Transcript Document

1
Update on Fibromyalgia
and Postherpetic Neuralgia
Steven Stanos, DO
1
Fibromyalgia
Pathophysiology
2
Mechanism
Description
Central sensitization
Amplification of pain in the spinal cord via spontaneous nerve
activity, expanded receptive fields, and augmented stimulus
responses
Abnormalities of
descending inhibitory
pain pathways
Dysfunction in brain centers (or the pathways from these centers)
that normally downregulate pain signaling in the spinal cord
Neurotransmitter
abnormalities
Decreased serotonin in the central nervous system may lead to
aberrant pain signaling, which may be due to serotonin transporter
polymorphism
Decreased dopamine transmission in the brain may lead to
chronic pain through unclear mechanisms
Neurohumoral
abnormalities
Dysfunction in the hypothalamic—pituitary—adrenal axis,
including blunted cortisol responses and lack of cortisol diurnal
variation, is associated with (but is not specific for) fibromyalgia
Psychiatric comorbid
conditions
Patients with fibromyalgia have increased rates of psychiatric
comorbid conditions, including depression, anxiety, posttraumatic
stress, and somatization; these may predispose to the
development of fibromyalgia
Abeles AM, et al. Ann Intern Med. 2007;146:726-734.
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Fibromyalgia
Possible Spinal and Supraspinal Effects
3
Descending Modulation
Facilitation
Substance P
Glutamate and
EAAs
NGF
Descending
modulatory
pathways
Inhibition
Descending
anti-nociceptive
pathways
Norepinephrine
and serotonin
(5HT1a,b)
Opioidsa
Ascending
pathways
Recent evidence suggests reduced µ-opioid receptor availability in patients with fibromyalgia; the arrows refer to the pathologic state.
Harris RE, et al. J Neurosci. 2007;27:10000-10006; Millan MJ, et al. Prog Neurobiol. 2002;66:355-474.
a
3
Fibromyalgia Pathophysiology
HPA Axis and Psychological Stress Connection
4
“TRIGGER EVENT”
Psychological
Distress
ALTERED HPA AXIS FUNCTION
Genetic
factors
Genetics
↓CRH
↓ACTH
↓Cortisol
Fibromyalgi
a
↓
Serotonin
↑
Substance P
McBeth J, et al. Arthritis Rheum. 2007;56:360-371.
Pain
4
Fibromyalgia
Overlap With Related Syndromes
5
Fibromyalgia
CFS
2%-4% of population;
defined by widespread
pain and tenderness
1% of population;
fatigue and 4 of 8
“minor criteria”
Pain and/or
sensory
amplification
Regional pain
syndromes
(eg, tension headache,
TMD, idiopathic LBP)
Psychiatric
disorders
MDD, OCD,
bipolar, PTSD,
GAD, panic attack
Somatoform
disorders
4% of population;
multiple unexplained
symptoms,
no “organic” findings
CFS, chronic fatigue syndrome; GAD, generalized anxiety disorder; LBP, low back pain; MDD, major depressive disorder;
OCD, obsessive-compulsive disorder; PTSD, post-traumatic stress disorder; TMD, temporomandibular disorders.
Clauw DJ, et al. Neuroimmunomodulation. 1997;4:134-153.
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Fibromyalgia
Shared Features With Depression
•
•
•
•
•
•
6
Strong genetic predisposition and similar comorbidity
Coaggregation in families
Cognitive disturbances
Dysfunction of the HPA axis
Chronic stress-induced cytokine expression in the brain
Central monoaminergic neurotransmission
http://www.medscape.com/viewprogram/17278_pnt. FPO
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Fibromyalgia
Recommended Diagnostic Work-up
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History of chronic,
widespread pain for ≥ 3 months
Rule out other conditions that may present with chronic
widespread pain (very much “operator dependent”)
General physical exam, neurologic exam, selected
laboratory testing (ESR, thyroid tests, avoid screening
serologic tests) Sleep and mood evaluation
Confirm presence of tender points
(Need 11of 18)
Confirm diagnosis of
fibromyalgia
ESR=erythrocyte sedimentation rate.
Adapted from: Burckhardt CS, et al. Guideline for the Management of Fibromyalgia Syndrome
Pain in Adults and Children; 2005
http://www.medscape.com/viewprogram/17278_pnt. FPO
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Fibromyalgia
Differential Diagnosis
8
• Rheumatic illness
– Systemic CTD (RA, myositis, SLE, PMR)
• False + ANA “pitfalls”
• Seronegative spondyloarthropathies
• Other chronic pain disorder (OA, spinal stenosis,
neuropathy)
• Infectious disease
– Lyme disease
– Viral (hepatitis C, HIV, “EBV”)
• Hypothyroidism
• Consider concurrent systemic illness and primary sleep
and mood disorders
CTD=connective tissue disease. RA=rheumatoid arthritis. SLE=systemic lupus erythematosus; PMR=polymyalgia rheumatica;
ANA=antinuclear antibodies; HIV=human immunodeficiency virus; EBV=Epstein-Barr virus.
http://www.medscape.com/viewprogram/17278_pnt. FPO
8
Fibromyalgia
Stepwise Treatment Algorithm
9
Step 1. Confirm diagnosis of fibromyalgia
a. Identify important symptom domains, their severity, and level of patient function
b. Evaluate for comorbid medical and psychiatric disorders
(eg, sleep apnea, OA, anxiety disorder)
c. Assess psychosocial stressors, level of fitness, and barriers to treatment
d. Provide education about fibromyalgia
e. Review treatment options
Step 2. Recommend treatment based on the individual evaluation
a. As a first-line approach for patient with moderate to severe pain, trail with evidence-based
medications, such as SSNRI (not for patients with bipolar disorder), α2δ ligand (especially
for patients with prominent sleep disturbance and anxiety),
or, if these do not work, SSRI or TCA
b. Evaluate for comorbid medical and psychiatric disorders
(eg, sleep apnea, OA, anxiety disorder)
Step 3. If not responding to medication alone, consider
CBT or group education
a. Encourage exercise according to fitness level (eg, goal of 30 to 60 minutes of low-moderate
intensity aerobic exercise [e.g., walking, pool exercises, stationary bike]
at least 2 to 3 times a week)
b. Encourage participation in supervised or group exercise
Arnold LM. Arthritis Res Ther. 2006;8:212.
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Fibromyalgia
Possible Two Types
10
Heterogeneity is largely due to differences in
depressive and anxiety symptoms
10
Visual Analog Scale
8
6
4
Fibromyalgia-Type I (n=27)
2
Fibromyalgia-Type I (n=34)
0
Pain
Fatigue
Stiffness
Morning
de Souza JB, et al. Rheumatol Int. 2008 Sep 27. [Epub ahead of print].
Tiredness
Anxiety Depression
10
Fibromyalgia
Genetic Influences
11
Serotonin-Related Genes
60
Healthy controls (n=110)
Gene Frequency, %
Patients with fibromyalgia (n=62)
50
40
a
30
20
10
0
Long/Long
Long/Short
Short/Short
Genotype at a SNP in the
regulatory promoter region of the
serotonin transporter gene (5-HTT)
• Short/Short subgroup showed
higher mean levels of depression
and psychological distress
• Polymorphism also associated
with anxiety-related personality
traits, diarrhea-predominant IBS,
and MDD
• Additional linkage between
fibromyalgia and a SNP in the
serotonin 2A receptor gene
(5-HT2A)
a
P=0.046.
SNP, single nucleotide polymorphism.
Bondy B, et al. Neurobiol Dis. 1999;6:433-439; Cohen H, et al. Arthritis Rheum. 2002;46:845-847;
Hoefgen B, et al. Biol Psychiatry. 2005;57:247-251; Offenbaecher M, et al. Arthritis Rheum. 1999;42:2482-2488;
Yeo A, et al. Gut. 2004;53:1452-1458.
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Fibromyalgia
Genetic Influences (cont’d)
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Dopamine- and Catecholamine-Related Genes
• Dopamine D4-receptor exon III repeat polymorphism
– Decreased frequency of 7-repeat allele in fibromyalgia
– Also associated with low novelty-seeking personality
• Altered dopamine D2-receptor function in fibromyalgia
• Catechol-O-methyltransferase (COMT)
– 1 of several enzymes that degrade catecholamines
• Dopamine, epinephrine, norepinephrine
– 1 variant associated with diminished µ-opioid system responses,
higher sensory and affective ratings of pain, and more negative
affective state
Buskila D, et al. Mol Psychiatry. 2004;9:730-731; Gürsoy S, et al. Rheumatol Int. 2003;23:104-107;
Malt EA, et al. J Affect Disord. 2003;75:77-82; Zubieta JK, et al. Science. 2003;299:1240-1243.
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Fibromyalgia
Family Study
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Relatives of
Fibromyalgia Probands, %
Relatives of
RA Probands, %
n=533
n=272
6.4
1.1
MDD
29.5
18.3
Bipolar I disorder
1.3
0.4
Bipolar II disorder
1.3
0.4
Disorder
Fibromyalgia
Major mood disorders
• OR of fibromyalgia in a relative of fibromyalgia proband vs
fibromyalgia in a relative of RA proband was 8.5a
– Primarily due to the effect of female relatives
• Relatives of fibromyalgia probands showed increased tender
point scores and decreased myalgic scores compared with
relatives of RA probandsb
a
95% confidence interval 2.8–26; P=0.0002.
P<0.0001 for both comparisons.
OR, odds ratio.
Arnold LM, et al. Arthritis Rheum. 2004;50:944-952.
b
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Fibromyalgia
Enhanced Pain Processing
NC-3sec
NC-5sec
FM-3sec
FM-5sec
• Lower mechanical
and thermal pain
thresholds (allodynia)
70
60
Pain Ratings, 0-100
14
• High pain ratings
for noxious stimuli
(hyperalgesia)
50
40
30
• Altered temporal
summation of painful
stimuli (wind-up)
20
10
0
T1
T5
T10
T15
3sec, interstimulus intervals of 3 sec; 5sec, interstimulus intervals of 5 sec; FM, fibromyalgia patient;
NC, normal control; T, tap stimulus.
Geisser ME, et al. Pain. 2003;102:247-254; Petzke F, et al. Pain. 2003;105:403-413;
Staud R. Arthritis Res Ther. 2006;8:208-214; Staud R, et al. Pain. 2001;91:165-175.
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Fibromyalgia
fMRI Findings
15
14
Pain Intensity
12
10
8
6
Fibromyalgia
4
Subjective pain control
2
Stimulus pressure control
0
1.5
2.5
3.5
4.5
Stimulus Intensity, kg/cm2
Similar pressure produced significantly greater activation at
13 regions in the patient group and 1 region in the control group
fMRI, functional magnetic resonance imaging.
N=16 patients with fibromyalgia and 16 matched controls.
Gracely RH, et al. Arthritis Rheum. 2002;46:1333-1343.
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Case Study
Introducing Katherine
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• 54-year-old financial consultant
• Presents to PCP for evaluation of pain that started 4
months ago in her shoulders and spread recently to
her hips, arms, and back
–Pain levels vary, 5-8/10
–She can’t work as efficiently as before
• History of symptoms consistent with IBS for the last 3
years, and recent depression, poor sleep and
chronic fatigue
• PCP suspects SLE, RA, or fibromyalgia
• What formal diagnostic, laboratory, and imaging tests may be helpful
when diagnosing Katherine?
– Does she have any fibromyalgia predisposing factors?
IBS, irritable bowel syndrome; PCP, primary care physician; RA rheumatoid arthritis; SLE, systemic lupus erythematosus.
16
Fibromyalgia
Comprehensive Assessment
Detailed history focusing on
illness that may mimic,
complicate, or occur
concurrently with fibromyalgia
Clinical diagnosis of
fibromyalgia based
on 1990 ACR criteria
Evaluate the severity of other
fibromyalgia symptoms:
fatigue, sleep disturbance,
mood/cognitive disturbance
Patient with
probable
fibromyalgia
Characterize pain type,
location, source, intensity,
duration, effects on QoL
17
Assess functional
status at initial and
subsequent visits
Analyze complete blood count,
ESR, muscle enzymes,
liver function, thyroid function
ACR, American College of Rheumatology; ESR, erythrocyte sedimentation rate; QoL, quality of life.
Burckhardt CS, et al. Guideline for the Management of Fibromyalgia Syndrome Pain in Adults and Children.
Glenville, Ill: American Pain Society; 2005.
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Fibromyalgia
ACR Diagnostic Criteria
18
• History (≥3 months) of
widespread pain
– Above and below the waist
– Bilateral
– In the axial skeleton
• Manual tender
point examination
– Pain in ≥11 of 18 specific
fibromyalgia tender points on
digital palpation
– ~ palpation force: 4 kg/1.4 cm2
Okifuji A, et al. J Rheumatol. 1997;24:377-383.
Wolfe F, et al. Arthritis Rheum. 1990;33:160-172.
http://www.fibromyalgia-symptoms.org/fibromyalgia_diagnosis.html. Accessed August 1, 2008.
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Key Fibromyalgia Domains
Patient Perspectives
19
• Physical
– Pain
– Fatigue
– Disturbed sleep
• Emotional/cognitive
– Depression, anxiety
– Cognitive impairment (decreased concentration, disorganization
– Memory problems
• Social
– Disrupted family relationships
– Social isolation
– Disrupted relationships with friends
• Work/activity
– Reduced activities of daily living
– Reduced leisure activities/avoidance of physical activity
– Loss of career/inability to advance in career or education
Arnold LM, et al. Patient Educ Couns. 2008;73:114-120.
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Katherine
Diagnosis
20
• Based on normal laboratory results and
comprehensive examination, PCP rules out RA,
PMR, and SLE
• Digital palpation reveals pain at 14 of the
18 tender points
• She reports having trouble concentrating
• PCP diagnoses fibromyalgia, recommends a support
group, and provides educational material to help
Katherine understand the disease
Would your treatment plan differ if Katherine reported 9 of 18 tender points?
Are cognitive deficits common in patients with fibromyalgia?
PMR, polymyalgia rheumatica.
20
Fibromyalgia
30
10
10
40
20
Verbal Fluency
Age-matched controls
Correct Answers
Number of
Words Produced
1
80
b
2
Free Recall
80
a
3
20
Working Memory
Capacity
60
4
d’
20
21
a
60
a
40
20
Verbal Knowledge
Older subjects
Recognition Memory
Summed Score
From Speed Tasks
30
a
Recalled Words
Correct Responses
Cognitive Dysfunction
160
120
80
40
Information-Processing
Speed
Fibromyalgia patients
a
P<0.05 compared with age-matched controls; b P=0.055 compared with age-matched controls.
d’, a measure of how effectively a subject can discriminate an item as new or previously studied.
N=23 fibromyalgia patients, 23 age-matched controls, and 22 education-matched controls who were 20 years older.
Park DC, et al. Arthritis Rheum. 2001;44:2125-2133.
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Fibromyalgia
Dually Focused Treatment
Symptoms of pain, fatigue, etc
• Nociceptive processes
• Neuroendocrine and sleep dysfunction
22
Pharmacologic
therapies to
improve symptoms
• Disordered sensory processing
Functional consequences of symptoms
• Increased distress
• Decreased activity
• Isolation
• Poor sleep
Nonpharmacologic
therapies to
address dysfunction
• Maladaptive illness behaviors
Clauw DJ, et al. Best Pract Res Clin Rheumatol. 2003;17:685-701(B).
22
Fibromyalgia
Interventions
23
Patient Education
Explain what the condition is
and what it is not
CAM
Cognitivebehavioral,
alternative therapies
Physical Therapy
Exercise programs
Multimodal Therapeutic
Strategies for Fibromyalgia
Psychological
Support
Psychotherapy,
support groups
Pharmacotherapy
Address Comorbidities
SNRIs, TCAs,
anticonvulsants, tramadol
Sleep dysfunction,
depression, anxiety
CAM, complementary and alternative medicine; SNRI, serotonin–norepinephrine reuptake inhibitor;
TCA, tricyclic antidepressant.
Burckhardt CS, et al. Guideline for the Management of Fibromyalgia Syndrome Pain in Adults and Children.
Glenville, Ill: American Pain Society; 2005.
23
Fibromyalgia
Nonpharmacologic Therapies
• Strong evidence
– Education
– Aerobic exercise
– Cognitive-behavioral
therapy
• Modest evidence
– Strength training
– Hypnotherapy,
biofeedback,
balneotherapy
24
• Weak evidence
– Acupuncture
– Chiropractic, manual,
and massage therapy
– Electrotherapy
– Ultrasound
• No evidence
– Tender point injections
– Flexibility exercise
Burckhardt CS, et al. Guideline for the Management of Fibromyalgia Syndrome Pain in Adults and Children.
Glenville, Ill: American Pain Society; 2005; Goldenberg DL, et al. JAMA. 2004;292:2388-2395.
24
Fibromyalgia
Aerobic Exercise
Exercise
25
Control
– Nearly universally beneficial
a
30
• Tolerance, compliance,
and adherence are
biggest hurdles
• Programs should be
individualized
Mean Change
in Parameter, %
25
20
a
15
10
– Begin several months after
pharmacologic therapy
– Begin with low-impact
exercises
5
0
-5
-10
• Benefits first reported 30
years ago
Aerobic
Performance
Mean Tender
Point Pain
Threshold
Pain Intensity
a
P<0.001; meta-analysis of 4 independent studies.
Busch AJ, et al. Cochrane Database Syst Rev. 2002, Issue 2. Art. No. CD003786. doi:10.1002/14651858.CD003786.
McCain GA, et al. Arthritis Rheum. 1988;31:1135-1141.
25
Fibromyalgia
Cognitive-Behavioral Therapy
• Longitudinal trials show
reduced pain severity and
improved function
Thoughts
Physical
Response
26
Feelings
• Systematic reviews
demonstrate reduced pain
and fatigue, improved mood
and function
• Improvements also seen
with meditation, relaxation,
stress management
Behavior
Goldenberg DL, et al. JAMA. 2004;292:2388-2395.
Hadhazy V, et al. J Rheumatol. 2000;27:2911-2918.
Williams DA. Best Pract Res Clin Rheumatol. 2003;17:649-665.
• Effects depend heavily
on therapist and program
26
Fibromyalgia
CBT vs Routine Care
27
% of Patient Responses
30
CBT (n=62)
Routine (n=60)
25
20
15
10
5
0
Physical
Functioning or
2.9, p<0.05
*Statistically significant.
OR=odds ratio.
Williams DA, et al J Rheumatol. 2002; 29(6):1280-1286.
http://www.medscape.com/viewprogram/17278_pnt. FPO
Sensory Pain
Affective Pain
27
Fibromyalgia
Pharmacologic Therapies
• Strong evidence
– Dual-reuptake inhibitors
• Tricyclic compounds
• SNRIs
– Anticonvulsants
• Modest evidence
–
–
–
–
Dopamine agonists
Gamma hydroxybutyrate
Tramadol
SSRIs
28
• Weak evidence
–
–
–
–
Growth hormone
5-hydroxytryptamine
Tropisetron
SAMe
• No evidence
–
–
–
–
Opioids
Corticosteroids
NSAIDs
Benzodiazepine and
nonbenzodiazepine
hypnotics
NSAID, nonsteroidal anti-inflammatory drug; SAMe, S-adenosyl-L-methionine; SSRI, selective serotonin reuptake inhibitor.
Modified from: Burckhardt CS, et al. Guideline for the Management of Fibromyalgia Syndrome Pain in Adults and Children.
Glenville, Ill: American Pain Society; 2005; Goldenberg DL, et al. JAMA. 2004;292:2388-2395.
28
Fibromyalgia
Dual-Uptake Inhibitors: TCAs
Outcome Measure
1.0
0.5
Stiffness
Tenderness
Sleep
Fatigue
Pain
-0.5
M.D. Global
Assessment
0.0
Patient Global
Assessment
Effect Size, Standard Deviation
1.5
29
• TCAs associated with
effect sizes substantially
larger than 0 for all
measurements
• Largest improvements
in sleep quality
• Most modest
improvements in
stiffness, tenderness
• Common AEs include
sedation, anticholinergic
side effects, weight gain
AE, adverse event.
Box plot of effect size in 9 controlled studies of TCA treatment of fibromyalgia.
Observations lying beyond the 5th and 95th percentiles.
Arnold LM, et al. Psychosomatics. 2000;41:104-113.
29
Fibromyalgia
Dual-Uptake Inhibitors: Cyclobenzaprine
Favors Placebo
Favors Treatment
Bennett (1988)
• Often classified as
muscle relaxant, but
actually structurally a
tricyclic compound
• Moderate improvements
noted for sleep after
4, 8, and 12 weeks of
treatment
Carette (1994)
Quimby (1989)
Overall (95% Cl)
0
30
3.0 (95% CI: 1.6-5.7)
1
25
Effect Size on Dichotomous Outcomes of Improvement
CI, confidence interval.
Tofferi JK, et al. Arthritis Rheum. 2004;51:9-13.
– Modest improvement
in pain levels observed
only at 4 weeks
• Common AEs include
sedation, anticholinergic
side effects, and
weight gain
30
Fibromyalgia
Dual-Uptake Inhibitors: SNRIs
31
• Do not interact with adrenergic,
cholinergic, or histaminergic receptors, or
sodium channels
– Duloxetine
• FDA approved for fibromyalgia, GAD,
MDD, and pain associated with DPN
Duloxetine
– Venlafaxine
• FDA approved for GAD, social anxiety disorder,
MDD, and panic disorder
• Ineffective in an RCT for fibromyalgia
– Milnaciprana
Venlafaxine
Milnacipran
a
New Drug Application submitted to the FDA for fibromyalgia.
Burckhardt CS, et al. Guideline for the Management of Fibromyalgia Syndrome Pain in Adults and Children.
Glenville, Ill: American Pain Society; 2005.
31
Fibromyalgia
SNRIs: Proposed MOA
Perception
32
Inhibition
• Augmented descending inhibition
via amplification of norepinephrine
and serotonin signaling
Modulation
Ascending
pathways
Descending
modulatory
pathways
Transduction
Transmission
MOA, mechanism of action.
32
Fibromyalgia
Duloxetine in Randomized Trials
Mean Difference
IV, Fixed, 95% CI
33
Mean Difference
IV, Fixed, 95% CI
Arnold (2005)
Russell (2008)
Overall (95% Cl)
-2
-1
Favours placebo
1.07 (0.66, 1.47)
0.89 (0.49, 1.30)
0
1
2
Favors duloxetine 60 mg
Sultan A. BMC Neurology. 2008;8:29.
-2
-1
Favours placebo
0
1
2
Favors duloxetine 120 mg
33
Fibromyalgia
Anticonvulsants: 2 Ligands
• Drugs that diminish neuronal
excitability
α2
N
34
• Bind to 2 subunit of voltage-gated
calcium channels
γ
δ
– Reduce calcium influx, thereby
inhibiting neurotransmitter release
α1
• FDA indications
N
c
c
c
– Fibromyalgia (pregabalin)
– Neuropathic pain associated with
DPN (pregabalin)
– PHN (gabapentin, pregabalin)
– Adjunctive therapy for partial-onset
seizures in adults (pregabalin) or
adults and children (gabapentin)
Arnold LM, et al. Arthritis Rheum. 2007;56:1336-1344; Crofford LJ, et al. Arthritis Rheum. 2005;52:1264-1273;
Van Petegem F, Minor DL. Biochem Soc Trans. 2006;34:887-893.
34
Fibromyalgia
Anticonvulsants: Pregabalin
>30% responders, %
60
a
48.4
50
37.9
40
30
35
27.1
31.3
• Common AEs (>10%) in
the 450 mg-per-day
group: dizziness,
somnolence, headache,
dry mouth, and
peripheral edema
20
10
0
Placebo
• Significant improvements
seen in MOS-sleep
problem index, total
SF-MPQ score, MAF
global fatigue index,
4 SF-36 domains
150
300
450
Pregabalin Dose, mg/d
a
P=0.003 compared with placebo after 8 weeks of treatment using 0-10 pain scores (N=529).
MAF, multidimensional assessment of fatigue; MOS, medical outcomes study;
SF-MPQ, McGill Pain Questionnaire-Short Form.
Crofford LJ, et al. Arthritis Rheum. 2005;52:1264-1273.
35
Fibromyalgia
Pregabalin/Gabapentin: Proposed MOA
Perception
36
Facilitation
• Decrease substance P release
in inflammatory states
• Inhibit substance P–induced
glutamate release
Modulation
Ascending
pathways
Descending
modulatory
pathways
Transduction
Transmission
Fehrenbacher JC, et al. Pain. 2003;105:133-141; Maneuf YP, et al. Pain. 2001;93:191-196.
36
Katherine
Follow-Up
37
• Pain has increased in the 2 weeks since last
visit to PCP
• Stopped working
• Rarely leaves the house because of depression
• Despite spending much of the day in bed,
Katherine reports feeling tired and run-down
• Based on Katherine’s presentation, how would you proceed with her treatment?
• In addition to treatment of pain, should Katherine be prescribed medication for
any other condition?
• What would constitute “successful” treatment?
37
Fibromyalgia
Interdisciplinary Pain Management
38
Integrated and Coordinated
Pain Specialist
Nurses
Psychiatrist
Spine Surgeon
Primary
Clinician
Neurologist
Pharmacist
Physiatrist
Social Worker
Psychologist
Anesthesiologist
Occupational Therapist
Physician Assistant
Physical Therapist
38
Fibromyalgia
Conclusions
39
• Wide range of data support the notion that fibromyalgia
is a chronic pain disorder characterized by augmented
central pain processing
• Diagnosis should be based on ACR criteria,
comprehensive assessment, exclusion of other potential
disorders associated with widespread pain, and
evaluation of the range of symptomology
• Due to its complexity, it is best understood from a
multidisciplinary perspective
– To address pain and relevant comorbidities, treatment should
include both pharmacologic and nonpharmacologic modalities
39
Case: Ms. Karibean
40
• 82 year old female. Chronic left
abdominal pain. Rash from “insect bite”
she suffered while on a cruise healed 4
months ago. Increase pain and sensitivity
to light touch from clothing in same area.
Pain worse at night, difficulty falling
asleep and frequent awakenings due to
pain.
• Ibuprofen, Tylenol #3 not working.
40
Primary Infection, Latency, and
Recurrence of Varicella Zoster Virus 41
1. Entry
4. Latency
(sensory ganglion)
5. Herpes
zoster
(shingles)
2. Spread
3. Varicella
infection
(chickenpox)
Straus SE, et al. In: Fitzpatrick's Dermatology in General Medicine. 6th ed. New York, NY: McGraw-Hill Professional; 2003:20702080.
41
42
42
The Spectrum of Pain in Herpes
Zoster
43
Rash Onset
Prodrome
Onset
Typically
≤1 wk
Pain
Cessation
Rash
Healed
2-4 wk
Acute pain
Can Be Years
Postherpetic neuralgia (PHN)
1 mo
3 mo
6 mo
Irving GA, Wallace MS. In: Pain Management for the Practicing Physician. New York, NY: Churchill Livingstone; 1997:141-147.
Bowsher D. J Pain Symptom Manage.1996;12:290-299.
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Pain Distribution in PHN
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• Thoracic dermatomes are affected in the
majority of patients (>50%)
• Other dermatomes are affected less often
– Trigeminal dermatome
– Lumbar dermatome
– Cervical dermatome
Straus SE, et al Fitzpatrick's Dermatology in General Medicine. 6th ed. New York, NY: McGraw-Hill Professional; 2003.
44
45
45
Considerations for Comprehensive
Management
• Biologic intervention
– Pharmacologic and/or
nonpharmacologic
approaches
• Psychological
intervention
– Address mood and
sleep disturbances
– Enhance coping skills
• Social/rehabilitative
intervention
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– Family/social support
– Address work issues
– Physical rehabilitation
• Physical/occupational
therapy
• Home exercise
program
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Some Treatment Considerations in
Neuropathic Pain of PHN
Drug Factors1,2
Patient Factors1,2
• Efficacy
• Safety
• Potential for AEs
• Tolerability
• Drug interactions
• Monotherapy vs.
combination therapy
• Treatment costs
• Comorbidities
• Mental status
• Risks of drug misuse/
abuse
• Risks of unintentional
overdose
• Adherence
• Prior therapies
edication costs
AEs=adverse events.
1. Dworkin RH, et al. Pain. 2007;132:237-251.
2. Gilron I, et al. CMAJ. 2006;175:265-275.
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Evidence-Based Medications for
Neuropathic Pain of PHN
Medication
Beginning Dose
Titration
Maximum Dose
TCAs
25 mg QHS
Increase by 25 mg every 3–7
days
150 mg/d, keep
<100 ng/mL
Duloxetine
30 mg QD
Increase to 60 mg QD after
1 week
60 mg BID
Venlafaxine
37.5 mg QD or BID
Increase by 75 mg each week
225 mg daily
Gabapentin*
100–300 mg QHS or
TID
Increase by 100–300 mg TID
every 1–7 days
3600 mg/d
Pregabalin*
50 mg TID or 75 mg
BID
Increase to 300 mg daily after
3–7 days, then by 150 mg/d
every 3–7 days
600 mg/d
Lidocaine patch 5%*
Max. 3 patches daily
for max. 12 hours
None needed
Max. 3 patches,
12 hours
Opioids
10–15 mg morphine
equivalents q4h or prn
After 1–2 weeks, convert total
None
daily dose to long acting
Tramadol HCl
50 mg QD or BID
Increase by 50–100 mg/d in
divided doses every 3–7days
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300–400 mg/d
*Only lidocaine patch 5%, gabapentin, and pregabalin have indications specific for the treatment of PHN pain.
Dworkin RH, et al. Pain. 2007;132:237-251.
48
Lidocaine Patch 5%: Blood Levels
Various Applications
49
5
µg/mL
4
3
2
1
0
Lidocaine*
patch 5%
2 mg/min
Infusion
Arthroscopic
Knee Surgery
2 g of 5%
Cream to Burns
Antiarrhythmic
Level
Toxic Level
*In normal, healthy volunteers
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