JP. Is acupuncture effective

in the treatment of fibromyalgia? Complementary Medicine Program,

University of Maryland School of Medicine, Baltimore 21207, USA. J

Fam Pract. 1999 Mar;48(3):213-8. The limited amount of evidence

suggests that real acupuncture is more effective than sham

acupuncture for improving symptoms of patients with fibromyalgia.

However, because this conclusion is based on a single high-quality

study, further high-quality randomized trials are needed to provide

more data on effectiveness.

 

10. Chen XH, Guo SF, Chang CG, Han JS. Optimal conditions for

eliciting maximal electroacupuncture analgesia with dense and

disperse mode of stimulation. Am. Journal Acupuncture 1994; 22: 47-

57 Electroacupuncture had shown even greater results with pain

threshold, regional pain scoring and sleep quality. A combination of

both high frequencies, associated with serotonin release - short-term

effects and low frequencies, associated with endorphin release -

cumulative effects is optimal for pain relief.

 

 

 

i. Fibromyalgia Syndromes. The Merck Manual of Medical Information--

Second Home Edition Sec 5, Ch.74

 

ii. Fybromyalgia -The American Academy of Acupuncture and Oriental

Medicine. www.aaaom.org

 

iii. Economic cost and epidemiological characteristics of patients

with fibromyalgia claims. J Rheumatol. 2003 Jun;30(6):1318-25.

Robinson RL, Birnbaum HG, Morley MA, Sisitsky T, Greenberg PE,

Claxton AJ. Eli Lilly and Company, Indianapolis, Indiana, USA. PMID:

12784409 [PubMed - in process]

 

iv. Pellegrino, Mark, MD; Prescribed Medications for Fibromyalgia:

2001 Mark J. Pellegrino, M.D., and Anadem Publishing, Inc.