Integrative Approaches

to Fibromyalgia
Part 1
Clinical Characteristics and Pathophysiology of Fibromyalgia
By Lesley M. Arnold, MD

Part 2
Treatment of Fibromyalgia
By Melinda Ring, MD

This activity is supported by an educational grant from Lilly USA, LLC. For further information concerning Lilly grant funding,
visit www.lillygrantoffice.com. This activity is equally supported by an educational grant from Pfizer Inc.
 TITLE
Integrative Approaches to Fibromyalgia
ACTIVITY TYPE
Monograph with 10-question posttest
RELEASE DATE
April 15, 2010
EXPIRATION DATE
April 15, 2011
TARGET AUDIENCE
This continuing medical education activity is intended for
members of the American Academy of Pain Management,
primary care physicians, and other healthcare professionals
who can take advantage of AMA PRA Category 1 Credit™.
STATEMENT OF NEED
Fibromyalgia (FM) is a chronic pain syndrome whose
diagnosis and treatment are complex and challenging to
many clinicians. Although no recent prevalence studies
of FM in the US have been published, a recent analysis
estimates that approximately 5 million adults over 18
years of age have primary FM (1). In addition, healthcare
utilization in FM presents a sizable economic burden—mean
annual expenditures for FM patients determined through a
retrospective cohort analysis of administrative healthcare
claims were US$10,911 (2). Furthermore, FM patients have
a greater comorbid burden of most conditions as compared to
patients with rheumatoid arthritis, and healthcare utilization
increased when both conditions were present (2).
Studies internationally (3-6) report inaccuracies in FM
diagnoses by primary care and family physicians.
Although the physicians in each sample were aware of
most FM-related symptoms, there were practice gaps present
in regard to the ACR classification criteria (7), treatment
modalities, and prognosis.
A 2008 study, which sought to identify and clarify
the clinical domains of FM from the physician and
patient perspectives (8), argued that perhaps “the most
knowledgeable ‘expert’ impacted by a disease or condition is
the patient living with the disease and experiencing its effect
daily.” While interdisciplinary patient-centered care focuses
on the mind and body, integrative care also brings attention
to the spirit. Considering that prayer is the most common
complementary therapy, studies have shown that religion
and/or spirituality contribute to well-being and coping in
patients with chronic pain and fatigue (9,10). Ultimately, a
comprehensive, integrative care program for the patient with
FM that recognizes body, mind, and spirit will encourage
favorable outcomes.
2
A 6-hour FM track took place at the Academy’s 2008 Annual
Clinical Meeting. Results of pre- and posttests indicate
misconceptions about FM. For example, almost 20% of
participants thought that morphine has been effective for FM in
published trials both before and after a course on pharmacologic
management. In addition, 30% of the audience in a presentation
on exercise therapy did not believe that adding endurance with
cardiovascular aerobic fitness exercise reflected appropriate
exercise progression for FM patients. Also, only 40% of
the audience was aware that 66% to 99% of patients seek
complementary and alternative therapies to manage their FM.
The Academy also distributes a needs assessment survey at the
meeting that contains lists of topics, modalities, behavioral
interventions, and professional issues in pain management.
Attendees are asked to indicate the extent to which educational
programming in the different areas would improve their practice.
FM ranked number 6 (out of 18 topics) among physicians,
physician assistants, nurse practitioners, and nurses (pooled data).
References
1. Lawrence RC, Felson DT, Helmick CG, et al. Estimates of
the prevalence of arthritis and other rheumatic conditions in
the United States: Part II. Arthritis Rheum. 2008;58(1):26-35.
2. Silverman S, Dukes EM, Johnston SS, Brandenburg
NA, Sadosky A, Huse DM. The economic burden of
fibromyalgia: comparative analysis with rheumatoid
arthritis. Curr Med Res Opin. 2009;25(4):829-840.
3. Buskila D, Neumann L, Sibirski D, Shvartzman P.
Awareness of diagnostic and clinical features of
fibromyalgia among family physicians. Family Practice.
1997;14(3):238-241.
4. Gamez-Nava JI, Gonzalez-Lopez L, Davis P, Suarez-
Almazor ME. Referral and diagnosis of common
rheumatic diseases by primary care physicians. Br J
Rheumatol. 1998;37(11):1215-1219.
5. Fitzcharles MA, Boulos P. Inaccuracy in the diagnosis
of fibromyalgia syndrome: analysis of referrals.
Rheumatology (Oxford). 2003;42(2):263-267.
6. Shleyfer E, Jotkowitz A, Karmon A, Nevzorov R, Cohen
H, Buskila D. Accuracy of the diagnosis of fibromyalgia
by family physicians: is the pendulum shifting? J
Rheumatol. 2009;36(1):170-173.
7. Wolfe F, Smythe HA, Yunus MB, et al. The American
College of Rheumatology 1990 criteria for the classifica-
tion of fibromyalgia. Report of the Multicenter Criteria
Committee. Arthritis Rheum. 1990;33(2):160-172.
8. Mease PJ, Arnold LM, Crofford LJ, et al. Identifying
the clinical domains of fibromyalgia: contributions from
clinician and patient Delphi exercises. Arthritis Rheum.
2008;59(7):952-960.
9. Baetz M, Bowen R. Chronic pain and fatigue: associations
with religion and spirituality. Pain Res Manag.
2008;13(5):383-388.
10. Moreira-Almeida A, Koenig HG. Religiousness and
spirituality in fibromyalgia and chronic pain patients.
Curr Pain Headache Rep. 2008;12(5):327-332.
LEARNING OBJECTIVES
Upon completion of this activity, participants will be able to:
• Describe the pathophysiology of fibromyalgia (FM) and
how it influences treatment.
• Discuss pharmacologic approaches to the management of
FM, including existing and emerging therapies.
• Identify the role of dietary supplements, lifestyle, and
complementary therapies in the management FM.
• Explain how nonpharmacologic therapies can enhance
patient outcomes.
• Design a treatment program for the patient with FM that
includes integrative approaches.
ACCREDITATION STATEMENT
The American Academy of Pain Management is accredited by
the Accreditation Council for Continuing Medical Education
to provide continuing medical education for physicians.
CREDIT DESIGNATION
The American Academy of Pain Management designates this
educational activity for a maximum of 1 AMA PRA Category
1 Credit™. Physicians should only claim credit commensurate
with the extent of their participation in the activity.
FACULTY INFORMATION AND DISCLOSURES
As an accredited sponsor of continuing medical education,
the American Academy of Pain Management must ensure fair
balance, independence, objectivity, and scientific rigor in all
of its sponsored educational activities. All individuals in the
position to control content, including faculty, writers, editors,
reviewers, and activity planners, must disclose to the activity
audience any significant financial interest or other relationship
with manufacturer(s) of any commercial product(s) and/or
provider(s) of commercial services held within the last 12
months. The Academy has policies and procedures in place in
the event that a conflict of interest (COI) is identified.
LESLEY M. ARNOLD, MD, is Director of Women’s Health
Research and Professor in the Department of Psychiatry at the
University of Cincinnati College of Medicine in Cincinnati,
Ohio. Dr. Arnold’s research focuses primarily on fibromyalgia,
women’s health, and mood and anxiety disorders. She has
published more than 70 articles on these subjects and is
on the editorial board for Pain Medicine News. Dr. Arnold
has also received NIH grant support for family and genetic
studies of fibromyalgia and fibromyalgia clinical trials in
adults and children. She has participated on the NIH Chronic
Fatigue/Fibromyalgia Special Emphasis panel since 2000, and
frequently lectures nationally and internationally.
Dr. Arnold reports that she receives research support from Eli
Lilly and Company, Pfizer Inc., Cypress Bioscience, Inc., Wyeth,
Boehringer Ingelheim, Allergan, Inc., and Forest Laboratories,
Inc.; receives consulting fees from Eli Lilly and Company, Pfizer
Inc., Cypress Bioscience, Inc., Wyeth, Boehringer Ingelheim,
Forest Laboratories, Inc., Allergan, Inc., Takeda Pharmaceutical
Company Limited, UCB, Theravance, Inc., AstraZeneca, and
sanofi-aventis; and is on the speaker’s bureaus of Eli Lilly and
Company, Pfizer Inc., and Forest Laboratories, Inc.
MELINDA RING, MD, is the Medical Director of the
Northwestern Memorial Physicians Group Center for Integrative
Medicine and Wellness and Assistant Clinical Professor of
Medicine at Northwestern University, Feinberg School of
Medicine in Chicago, Illinois. Dr. Ring received her medical
degree and internal medicine training from the University of
Chicago, and completed the University of Arizona Integrative
Medicine Fellowship. She has published numerous articles
and chapters, and has co-directed an integrative medicine
conference. Dr. Ring is currently the Northwestern delegate to
the Consortium of Academic Medical Centers for Integrative
Medicine. She also serves on the Advisory Boards for the
Children’s Memorial Hospital Integrative Medicine Initiative
and the Pacific College of Oriental Medicine.
Dr. Ring reports that she has nothing to disclose.
The writer (Christine Rhodes), reviewer, activity planners
(Debra Nelson-Hogan and Katie Arseniadis), and other staff of
the American Academy of Pain Management in a position to
control content report that they have nothing to disclose.
INSTRUCTIONS
To receive credit for this activity, you must review the full
content of the program and successfully complete the posttest,
answering 7 of the 10 questions correctly. It is estimated that
this activity will take approximately 1 hour to complete.
The American Academy of Pain Management respects and
appreciates your opinions. To assist us in evaluating the
effectiveness of this activity and to help us determine future
educational offerings, please complete the evaluation questions.
FEE
There is no charge for members of the American Academy of
Pain Management.
COMMERCIAL SUPPORT
This activity is supported by an educational grant from Lilly
USA, LLC. For further information concerning Lilly grant
funding, visit www.lillygrantoffice.com. This activity is
equally supported by an educational grant from Pfizer Inc.
DISCLOSURE STATEMENT
The opinions expressed are those of the authors and may
include the discussion of off-label uses of medications and
do not necessarily represent the opinions of the American
Academy of Pain Management.
3
 Part 1: Clinical Characteristics and
Pathophysiology of Fibromyalgia
Lesley M. Arnold, MD
Professor of Psychiatry
Director, Women’s Health Research Program
University of Cincinnati College of Medicine
Cincinnati, Ohio

DIAGNOSIS AND CLINICAL PRESENTATION
Fibromyalgia (FM) is a common, chronic pain disorder
that affects approximately 2% of the United States general
population, predominately women (1,2). FM is defined
by the American College of Rheumatology (ACR) 1990
classification criteria as chronic, widespread pain occurring
in combination with pain on palpation at 11 or more of 18
specific tender point sites (1). Although the ACR criteria for
FM require tenderness in 11 of 18 distinct areas, FM patients
characteristically display enhanced sensitivity to mechanical
pressure throughout the body (3).
problems, sleep disturbance, stiffness, depression or anxiety,
tenderness, and impairment in physical, social, or occupational
function and quality of life (QOL) (4-6).
Medical and psychiatric comorbid disorders are common
in patients with FM. In a study of a US health insurance
database, FM patients were more likely than others to have
painful neuropathies, circulatory disorders, depression,
diabetes, sleep disorders, gastroesophageal reflux disease
(GERD), anxiety, and irritable bowel syndrome (IBS) (7).
Other studies have found high lifetime rates of mood and
anxiety disorders in patients with FM (8).

In addition to chronic widespread pain and tenderness, which CASE STUDY

are included in the ACR classification criteria, a mix of other
symptoms commonly occurs in FM patients. The domains of Susan B., a 54-year-old woman who is married with 2 adult
FM consistently rated by patients and clinicians as the most children, sought treatment for diffuse pain and stiffness that
common and troublesome include pain, fatigue, cognitive began about 2 years ago, along with insomnia, which leaves
her tired for a good part of the day. Over the
last year, she has had increasing difficulty
Table 1. Medical and Psychiatric Comorbidity in Fibromyalgia maintaining her usual level of activity, including
housekeeping and walking for exercise. She also
Medical disorder Prevalence Psychiatric disorder Lifetime prevalence
reports headaches and difficulty concentrating
Chronic fatigue syndrome 21-80% Major mood disorder 73.1% at work, which is creating stress with her
 Major depressive disorder 62% employer. She rates her pain as 7 on the 0-10
Irritable bowel syndrome 32-80%
numeric rating scale (0=no pain and 10=worst
 Bipolar disorder 11.1%
Temporomandibular 75% possible pain) and describes it as a dull aching
disorder feeling all over her body. Her family history
Anxiety disorder 55.6%
Tension and migraine 10-80% includes a sister who suffered from chronic
 Panic disorder 28.7%
headache pain and depression. Upon examination, 14
Multiple chemical 33-35%  Posttraumatic stress 21.3% out of the 18 tender points associated with
sensitivities disorder
FM are painful on palpation. There are no
Interstitial cystitis 13-21%  Social phobia 19.4% other physical exam findings. Laboratory
 Obsessive compulsive 6.5% studies to rule out thyroid disease, as well as
Chronic pelvic pain 18%
disorder rheumatologic and autoimmune disorders, are
all within normal limits. The patient’s history
Adapted from: Aaron LA, Buchwald D. Chronic diffuse musculoskeletal pain, fibromyalgia and of 2 years of widespread pain, with no other
co-morbid unexplained clinical conditions. Best Pract Res Clin Rheumatol. 2003;17(4):563-574; Arnold
LM, Hudson JI, Keck PE Jr, Auchenbach MB, Javares KN, Hess EV. Comorbidity of fibromyalgia and
manifestation of signs or symptoms that might
psychiatric disorders. J Clin Psychiatry. 2006;67(8):1219-1225. suggest a different rheumatologic disorder, is
suggestive of FM.

4
Susan presents with several symptoms and
Table 2. Mechanistic Classification of Chronic Pain
a history that point to a diagnosis of FM,
Disorders: Mixed Features in Some Patients
but in other patients, the presence of mood
disorders or other conditions that cause Peripheral
(nociceptive)
chronic pain may complicate diagnosis and
treatment (8,9) (Table 1).
 Inflammation or
mechanical damage
PATHOPHYSIOLOGY
 Classic examples
Familial Factors  Osteoarthritis
 Rheumatoid arthritis
A large controlled study showed that FM
aggregates strongly in families (10). In this
study, the odds ratio (OR) measuring the
odds of FM in a first-degree relative of a
patient with FM versus the odds of FM in a
relative of a patient with the control condition,
rheumatoid arthritis (RA), was 8.5. In addition, Adapted from: Clauw DJ. Fibromyalgia: an overview. Am J Med. 2009;122(suppl 12):S3-S13.
both tender point count and total myalgic
scores were strongly associated with FM in
families, suggesting that inherited factors may
be involved in pain sensitivity. FM coaggregated in families
with major mood disorder (10), and also coaggregated with
mood disorder, anxiety disorder, eating disorders, IBS, and
migraine, taken collectively (11). These results suggest that
FM may share common physiologic abnormalities with some
psychiatric and medical disorders.
Stress Response Systems
Patients with FM often report the onset of their symptoms after
a period of substantial physical or emotional stress. Chronic
stress might promote disturbances in the stress response systems
that could lead to the development of FM. Patients with FM
have been found to have abnormalities in the autonomic nervous
system and the hypothalamic-pituitary-adrenal (HPA) axis (12).
Some studies suggest that there is mild-to-moderate reduction
in the activities of the HPA axis in patients with FM (13-16).
For example, FM has been associated with decreased secretion
of hypothalamic corticotropin-releasing hormone (CRH), an
impaired ability to activate the hypothalamic CRH-pituitary
adrenocorticotropic hormone (ACTH) axis in response to stress,
and a decreased cortisol response to stress (15,17-19). However,
other evidence suggests that FM is associated with hyperactivity
of CRH neurons, including studies showing elevated cortisol
levels associated with a flattened diurnal pattern (20) and
elevation of cortisol in the late evening quiescent period,
consistent with a loss of HPA axis resiliency (21). In recent
studies, pain, but not fatigue, was strongly associated with
cerebrospinal fluid (CSF) CRH concentration (22) and elevated
cortisol levels (23), suggesting that HPA axis hyperactivity is
linked specifically to FM pain. Women with FM who had a
history of physical or sexual abuse had significantly lower levels
of CSF CRH than those without abuse histories (22). Therefore,
Central
Neuropathic (nonnociceptive)
 Damage or entrapment  Central disturbance in
of peripheral nerves pain processing
 Classic examples  Classic examples
 Diabetic peripheral  Fibromyalgia
neuropathic pain  Irritable bowel/bladder
 Post-herpetic neuralgia  Headache
 Idiopathic low
back pain
 Temporomandibular
disorder
 Chronic pelvic pain
the inconsistencies of HPA findings in FM may be related
to several factors, including the presence of comorbidities,
symptom variability, duration of FM, and the confounding
influence of abuse and other stressors.
Studies of the autonomic nervous system in FM patients
consistently show impairment in the sympathetic response
to stressors (24,25). Patients with FM have reduced
vasoconstrictor responses to acoustic and cold stressors,
reduced heart rate response to exercise, and reduced
epinephrine response to hypoglycemia stress (13,15,26,27).
There is also evidence that FM patients have an altered
sympathetic response to upright posture and tilt table testing
(28-30) and abnormalities in heart rate variability. These
findings suggest that FM patients are characterized by a
sympathetic nervous system that is persistently hyperactive
but is hyporeactive to stress (31). This is consistent with an
already overloaded nervous system that is unable to respond
to additional stressors. The decreased sympathetic response
to exercise and the evidence for a paradoxical fall, rather
than rise, in cortisol levels after exercise (27) might explain
postexertional pain and fatigue in some patients with FM (24).
Central Nervous System Pain Processing
With any pain condition, there is a great deal of heterogeneity
with respect to the underlying cause. Patients with pain can
have varying degrees of peripheral nociceptive and central
nonnociceptive factors contributing to their pain (32). Table
2 provides a contemporary view of chronic pain as that
originating from 3 different sources: peripheral nociceptive
input, such as damage or inflammation of tissues; nerve
damage or dysfunction, or neuropathic pain (NP); and
“central” spinal and supraspinal mechanisms.
5
 Historically, there has been a tendency to consign “diseases”
to different pain categories. However, it appears that for nearly
any chronic pain state, even one characterized by peripheral
nociceptive input, central neuronal factors also contribute to the
underlying cause. These central factors play a prominent role
in determining individual differences in pain sensitivity, and,
thereby, clinical outcomes, and can be thought of as a volume
control or gain setting on the peripheral nociceptive input. The
differential diagnosis of chronic pain includes identifying the
degree to which these factors are present in a given individual
so that the appropriate treatments can be administered (32).
Further evidence for a central influence on pain processing
comes from the finding that 30% to 40% of individuals with
distinct radiographic signs of osteoarthritis (OA) do not have
pain, while conversely only about 10% of individuals with
moderate-to-severe knee pain have normal radiographs (33).
Furthermore, in chronic low back pain (CLBP), there is very
little relationship between findings on back imaging studies
and patients’ experience of pain. This discrepancy can be
appreciated by the results of a study of CLBP patients in
which pain sensitivity at the thumb was a greater predictor
of pain and functional status than was the radiographic or
MRI image (34). These findings suggest that chronic pain
is a complex experience with central disturbances in pain
processing playing a significant role. Thus, larger subsets
of individuals with CLBP, OA, or RA may have evidence
of peripheral nociceptive input, and more with FM have
prominent central factors, but it is likely that no chronic
pain state is solely due to any one of these mechanisms.
Central Augmentation of Pain in FM
Neuroimaging studies provide evidence for central
augmentation of pain sensitivity in FM patients. In a study using
functional magnetic resonance imaging (fMRI), the pattern of
cerebral activation during the application of painful pressure
was assessed in FM patients compared with controls (35). There
was an overlap between activations in patients and activations
evoked by greater stimulus pressures in controls. In addition,
application of mild pressure to both patients and controls
resulted in a greater number of activated regions in patients.
Both of these findings provide evidence that pain sensitivity
is augmented in FM. fMRI studies of CLBP patients showed
similar patterns of neuronal activation in pain-related cortical
areas as in FM, demonstrating the occurrence of augmented
central pain processing in other chronic pain disorders (36).
Chronic pain is associated with increased excitation and
decreased inhibition of ascending pain pathways. In one
possible mechanism of abnormal pain processing, the pain
transmission neurons become sensitized in response to intense
or prolonged exposure to painful stimuli and augment the
transmission of pain signals into the brain (3). Central pain
6
sensitization results from plasticity of neuronal synapses
following past pain experiences at the level of the dorsal horn
so that input that would normally be transmitted as pressure or
movement becomes transmitted as pain. Increased sensitivity to
pain may be manifested by changes in response to evoked pain,
such as generalized hyperalgesia (increased response to painful
stimuli) or allodynia (the experience of pain from normally
nonnoxious stimuli) (37).
Figure 1 shows how central pain sensitization might develop
(38). Intense or prolonged impulses from afferents depolarize
dorsal horn neurons. An influx of extracellular calcium into
the neurons results in an exaggerated release of pronociceptive
transmitters or neuromodulators, substance P and glutamate,
leading to neuronal hyperexcitability. The amplified pain signal
is sent to the brain. Consistent evidence regarding elevated
levels of substance P and limited data regarding elevated
glutamate metabolites in the CSF of FM patients provide
indirect evidence of the role of central pain sensitization (39,40).
Figure 1. Model of Central Pain Sensitization
The mechanoreceptors, or A-beta fiber system, provide sensory proprioceptive
input, which is mostly relayed to the dorsal columns. But the A-beta fibers also
connect with wide-dynamic range projection neurons. When these neurons are
sensitized, the mechanoreceptor information “accesses” the pain system and
translates normally innocuous cutaneous and musculoskeletal sensations into
painful tenderness and movement sensations. It is also thought that mechano-
receptor information coming from deep tissues such as paraspinal structures is
referred into broader regional patterns of pain and tenderness.
From: Littlejohn GO. Balanced treatments for fibromyalgia. Arthritis Rheum.
2004;50(9):2725-2729. Used with permission from Arthritis & Rheumatism.
There is also evidence for increased levels of nerve growth
factor (NGF) and brain-derived neurotrophic factor (BDNF)
in the CSF of FM patients. NGF might indirectly enhance
glutamatergic transmission via BDNF, which could account
for the sustained central sensitization in FM (40). Changes
in glutamate levels in the insula of the brain were associated
with changes in multiple pain domains in patients with
FM, supporting the role of glutamate as a major excitatory
neurotransmitter involved in pain transmission and in FM
(41). Medications that decrease the release of pronociceptive
transmitters, like substance P and glutamate, can turn down
this process and reduce pain (38,42). The analgesic capacity
of pregabalin and gabapentin, both of which are alpha-2-delta
ligands that are currently used in the treatment of FM, is
hypothetically linked to reduction in the release of glutamate
and substance P (43).
Studies also indicate that another possible mechanism involved
in the painful symptoms of FM involves aberrations in the
descending pain inhibitory pathways (44,45). The descending
pain modulatory pathway involves most of the nervous
system, beginning at the cortical level going down through
the midbrain and then ultimately into the dorsal horn of the
spinal cord (46). Decreased levels of dopamine, serotonin,
and norepinephrine metabolites in the CSF of FM patients
suggest that deficiencies in the central nervous system (CNS)
activity of these bioamines may play a role by disrupting the
normal function of this inhibition system (44,45). Mesolimbic,
mesocortical, nigrostriatal dopamine pathways are involved
in the inhibition of nociception, primarily its affective
component. Research using positron emission tomography has
shown that FM patients have an abnormal dopamine response
to pain compared with control subjects (47). Dopamine may
be involved in the modulation of descending control, although
the precise mechanism remains to be elucidated (45).
Medications that increase the availability of norepinephrine,
serotonin, or dopamine may promote pain inhibition centrally.
A preliminary study suggested that dopamine agonists may be
beneficial for FM, but more study is needed to clarify the role
of dopamine in treatment (48).
Serotonin is a mixed neurotransmitter, and depending on
its receptor, can have pronociceptive and antinociceptive
effects. Thus, medications that result in broad enhancement
of serotonin, such as selective serotonin reuptake inhibitors
(SSRIs), produce a weak antinociceptive effect. The
SSRIs fluoxetine, paroxetine, and citalopram have been
studied in FM, with inconsistent results (49). In addition
to serotonin’s role in pain modulation, central serotonergic
neurotransmission has been postulated to mediate a
qualitative abnormality of sleep in patients with FM (50).
This sleep abnormality consists of inappropriate intrusion
of alpha waves (normally seen during wakefulness or REM
sleep) into deep sleep (characterized by delta waves) (51),
and is thought to contribute to the musculoskeletal pain and
fatigue of FM (50). Although this sleep abnormality is not
specific for FM and the underlying cause of sleep disturbance
in FM is not completely understood, management of sleep
is an important component of overall treatment. Notably,
self-reported restorative sleep was associated with resolution
of chronic widespread pain in a recent population-based
prospective study (52), providing support for the important
role of sleep quality in pain disorders.
Animal studies have shown that enhancement of
norepinephrine alone produces a more pronounced
antinociceptive effect than that with serotonin; however, the
dual reuptake inhibition of serotonin and norepinephrine
produces the most consistent pain effect (53). Tricyclic
compounds, such as amitriptyline and cyclobenzaprine,
enhance serotonin and norepinephrine in the descending
pain pathways and have been shown to reduce pain (54).
However, because of their affinity for multiple receptors,
they are associated with adverse effects (AEs) related to
their anticholinergic, antiadrenergic, antihistaminergic,
and quinidine-like effects, which limits their use in many
patients. Duloxetine and milnacipran are selective serotonin
and norepinephrine reuptake inhibitors (SNRIs) that are FDA
approved for the management of FM (55).
Other chronic central pain disorders, such as chronic headache,
IBS, temporomandibular disorders (TMD), and CLBP, also
respond to medications that enhance neurotransmission of
serotonin and norepinephrine, supporting the concept of a central
pain mechanism affecting overall pain sensitivity (56-59). In
addition, migraine and NP respond to the alpha-2-delta ligands
(60-62). Both gabapentin and pregabalin are FDA approved
for the treatment of postherpetic neuralgia, and pregabalin is
approved for the treatment of diabetic peripheral NP.
SUMMARY
There is emerging evidence of the possible familial and
environmental factors that could be involved in the etiology
of FM. Environmental stressors and genetic vulnerability
could act alone or together to initiate a series of biological
events in individuals that eventually leads to the development
of FM. Recent studies also demonstrate augmentation of
central pain processing in FM. It appears that disturbances in
the stress response system may play a key role in the process
that leads to FM. These same CNS changes could also be
involved in the development of associated symptoms and other
comorbid conditions. FM is heterogeneous in its presentation
and probably in underlying pathophysiology, making
individualized treatment essential.
In the next section of this monograph, Dr. Ring describes the
current pharmacologic and nonpharmacologic treatments that
are used in FM.
7
 References
1. Wolfe F, Smythe HA, Yunus MB, et al. The American
College of Rheumatology 1990 Criteria for the
Classification of Fibromyalgia. Report of the Multicenter
Criteria Committee. Arthritis Rheum. 1990;33(2):160-172.
2. Wolfe F, Ross K, Anderson J, Russell IJ, Hebert L. The
prevalence and characteristics of fibromyalgia in the
general population. Arthritis Rheum. 1995;38(1):19-28.
3. Baranauskas G, Nistri A. Sensitization of pain pathways
in the spinal cord: cellular mechanisms. Prog Neurobiol.
1998;54(3):349–365.
4. Mease PJ, Clauw DJ, Arnold LM, et al. Fibromyalgia
syndrome. J Rheumatol. 2005;32(11):2270-2277.
5. Arnold LM, Crofford LJ, Mease PJ, et al. Patient
perspectives on the impact of FM. Patient Educ Couns.
2008;73(1):114-120.
6. Goldenberg DL. Diagnosis and differential diagnosis of
fibromyalgia. Am J Med. 2009;122(suppl 12):S14-S21.
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acteristics and healthcare costs of patients with fibromyal-
gia syndrome. Int J Clin Pract. 2007;61(9):1498-1508.
8. Arnold LM, Hudson JI, Keck PE Jr, Auchenbach MB, Java-
res KN, Hess EV. Comorbidity of fibromyalgia and psychia-
tric disorders. J Clin Psychiatry. 2006;67(8):1219-1225.
9. Aaron LA, Buchwald D. Chronic diffuse musculoskeletal
pain, fibromyalgia and co-morbid unexplained
clinical conditions. Best Pract Res Clin Rheumatol.
2003;17(4):563-574.
10. Arnold LM, Hudson JI, Hess EV, et al. Family study of
fibromyalgia. Arthritis Rheum. 2004;50(3):944-952.
11. Hudson JI, Arnold LM, Keck PE Jr, Auchenbach MB,
Pope HG Jr. Family study of fibromyalgia and affective
spectrum disorder. Biol Psychiatry. 2004;56(11):884-891.
12. Pillemer SR, Bradley LA, Crofford LJ, Moldofsky H,
Chrousos GP. The neuroscience and endocrinology of
fibromyalgia. Arthritis Rheum. 1997;40(11):1928-1939.
13. Adler GK, Kinsley BT, Hurwitz S, Mossey CJ, Goldenberg
DL. Reduced hypothalamic-pituitary and sympathoadrenal
responses to hypoglycemia in women with fibromyalgia
syndrome. Am J Med. 1999;106(5):534-543.
14. Torpy DJ, Papanicolaou DA, Lotsikas AJ, Wilder RL,
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30. Raj SR, Brouillard D, Simpson CS, et al. Dysautonomia
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9
 Part 2: Treatment of Fibromyalgia
Melinda Ring, MD
Medical Director
Northwestern Memorial Physicians Group Center for Integrative Medicine and Wellness
Assistant Clinical Professor of Medicine
Northwestern University, Feinberg School of Medicine
Chicago, Illinois
The treatment goal of fibromyalgia (FM) is to develop an
individualized approach that addresses the severity of the
patient’s pain, the presence of comorbidities, and the degree
of the patient’s functional impairment. In most cases, effective
management involves a variety of treatments, including
neuromodulatory medications and nonpharmacologic measures,
such as exercise and cognitive behavioral therapy (CBT).
Increases in our understanding of FM pathophysiology have
resulted in new pharmacologic agents that are effective and
safe in many patients. Yet, because of the heterogeneous nature
of FM, these medications may only be effective for some
patients and sometimes only to a partial extent, especially if
used as monotherapy (1). Thus, a patient on pharmacotherapy
may experience only a partial reduction in pain or other
symptoms and seek additional treatment solutions for greater
relief. In an integrative practice, education and pharmacologic
therapies, together with lifestyle approaches, are the
foundation of FM treatment. A core principle of integrative
medicine is its orientation toward patient-centered care, in
which the personal needs and beliefs of the patient are given
priority; the clinician embarks on a journey with the patient,
Table 1. Integrative Approach to Fibromyalgia
Education
Pharmacologic and biologic therapies
 Medications
 Supplements
Lifestyle approaches
 Diet
 Physical activity
 Sleep
Complementary therapies
 Acupuncture
 Bodywork
 Energy medicine
Mind/body
 Relaxation therapy
 Psychotherapy/cognitive behavioral therapy
 Spirituality
10
selecting from the variety of treatment options available.
Successful treatment depends on matching the right therapy to
the appropriate patient (Table 1).
As many as 90% of FM patients use at least one
nonpharmacologic treatment (2). Even clinicians who do
not use these treatments in their own practice must become
knowledgeable about their effectiveness and safety in order to
provide individualized counseling to patients.
PHARMACOLOGIC TREATMENT
Pharmacologic treatments for FM address either the increased
excitation or decreased inhibition of ascending pain pathways.
Medications that reduce the release of pronociceptive
transmitters or neuromodulators substance P and glutamate,
such as the alpha-2-delta ligands pregabalin and gabapentin,
are thought to reduce pain facilitatory mechanisms, or
ascending pain signals to the brain. Medications that enhance
serotonin and norepinephrine by blocking the reuptake of
these neurotransmitters seem to enhance the pain inhibitory
effects in the descending inhibitory pathways.
Table 2 provides an overview of medications that are
currently used in the treatment of FM. Several medications
that have effects on serotonin and norepinephrine have been
studied in FM. Amitriptyline and cyclobenzaprine have a
moderate overall effect on FM, with the largest effect found
in improving sleep quality. These medications continue to
be used, usually at night because of their sedative properties,
but some patients experience problems with their safety and
tolerability (3).
The alpha-2-delta ligands are anticonvulsant agents that reduce
neuronal hyperexcitability. By binding to the alpha-2-delta
subunit of voltage-gated calcium channels in neurons, they
reduce the influx of calcium into the neuron and inhibit the
release of substance P and glutamate. Pregabalin is approved
for the management of FM in doses of 300 to 450 mg/day.
Gabapentin has been studied in FM at doses ranging from
1200 to 2400 mg/day, but it is currently not approved for this
indication. Clinical trials of both agents have shown efficacy
in reducing pain and improving sleep, as well as improving
global assessment, function, and health-related QOL (4-8).
The most commonly reported adverse effects (AEs) were
mild-to-moderate, dose-related dizziness and somnolence.
SNRIs have been shown to be effective as antinociceptive
agents in chronic pain conditions and lack many of the
safety concerns of tricyclic antidepressants. Their efficacy
is thought to be due to their ability to increase serotonin and
norepinephrine-mediated neurotransmission in the descending
pain inhibitory pathways in the brain and spinal cord. By
doing so, they may correct a functional deficit in serotonin and
norepinephrine in these pathways that occurs in chronic pain.
Agents with dual serotonin and norepinephrine activity have
more consistent benefits in relief of persistent pain than those
with serotonergic activity alone (9,10).
Duloxetine is approved by the FDA for the management of
FM. Results of clinical trials demonstrated that duloxetine
at doses of 60 mg (FDA-approved dose) and 120 mg/day
significantly reduced pain and improved global assessment,
function, and health-related QOL (11-14). Notably, duloxetine
was effective in patients with or without current major
depression. Thus, its effects on pain reduction appear to
be independent of effects on mood (15). Patients reported
significantly higher incidences of nausea, dry mouth,
constipation, decreased appetite, and anorexia compared
with placebo, but no safety concerns were identified.
Milnacipran is the most recent SNRI approved for the
management of FM. Clinical trials showed that patients on
doses of 50 mg and 100 mg bid were significantly more
likely than those on placebo to have a positive response to
treatment, including a reduction in pain, and improvements
in global assessment, function, health-related QOL,
fatigue, and perceived cognitive impairment (16-19).
The most frequently reported AEs were nausea, headache,
and constipation.
ADDITIONAL PHARMACOLOGIC APPROACHES
Other approaches to the treatment of FM and its concomitant
symptoms have been studied with mixed results (20). For
example, the nonbenzodiazepine sedatives zolpidem and
zopiclone have been studied for their ability to improve sleep
(21-23). Results in FM patients have shown improvements in
sleep, but not pain. The use of opioids in FM is limited by lack
of efficacy data, as well as their abuse potential and ability to
induce hyperalgesia (20). Studies of tramadol, a weak mu-opiate
receptor agonist with dual serotonin and norepinephrine reuptake
inhibition activity, have demonstrated efficacy, particularly when
taken in combination with acetaminophen (24-26).
Table 2. Pharmacologic Treatment of Fibromyalgia
Alpha-2-delta ligands
 Pregabalin (approved by the FDA in 2007
for the management of FM)1
 Gabapentin*
Serotonin/norepinephrine reuptake inhibitors
 Tricyclic antidepressants and analogues
(eg, amitriptyline, cyclobenzaprine)*
 Duloxetine (approved by the FDA in 2008
for the management of FM)1
 Milnacipran (approved by the FDA in 2009
for the management of FM)1
*This information concerns a use that has not been approved by the
US Food and Drug Administration
1
US Food and Drug Administration. Available at: http://www.
accessdata.fda.gov/Scripts/cder/DrugsatFDA.
Accessed March 5, 2010.
Clinical trials of other pharmacologic therapies have
been conducted based on several proposed mechanisms
of analgesia and have produced mixed results. These
medications include the 5-HT3 antagonist tropisetron (27,28),
the N-methyl-D-aspartate (NMDA) receptor antagonist
dextromethorphan (29,30), the dopamine D2/D3 receptor
agonist pramipexole (31), and the anti-inflammatory
medications prednisone (32) and ibuprofen (33).
Nonsteroidal anti-inflammatory drugs have been shown to
provide the greatest benefit in patients who have a comorbid
inflammatory condition, such as osteoarthritis (OA) (20).
Sodium oxybate, a sedative hypnotic used for narcolepsy,
is the sodium salt form of gamma-hydroxybutyrate, an
endogenous neurotransmitter and metabolite of gamma-
amino-butyric acid (GABA). Results of phase 3 trials have
shown a decrease in pain and fatigue, and improvement in
function, patients’ global impression of change, and sleep
quality (34,35).
CASE STUDY (CONTINUED)
Because of Susan’s moderate-to-severe pain and prominent
insomnia, a trial of an alpha-2-delta medication is prescribed,
and she is given several educational brochures on FM.
Several weeks later, Susan reports that her pain and
insomnia are somewhat relieved, but she still has difficulty
managing her everyday tasks and often feels as if she cannot
cope with her condition. Because she has experienced
some improvement already on the alpha-2-delta agent, an
increased dose is prescribed and a program of walking, with
gradual increases in distance, is recommended, because she
enjoyed it in the past.
11
 Although Susan expresses doubt that she can find the energy to
exercise, she agrees to try it. If Susan continues to complain about
fatigue, a trial of an SNRI may be the next step in her treatment.
NONPHARMACOLOGIC THERAPIES
The medications discussed above have been the agents most
extensively studied for the treatment of FM. New medications
continue to be investigated and will expand patients’ options.
For most patients, however, FM treatment involves both
pharmacologic and nonpharmacologic approaches. Among
nonpharmacologic options, the evidence for education,
exercise, and CBT is most consistent. Other therapies that
focus on dietary supplementation and nontraditional healing
are also frequently used, but the rigorous evidence for their
effectiveness is often lacking.
Education
Education is an important component of treatment with
measurable benefits when combined with other approaches. A
recent study showed that self-management education enhanced
the benefits of a supervised exercise program that included
strength, aerobic, and flexibility training in patients who were
also receiving medication (36). In this program, the addition
of the Arthritis Foundation’s FM self-management course led
to a reduction of the impact of FM on physical, social, and
emotional function over a period of 6 months.
Other research has shown that the combination of education
and a social support group can be more effective than a social
support group alone in combating helplessness (37). However,
the attendance rates for these groups are often low. Research
on the benefits of education has shown that an online arthritis
self-management program was effective in improving health
status measures, such as pain and fatigue, and provided a
viable alternative to small-group self-management programs
(38). Patients with rheumatoid arthritis (RA), OA, and FM
in this study participated in an interactive, online program
for 1 to 2 hours, 3 times per week, for 6 weeks. In addition,
they were required to read about their condition, develop an
action plan, and perform self-assessments. One year later, FM
patients still showed the benefits of the intervention, but not
as much as arthritis patients. These programs have the greatest
potential for use as an adjunct to one-on-one interaction with a
healthcare provider.
Exercise
Physical activity does not significantly reduce pain for most
FM patients, but it improves other aspects of overall patient
care. Patients with chronic pain often become sedentary, which
leads to deconditioning and contributes to other symptoms.
Exercise can reduce the impact of deconditioning, but the
12
exact mechanism by which exercise improves FM is still
unknown. Research has also shown that aerobic training
at a moderate intensity improves patients’ overall sense of
well-being and physical function. In addition, strength and
flexibility training may reduce pain and tenderness as well as
improve mood, function, and overall well-being (36,39).
It is important to introduce exercise at a level below the
patient’s fitness level and increase as tolerated. Supervised
group exercise seems most effective in improving compliance
and participation. Aerobic warm water exercise classes may be
helpful, and can serve as a precursor to a land-based program
of low-impact exercise.
Cognitive Behavioral Therapy
CBT can help patients with FM reduce symptoms, increase
their ability to cope with the disease, and identify and limit
maladaptive illness behavior (40). For example, certain
cognitions have been identified that seem to perpetuate
patients’ pain. Catastrophizing, or the tendency to rate
everything in an overly negative or overwhelming way,
can be addressed successfully with CBT. Patients who are
said to have an external locus of control, meaning that they
externalize their problems and tend to feel a lack of control
over their symptoms, seem to have more problems with
pain. CBT can help such patients develop more of a sense of
internal control, and this can result in lasting improvement in
physical function (40).
One study of 71 FM patients evaluated a 10-week program
comprised of 90-minute group sessions of education,
relaxation training, goal setting, and activity pacing, with the
involvement of a support person to promote coping skills and
program adherence (41). The treatment resulted in significant
reductions in depression, self-reported pain behavior, observed
pain behavior, and pressure pain thresholds, but pain intensity
levels were not reduced.
Originally developed for mood and anxiety disorders, CBT has
been shown to be effective for many chronic diseases, but not
every community has available therapists. Several online and
published self-help approaches to FM are available that teach
patients about basic cognitive behavioral skills and exercises
they can incorporate into their daily lives.
CASE STUDY (CONTINUED)
The next time Susan comes in, she reports that the walking
has been helpful in getting her out of the house and improving
her mood. She feels somewhat stronger and more in control
of her FM. The increase in medication has helped as well,
particularly with her sleep problems, but she still feels pain
and the stress at work is increasing. She says that a friend
has recommended that she try acupuncture to relieve her pain
further, and she wants to discuss it first with you.
You respond by first reinforcing her positive efforts in
making lifestyle changes, and validate the challenges she is
experiencing in her workplace as she learns to manage her
condition. You explain that although the scientific studies
on acupuncture in FM have had mixed results on pain
reduction, it may be beneficial for other symptoms such as
sleep and stress reduction, and suggest a trial of 6 to 8 weekly
acupuncture treatments with a qualified practitioner. You also
mention that 10 to 20 minutes/day of a relaxation technique,
such as meditation, guided imagery, and progressive muscle
relaxation, can be beneficial for her overall well-being.
You also review her lab results, particularly for evidence of
deficiencies such as vitamin D25-OH, RBC, and magnesium.
Appropriate supplements are suggested to help bring these
into their optimal range. You conclude by acknowledging the
improvements she has made on the medication and through
her walking program, and stressing the importance of
continuing these elements of her regimen while you continue
to work together for positive change.
ADDITIONAL NONPHARMACOLOGIC THERAPIES
Several systematic reviews of research on nonpharmacologic
therapies for the treatment of FM have shown that the
randomized controlled trials that have been performed
to date are generally of poor quality (42,43). Often there is
only one study published on a particular therapy, or studies
have different outcomes measures, so they cannot be
combined, and, unlike pharmaceutical trials, there are
usually small enrollments.
Despite these limitations, it is important to consider a
patient’s experience in evaluating the benefits of a particular
therapy. Even if the evidence concludes otherwise, many
nonpharmacologic therapies offer relief to FM patients and
should not be discounted as long as they are used in a safe
and supervised manner.
Dietary supplements
Dietary supplements are a small but integral part of an
integrative treatment plan, but few studies have examined
their use in FM. The supplements used in FM are often based
on differing theories of the underlying pathophysiology (see
below). When treating FM patients, incorporating supplements
targeting multiple systems often yields the most benefit. As
many FM patients have some degree of chemical sensitivity, it
is wise to add supplements in a step-wise fashion to minimize
AEs. Most supplements should be used for a minimum of 3
months before declaring a lack of response. It is important
to stop any supplements that are not helping, as the patient
may accumulate large numbers of pills with the potential for
medication-supplement interactions.
Mitochondrial dysfunction. A study by Teitelbaum and col-
leagues examined the effectiveness of supplementation with
D-ribose, a naturally-occurring carbohydrate, on increasing
cellular energy synthesis (44). This research is based on the
theory that there is mitochondrial dysfunction in FM, which
leads to muscle fatigue. D-ribose (5 g, 3 times/day) was giv-
en to 41 patients, and 66% showed significant improvement
in energy, sleep, mental clarity, pain, and well-being. There
are few AEs associated with D-ribose, and it can be tried in
almost all FM patients.
L-carnitine and propionyl-L-carnitine are supplements also
used to improve mitochondrial energy production. A recent
study using a dose of 1500 mg/day of acetyl L-carnitine
showed improvement in pain, tender points, and depression
after 10 weeks of treatment (45).
Nutrient deficiency. There is evidence that magnesium
deficiency is common in FM (46). Magnesium and
malate, both needed for ATP formation, may be
recommended, although limited data on their effectiveness
are available (47,48).
Myers’ Cocktail is an intravenous micronutrient therapy. An
8-week trial of weekly infusion therapy in 31 patients showed
an improvement in tender points, pain, depression, and QOL,
though the results were not statistically significant (49). Pain
reduction persisted at 3 months but the other improvements
were not maintained.
Neurotransmitter regulation. 5-hydroxytryptophan (5-HTP)
is the precursor compound in the synthesis of serotonin.
Several studies have shown that 5-HTP, given in doses of 50
to 150 mg before bed, can reduce the number of tender points
and improve anxiety, pain, sleep, and fatigue (50-52). In the
1980s, contaminated tryptophan products caused episodes
of eosinophilia-myalgia syndrome, but there have been no
incidents of toxicity with 5-HTP. Since 5-HTP raises serotonin
levels, there is the potential for interaction with some of the
SSRIs and SNRIs used in FM. Patients need to be monitored
for signs of serotonin syndrome.
S-adenosylmethionine (SAMe) has analgesic, anti-
inflammatory, and antidepressant effects and modulates
serotonin and norepinephrine levels (53). In one placebo-
controlled study, 800 mg/day was given to 40 patients for
6 weeks (54). Patients demonstrated statistically significant
improvements in pain, fatigue, and morning stiffness but not
in tender point scores, muscle strength, or mood. A crossover
study with 17 patients showed a reduction in the number of
trigger points and improvement in scores on both the Hamilton
13
 and SAD scales for depression (55). SAMe is often more
expensive than other antidepressant supplements, such as
St. John’s Wort or 5-HTP, but it does have unique analgesic
properties. It can cause gastrointestinal AEs, so it is best
reserved for patients with more than one symptom, such as
FM with a mood component, or OA and depression.
DHEA, an adrenal hormone that serves as a precursor to other
hormones, may be deficient in FM (56), and studies are needed
to show whether hyposecretion of adrenal androgens is a cause
of poor health status in FM. The typical daily dose range of
DHEA is 5 to 15 mg for women and 25 to 100 mg for men.
Levels should be monitored by checking serum DHEA-sulfate
levels before and after beginning treatment.
Circadian disorders. Sleep disturbances, or circadian rhythm
disorders, are common in FM, and may be a consequence of
decreased secretion of melatonin, as well as its precursors
tryptophan and serotonin (57). Preliminary research shows
a beneficial effect of 3 mg of melatonin nightly on pain
and sleep (58), and that melatonin may be a safe alternative
treatment for FM patients.
Homeopathy
Homeopathy is based on the principle that “like cures like,”
that what causes symptoms in a healthy subject can help
cure the same condition in someone who is ill. Homeopathic
medications undergo serial dilution to minimize their AEs.
In one crossover study of 30 FM patients fitting a specific
homeopathic profile, a tincture of poison ivy (Rhus tox) was
given in a dilution of 6C (1:100 repeated 6 times). After one
month of treatment, patients showed a 25% improvement in
tender points, pain, sleep, and overall status (59).
Since homeopathy aims to treat each patient individually
based on his or her symptoms, Bell and colleagues reasoned
that the positive results seen with Rhus tox would work only
in those FM patients who were well matched to the treatment
(60). A trained homeopathic practitioner, on the other hand,
would take a detailed history and individualize the treatment
to the patient’s symptoms. In their trial, 62 patients were
randomized to individually-chosen homeopathic therapy
or a placebo. Homeopathic therapy resulted in significant
improvements in tender point count, pain, and QOL.
Nutrition
Several nutritional practices have been shown to regulate
FM symptoms in small studies. A 3-month study in Finland
assessed the effects of a vegan diet on pain, sleep, and
wellness in FM patients (61). Patients ate fruits, legumes,
seeds, nuts, and vegetables, but were not allowed to eat
animal products, coffee, tea, alcohol, sugar, or salt. Symptoms
14
improved during the 3 months of the diet, but returned to
baseline with resumption of a full diet.
Food sensitivities may contribute to FM symptoms and an
elimination diet can identify those foods which are exacerbating
symptoms such as pain, fatigue, or mood. In an elimination diet,
the most common offending foods, such as sugar, alcohol, dairy
products, wheat, eggs, citrus, soy, chocolate, coffee, and artificial
sweeteners and additives, are removed for at least 3 weeks, then
added back one at a time every 4 days. Even if the elimination
diet proves too challenging for patients to maintain, eliminating
certain additives such as monosodium glutamate (MSG), which
is metabolized into glutamate, and aspartame, which is converted
to aspartate, may at least partially resolve FM symptoms (62).
Acupuncture
Acupuncture is often recommended for FM and is generally
safe when performed by a trained practitioner. However, a
systematic review on the use of acupuncture for FM found
only 5 randomized trials that met the criteria for inclusion
(63). Two of the trials yielded negative results and the 3 using
electroacupuncture were positive. The authors concluded that
the effectiveness of acupuncture in FM was not supported by
the results of rigorous clinical trials. A more recent review of
randomized controlled trials found a positive trend in favor of
acupuncture, but noted that the different study designs made it
difficult to draw conclusions (43).
Yoga and Tai Chi
The benefits of yoga have been studied, and small pilot studies
showed that 9 weekly sessions of relaxing yoga showed improve-
ments in pain and function (64). Tai chi is also being studied and
has been shown to be helpful in RA and other conditions (65).
Massage
Research suggests that gentle massage may lower anxiety
and improve sleep quality in FM. After 5 weeks of massage
therapy, 2 times per week, substance P levels decreased
and patients’ physicians assigned lower disease ratings and
documented fewer tender points (66). Another study using
mechanical deep tissue massage showed an improvement in
tender points, pain intensity, and function after 15 treatments
by a physical therapist (67).
Chiropractic and Osteopathic Manipulation
There have only been a few studies examining the benefits
of chiropractic and osteopathic manipulation, but up to 47%
of FM patients seek chiropractic care (68). Two small trials
showed promising though conflicting results (69). Osteopathic
manipulation also showed improvements in tender point
pain thresholds and activities of daily living, but further
investigation is needed (70).
Balneotherapy
Balneotherapy consists of bathing in hot mineral water and
was traditionally offered in spa settings in Europe and the
Middle East. Three randomized trials showed significant
benefits immediately after the end of treatment and at 6-month
follow-up, including a reduction in pain, tender points, and
depression (71-73).
Energy Healing
Many forms of energy healing are based on the concept
that people have a biofield, a subtle form of energy, and
disturbances or blockages in this field can lead to disease.
A trial of 5 to 7 Qigong treatments in 10 FM patients over a
period of 3 weeks resulted in complete recovery in 2 patients
and improvements in pain, depression, and function in the
remaining patients (74).
Reiki is another biofield energy tradition that originated in
Japan, and involves the gentle laying on of hands on or above
different areas of the body. A randomized controlled trial
that used either direct touch or distance healing from a Reiki
master showed no impact on FM symptoms (75).
Meditation
A 2000 review examined 13 trials that assessed therapies that
can help a patient achieve the relaxation response (76). There
was very strong evidence that meditation helped patients
achieve self-efficacy, moderate evidence for improved QOL,
and inconclusive evidence for pain relief.
MIND-BODY-SPIRIT
Attending to the mind-body-spirit aspect of healing is critical
in integrative pain management. It is important that clinicians
acknowledge patients’ pain, and explaining the underlying
pathophysiology can help patients understand the role of
emotion and stress in their symptoms.
Chronic pain patients often develop new relationships with their
religion and spirituality. Some patients look to a higher power
for comfort and guidance, and their spiritual practice becomes
a positive mechanism for coping and healing. Others view this
higher power as being punitive, punishing them with pain. Some
see their disease as evidence of abandonment when they most
need support. It is important for the clinician to help patients
identify what role spirituality plays in their life, and encourage
them to consider how it can become a positive resource.
A large health survey in Canada examined chronic pain patients’
views on religion and spirituality (77). Results showed that
chronic pain patients who identified positively with their
religion or some practice of spirituality had better psychological
well-being and demonstrated positive coping mechanisms. As
clinicians, it is important to help patients understand the types
of coping mechanisms that may be helpful to them, including
sources of community or social support, like religion, or
practices like meditation that can aid in relaxation.
In conclusion, there are several steps to helping FM patients,
and they can be summarized by the mnemonic ACCEPT:
Acknowledge, Chronic, Challenges, Education, Partnership,
Trust. Acknowledge that their pain is real, and inform them
that it is a Chronic condition with Challenges in treatment
and management. In addition to utilizing pharmacologic and
nonpharmacologic therapies to decrease pain and improve
function, Educating patients, being their Partner, and
developing a Trusting relationship, are all important steps for
clinicians to help their patients in the healing journey.
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18
 Posttest
INSTRUCTIONS: This activity should take approximately 1
hour to complete. The participant should read both the learning
objectives and the monograph, and answer the 10 questions
below by circling the single-letter responses that best answer
the questions. The participant should also answer the evaluation
questions. The completed test should be faxed to (212) 532-
5397 or sent via US mail to the following address:
American Academy of Pain Management
Education Department
1123 Broadway, Suite 613
New York, NY 10010
7. Which of the following statements about aerobic exercise
in the treatment of chronic pain is not true?
a. Exercise significantly reduces pain severity.
b. Exercise significantly improves physical function.
c. Supervised group exercise is preferable.
d. Moderate intensity of aerobic exercise is recommended.
8. Which of the following combined with a supervised exer-
cise program has shown the greatest benefit to patients
in reducing the overall impact of FM over 6 months?
a. the use of alpha-2-delta ligands
b. the Arthritis Foundation’s FM self-management course
c. the use of homeopathy
d. a social support group

9. Preliminary research has shown the beneficial effect of

1. The inconsistencies of hypothalamic-pituitary-adrenal
what nightly dosage of melatonin on pain and sleep in
(HPA) axis findings in FM are a reflection of all of the
FM patients?
following factors except
a. 0.5 mg
a. the presence of comorbidities
b. 3 mg
b. symptom variability
c. 6 mg
c. duration of FM
d. 2 mg
d. the number of tender points affected
10. Which of the following therapies showed significant
2. Impairments in the sympathetic response to stress
benefits to FM patients immediately after the end of
include all of the following except
treatment and at 6-month follow-up?
a. increased vasoconstrictor responses to acoustic and
a. reiki
cold stressors
b. chiropractic manipulation
b. altered sympathetic response to tilt table testing
c. acupuncture
b. reduced heart rate in response to exercise
d. balneotherapy
c. reduced epinephrine response to hypoglycemia stress
EVALUATION QUESTIONS
3. Which of the following has been posited to inhibit
Please evaluate the activity by responding to the following
central pain states?
statements:
a. increasing the release of glutamate
b. increasing the release of substance P 1. The following learning objective was met: Describe the
c. increasing the availability of serotonin pathophysiology of FM and how it influences treatment.
d. decreasing the availability of norepinephrine a. Strongly agree
b. Agree
4. Which of the following statements best characterizes c. Neutral
FM patients? d. Disagree
a. They only have increased pain at the ACR tender point sites. e. Strongly disagree
b. They have augmentation of pain processing.
c. Their pain is due primarily to psychological factors. 2. The following learning objective was met: Discuss
d. They are all women. pharmacologic approaches to the management of FM,
including existing and emerging therapies.
5. An integrative approach to the treatment of the patient a. Strongly agree
with FM includes b. Agree
a. education c. Neutral
b. pharmacologic and biologic therapies d. Disagree
c. mind-body therapies e. Strongly disagree
d. all of the above
3. The following learning objective was met: Identify
6. Which of the following is true regarding the the role of dietary supplements, lifestyle, and
treatment of FM? complementary therapies in the management FM.
a. Cognitive behavioral therapy should be avoided. a. Strongly agree
b. Exercise should be avoided. b. Agree
c. It should address all sources of pain and c. Neutral
comorbid symptoms. d. Disagree
d. It should focus on the tender point sites. e. Strongly disagree
19
4. The following learning objective was met: Explain 9. I plan to make changes in my clinical practice as a result
how nonpharmacologic therapies can enhance patient of this activity.
outcomes. a. Strongly agree
a. Strongly agree b. Agree
b. Agree c. Neutral
c. Neutral d. Disagree
d. Disagree e. Strongly disagree
e. Strongly disagree
If you plan to make changes, what will you do differently?
5. The following learning objective was met: Design a
treatment program for the patient with FM that includes
integrative approaches.
a. Strongly agree
b. Agree
c. Neutral
d. Disagree How will you implement these changes?
e. Strongly disagree

6.The activity was fair balanced and free from

commercial bias.
a. Strongly agree
b. Agree
c. Neutral What might be the barriers to change?
d. Disagree
e. Strongly disagree

7. The authors were knowledgeable and articulate in

presenting the material.
a. Strongly agree
b. Agree Do you use integrative approaches to treat your FM
c. Neutral patients? If so, what approaches do you use?
d. Disagree
e. Strongly disagree

8.The methods and format were appropriate and effective.

a. Strongly agree
b. Agree Are there any topics you would like to see addressed in
c. Neutral future educational activities?
d. Disagree
e. Strongly disagree

I claim (maximum 1.0) AMA PRA Category 1 Credit(s)TM Date of participation:

Name:

Degree and specialty:

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