Fibromyalgia & Myofascial Pain A Case for Central ... Audette.pdf · Pathology is Neuromuscular...
Transcript of Fibromyalgia & Myofascial Pain A Case for Central ... Audette.pdf · Pathology is Neuromuscular...
Fibromyalgia & Myofascial PainA Case for Central Sensitization
Joseph F. Audette MA, MDChief, Department of Pain Medicine
Harvard Vanguard Medical Associates
What is Fibromyalgia (FMS) ?Also called fibrositis ( 1900-1989 )Fibromyalgia (1990-)Common, affecting 2% of the US
populationWomen: 3.4% Men: 0.5% (Wolfe, 1995)
Children: 1.2% (Clark, 1998)
2nd most common musculoskeletal disorder seen by rheumatologists
1990 American College of Rheumatology Criteria
History of widespread pain: left, right, above and below the waist, axial painPresent for at least three monthsPain in 11 out of 18 anatomically
defined tender points when palpated with 4 kg/cm2 of force
Diagnosis of Inclusion
1990 Müller & Lautenschlager Criteria
Spontaneous pain in the musculature, in the course of tendons and insertions with typical locations near the spine and/or in the extremities, including the jaw region Longer than 3 months durationIn at least three different body regions
1990 Müller & Lautenschlager Criteria
Increased pressure sensitivity at 12 / 24 tender points with 2 kg/cm2 of forceAssociated autonomic and functional
symptoms (i.e.,sleep disturbances)Psychopathological findings including
neurosis, depression and anxietyNormal laboratory tests
Fibromyalgia and Costs to Society
In the States: 30% shorter work hours or less demanding work15% get some form of disability
paymentThe direct cost of FMS is in excess
of $16 billion annuallyWolfe F et al: Arthritis Rheum
1997;40:1560-1570
Causes of Widespread PainWhiplashMyofascial Pain SyndromeStatin drugsOpioid Induced HyperalgesiaHypothyroidismParasitic infectionsHepatitisOther rheumatic diseases
FibromyalgiaA fancy name for “chronic
widespread pain”
Patient with pain
Doctor, why do I have pain?
Pain is confirmed by tender points Dx: fibromyalgia
Because you have fibromyalgia
You have pain, because you have pain
Dommerholt J. J Musculoskeletal Pain 2000;8(4):41-47
Heim C, et al. Psychoneuroendocrinology. 2000;25:1-35.
Fibromyalgia & Stress Related Disorders
Hypocortisolism common to allDepressionPTSDPersian gulf syndromeInsomniaChronic fatigueChronic pelvic pain
MMPI and Somatoform Disorder
Copenhagen Declaration, 1993Patients with FMS should not be
treated as hypochondriacsPsychological distress is not a cause
for muscular pain and tendernessChronic Pain and tenderness is a cause
of psychological distress
Psychiatric Co-morbidityControlled studies using standard
psychologic instruments have concluded:No greater psychologic symptoms in
FMS patients than controlMajority of FMS patients do not have
an active psychiatric illnessNo evidence for a specific personality
type for FMS patientsHudson, Bailliere Clin Rheumatol, 1994
McBeth et al., Curr Rheumatol Rep, 2001
Kersh BC, Bradley LA, et al. Arthritis Rheum. 2001 Aug;45(4):362-71.
FMS Patient
Those FMS patients that visit a Rheumatology office did have a significantly higher psychiatric co-morbidity than did community FMS individuals.
Clauw DJ. J Musculoskel Med. 1999;Supplement:S7.
Tender PointsHigh tender point count may indicate:
More somatic symptoms
More severe fatigue
Low levels of self-care
Increased medical care usage
Higher level of distress
DEGREE OF FIBROMYALGIANESSWolf F. Ann Rheum Dis. 1997;56(4):268–71.
Who Gets Fibromyalgia?
Mostly women (9:1)20 to 60 years oldTypically has symptoms for 5 years
before diagnosisRheumatoid arthritis/lupusNo unique physical characteristicsAdolescents
Gender differences and painFemales more sensitive than males in all
sensory systems (Riley et al. Pain 1998; 74: 181-187.)
Most dramatic when tested with pressure pain threshold
Possible influence of sex hormones
Socio-cultural factors, including patient-doctor relationships
Psychophysical issues
Gender Differences and Chronic Pain
Serotonin synthesis fast7-fold drop in
serotonin synthesis after removal of tryptophanLow pain sensitivity
Serotonin synthesis slow42-fold drop in
serotonin synthesis after removal of tryptophanHigh pain sensitivity
Nishizawa S, Benkelfat C, Young SN et al: Differences between males and females in rates of serotonin synthesis in human brain. Proc Natl Acad Sci USA,
1997;97:5308-5313
Males Females
Fibromyalgia
HeadachesDysmenorrhea
ChronicFatigue
Syndrome
Psychological Problems
Depression
Dyspareunia SinusitisPanic Disorder
RestlessLeg
Syndrome
InterstitialCystitis
IrritableBowel
Syndrome
Diagnosis of ExclusionRule out inflammatory arthritisDifferential diagnosis includes: myofascial
pain, hypothyroidism, hepatitis, nutritional disorders, somatoform disorder, depression, otherLaboratory tests are performed to exclude
mimics of FMS: CBC & LFTsESR to rule out an inflammatory disorder TSH, Vit D, B12, Fe levels
Lyme Disease
Differential Diagnosis
HypermobilitySyndrome
MetabolicDeficiencies
Geel SE. Seminars Arth Rheum. 1994;23(5):347.
The Evidence: Muscle Dysfunction in Fibromyalgia
Biopsy results (Bengtsson Arthritis Rheum. 1986;29:817.)Decrease in high energy phosphates
31P NMR spectroscopy of muscle (Jacobsen S, et al. J Rheumatol. 1992;19(10):1600-3)
No difference in phosphate energy stores compared to sedentary controls
Lack clear evidence to conclude there is a muscle abnormality
The Evidence: CNS Dysfunction in Fibromyalgia
Hyperalgesia & central sensitizationSerotonin deficiencyCSF elevation SP, NGFMuscle Biopsy shows elevated SP
(De Stefano J Rheumatol. 2000)
Russell IJ. J Musculoskel Med. 1999;Supplement:S13.
A Central Processing Problem?Comparison of nail bed pressure in
normals vs fibromyalgia patientsSame Stimulus in both groups caused
markedly different brain activation patternHigher Stimulus in normals to cause same
subjective pain levels as found with lower stimulus in fibro patients caused similar activation patterns in both groups
Supports the hypothesis that FM is characterized by cortical or subcortical augmentation of pain processing
Gracely, Arth Rheum, 2002
Evidence for Central Sensitization
Enhanced Temporal Summation with cutaneous thermal stimuli (Staud R, et al. Pain 2001;91:165.)
Heat probe at 51.5°C, 2 and 5s intervalsMechanical Allodynia found to
pressure < 4kg/cm2
IV Ketamine reverses Hyperalgesia and Lowers Pain Threshold over TP (Graven-Nielsen T, et. al. Pain 2000;85:483.)
NMDA Receptor and FMS
Abnormal CSF levels of SP, NGF, and 5HT suggest loss of descending inhibition on DH neurons Windup seen with temporal
summation dependent on NMDA activationResponse to Ketamine suggests
antagonism of NMDA receptor important to diminish pain associated with FMS
Opioid Hyperalgesia:NMDA Receptor Activation via PKCAntagonized by KetamineEvidence suggests PKC induction even
by brief intra-op exposureMay explain failure of preemptive
analgesia Opioid Hyperalgesia Found in methadone maintenance
patients (Doverty M, et al. Pain 2001;90(1-2):91.)
Believed to be linked to NMDA receptor activation
Opioids vs. KetamineNo RCT assessing oral opioids in
FMSDouble blind comparison of IV
Morphine (0.3mg/kg) Ketamine (0.3mg/kg) Lidocaine (5mg/kg) (Bengtsson SJ, et al. Scand J Rheum. 1995;24(6):360.)
Results
Morphine: no effect on pain intensity, pressure pain or exercise enduranceLidocaine: affected pain intensity
during and briefly after infusionKetamine: significantly improved all
three outcome measures
Medications for Fibromyalgia Syndrome
Tricyclic AntidepressantsAmitriptyline^^
Nortriptyline^^
Cyclobenzaprine ^
SSRIsFluoxetine 20-80 mg with orwithout tricyclic at bedtime ^
Sertraline 50 mg ^
SNRIsVenlafaxine 75 -225 mg/day^
Duloxetine 60 mg ^^*Milnacipran 50-100 mg BID^^*
Anti-convulsantsPregabalin 450 mg/d^^*Gabapentin 1200-2400 mg/d^
AnalgesicsTramadol 200-300 mg/d^^
^ Modest Evidence for Efficacy^^Strong Evidence for Efficacy
*FDA approved
Arnold LM, et al. J Pain. 2008 Jun 2.
Pregabalin and FibromyalgiaRCT of pregabalin 750 FMS patients assigned to
pregabalin (300 mg/d, 450 mg/d, 600 mg/d) or placebo, administered twice daily for 14 weeks.ResultsSignificant improvement in pain scores (P < .001: 300 mg/d, -0.71; 450 mg/d, -0.98; 600 mg/d, -1.00). Significant improvements in FIQ score: 450
mg/d (P = .004) and 600 mg/d (P = .003) All 3 doses of pregabalin were associated with
significant improvement in sleep
Arnold LM, et al. 1: Arthritis Rheum. 2007 56(4):1336-44.
Gabapentin and FibromyalgiaRCT compare gabapentin (1,200-2,400 mg/day)
(n=75 patients) with placebo (n=75 patients) for 12-week
Significant improvement in the BPI average pain severity score (P=0.015; estimated difference between groups at week 12=-0.92 [95% confidence interval -1.75, -0.71]).
Gabapentin compared with placebo also significantly improved the BPI average pain interference score, the Fibromyalgia Impact Questionnaire total score but not the mean tender point pain threshold or the Montgomery Asberg Depression Rating Scale.
Low Dose Naltrexone31 woman with fibromyalgia in
RCT crossover study 2 week observation followed by
either placebo or 4.5 naltrexoneNaltrexone group had a more
significant reduction in pain (28% vs. 18%, P=0.016)Significant improvement in mood and satisfaction
with life (p<0.05)Younger J, et al. Arthritis & Rheum 2013;65(2):529–538
Myofascial Pain vs. Fibromyalgia
Is Fibromyalgia on one extreme of a continuum of central nervous system and muscle dysfunction that begins with more localized myofascial pain and can end with widespread pain if not appropriately diagnosed and treated?
Distribution of active trigger zones (n=100)
Regional 1-2 quadrants
55%
Widespread 3-4 quadrants
45%
Gerwin, R.. A study of 96 subjects examined both for fibromyalgia and myofascial pain (abstract). J Musculoskeletal Pain 1995 3: 121.
Myofascial vs. Fibromyalgia
Symptoms Fibromyalgia Myofascial Pain Pain Bilateral More Common Less Common Sleep Disturbance More Common Less Common Daytime Fatigue More Common Less Common Depression More Common Less Common Irritable Bowels More Common Less Common Urinary Frequency More Common Less Common Dysmenorrhea More Common Less Common Exercise Intolerance More Common Less Common Chronic Sinusitis More Common Less Common
Unique Characteristics of Muscle pain Aching, cramping pain, difficult to
localize and referred to deep somatic tissuesActivates unique cortical structures Inhibited more strongly by descending
pain-modulating pathwaysActivation of muscle nociceptors is
much more effective at inducing neuroplastic changes in dorsal horn neurons
Historical Considerations Samuel Solly, Esq., F.R.S. (1863) description
of Scriveners’ PalsyThe pain was a burning, uncomfortable feeling
between the knuckles... extending occasionally to the shoulder after writing about an hour...At times, the symptoms were very much more violent, and I frequently...had to put down my pen, feeling it quite impossible to continue work in that state....[Even after an extended rest] ...the burning sensation returned with great force, and extended all over the back part of my shoulder, and when I wrote I could feel it creeping down my side and under my shoulder-bone....accompanied by the old symptoms of burning and bursting..... it troubled me in the night, frequently keeping me awake for hours....
Cause of Underlying Pathology
Irritable Endplate TheoryPrimary Pathology in Muscle
Muscle Spindle DysfunctionPathology is Neuromuscular
Neuropathic TheoryPrimary pathology in CNS
Integrated Neuromuscular Theory
Travell, J.G., Simons, D.G., & Simons, L.S. (1999)Myofascial pain and dysfunction: The trigger point manual: Volume one, Upper half of body (2nd ed.)Baltimore, MD: Williams & Wilkins
Problems with Classic Irritable Endplate Theory
Latent Trigger Points: The Human ConditionWhat is different about a taut band in
someone with active pain at rest versus the majority of the adult population who has pain only on deep palpation
The Local Twitch Response
Audette JF, Wang F, et al. Am J Phys Med Rehabil. 2004 83(5):368-74.
Effect of Unilateral Dry Needling on an Active Trigger Point
Bilateral Twitch Response
Audette JF, et al. Am J Phys Med Rehabil. 2004 May;83(5):368-74.
Peripheral MechanismsMuscle nociceptors possess a
multitude of receptors for endogenous pain-producing and sensitizing agentsMuscle tenderness is mainly due to the
sensitization of muscle nociceptors by H+, PG’s, bradykinin and serotonin
Neurosecretory Properties of Unmyelinated Sensory Afferents
Convergence of Input to WDR Neuron
Dorsal Root Reflexes
Outflow on dorsal rootsInitial C-fiber
activityTissue-level peptide
releasePeng YB J Neurophysiol 2001
Dorsal Root Reflexes
Outflow on dorsal rootsInitial C-fiber
activityTissue-level peptide
releasePeng YB, J Neurophysiol 2001;86: 49-58.
Results of Joint Irritation on Muscle
Lowering of activation thresholds for muscle nociceptors with joint inflammationDevelopment of hyperalgesia &
Peripheral sensitizationGrigg P, Schaible,H, Schmidt R. Mechanical sensitivity of group III and IV afferents from posterior articular nerve in normal and inflamed cat knee. J Neurophysiology 55:635-643, 1986
Shah JP et al. J Appl Physiol. 2005 Nov;99(5):1977-84.
Microdialysis/Acupuncture Needle
Fluid in
Fluid outSolute exchange
surface – dialyzer membrane set 0.2 mm from the needle tip
Delivery tubes
Microdialysis/Acupuncture Needle
Chief Variables
Pain pressure threshold (PPT) -Fischer algometerlevels of pH, substance P,
calcitonin gene-related peptide (CGRP), bradykinin, norepinephrine, tumor necrosis factor α (TNF-α), and Interleukin -1 beta (IL-1β)
Measurement Active MTrPs compared to Latent MTrPs and toNormal Muscles
Pressure Pain Threshold (PPT)
P < 0.03
P < 0.08
pH
Substance P, CGRP
P < 0.01
Results
Bradykinin
Serotonin
Norepinephrine
Tumor Necrosis Factor (TNF-)
Interleukin (IL-1)
P < 0.01
P < 0.01
P < 0.01
P < 0.001
P < 0.001
Results
Substance P
0
50
100
150
200
250
300
350
400
0:00 2:24 4:48 7:12 9:36 12:00 14:24 16:48
Time
pg/m
l Gr.1Gr.2Gr.3
Substance P
CGRP
0
50
100
150
200
250
300
350
400
0:00 2:24 4:48 7:12 9:36 12:00 14:24 16:48
Time
pg/m
l Gr.1Gr.2Gr.3
CGRP
Goal of ExaminationFind the Cause of the Sensitized
SegmentJoint
Facet or SI jointShoulder or HipJaw
MuscleTraumaRepetitive StrainEmotional Holding Patterns
VisceraUterus, OvariesGallbladder
Myofascial Exam:Palpation, Palpation, Palpation!
Taut Band with Twitch response causing reproducible referral patternLoss of Range of MotionThermal PropertiesDermatographiaNon-Dermatomal Sensory LossWeakness without Neurologic
Findings Recognized Pain
Structural Assessment
Treatment: Trigger Point InjectionsNo high-quality, controlled trials
(Hong et al., Arch Phys Med Rehab 1996; Figuerola ML, et al. Funct Neurol 1998)Highly variable use by physiciansHighly variable response by patientsLidocaine, corticosteroid, botulinum,
“dry needling”Acupuncture & Fibro (Martin DP Mayo Clin Proc
2006;81:749-57)
Recent RCT supports use to reduce pain, anxiety, and fatigue
Treatment: Exercise
Exercise is routinely recommended – truly conventional
Conventional teaching – aerobic exercise at least 3 times a week
Referral to physical therapy common
Treatment: Exercise• Richards, 2002 – n=132; 35% vs. 18%
(aerobics. vs. relaxation); Improved on self assessment
• Jones, 2002 – n=62; strengthening vs. stretching 2x better in former
• Rooks, 2002 – n=15; CV & strengthening program well tolerated, compliance was 80%, improved from baseline
Rehab Options with Potentially More Lasting BenefitSelf Management TechniquesStretching and Strengthening with
relaxation/breathing methodsMeditationPostural Realignment/ PNF TechniquesPacingAerobic Conditioning
Joint Mobilization followed by above self management methods
Pharmacological InterventionsAcute PhaseHigh Dose NSAID’sOpioids? Steroids?Muscle Relaxant QHSCyclobenzaprine (Flexeril)Tizanidine (Zanaflex)
Pharmacological Interventions II
Acute Phase to Sub-Acute PhaseTCA in evening titrate to restorative
sleepReduce Central Facilitation
Consider Daytime Muscle Relaxant Tizanidine BaclofenClonazepam
Plus Minus NSAID’s
Combine with Manual Therapies
Goal to Diminish Afferent Drive and Facilitate Rehabilitation Process
Trigger Point InjectionsAcupunctureMassage TechniquesManipulative TherapiesJoint Injections
Pharmacological Interventions IIISub-Acute to ChronicAdd anticonvulsant -central facilitation
Gabapentin* (Neurontin 1800-4000 mg/day)Topiramate* (Topamax 100-600 mg/day)Levetiracetam* : (Keppra 500-3000, BID)Tiagabine* (Gabitril 2-24 mg/day)Zonisamide* (Zonegran 100-400 mg/day)Pregabalin* : (Lyrica 75 –600, TID)
If Depressed/Anxious Mood PredominantCalm Descending Drive from higher
CentersSSRI, SSNRI, Wellbutrin, AnxiolyticsBehavioral Psychology *Not approved by FDA for this use.
Multi-faceted Approach for Chronic Soft Tissue Pain
Spray/StretchStrain/counterstrainMuscle energyJoint Mobilization“Dry needling” - trigger
point acupunctureTrigger point injectionsMedicationsBotox injections
Orthotics, shoe modificationCounselingBehavioral
managementRelaxationImageryHypnosisCoping skillsAcupressure
Failure of Standard Treatment for Soft Tissue Pain
Failure to identify and eliminate underlying causeStructural UnderpinningsSystemic IllnessCause of Sensitized Segment
Psychological FactorsGenetic Predisposition
SummaryPresence of elevated levels of SP,
CGRP and cytokines suggests that soft tissue pain mediated by a process of central sensitization and neurogenic inflammationDetermining the biochemical profile of
active MTrPs may help elucidate mechanisms of the initiation and amplification of soft tissue pain and target treatments at those mechanisms