common chronic pain syndromes across the lifespan how · pdf fileadequate scientific basis ......
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Common Chronic Pain Syndromes Across the Lifespan
Kim Dupree Jones PhD, FNP-BC, FAAN
How to Optimize Management without an
Adequate Scientific Basis
US Costs of Common Chronic Conditions
Continuum of Chronic Pain
C Maxwell & K Jones 2014
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The Clinical Expression of Chronic Pain is Widely Variable
Mild, fewer
symptoms and
easily controlled
Severe, treatment
resistant and very
complex
Need an Individually
Tailored Program of
Interdisciplinary
Management
Perrot & Russell, 2014, Eur J of Pain; Paiva & Jones, 2010, Best Practices Rsch Clin Rheum
Validation/Education/Goal Setting
Tramadol/Pregabalin/Duloxetine
Exercise Advice
Chronic Pain Conditions Have Overlapping Pain Pathophysiology
Common Pain Pathways
Facilitatory
Ascending• NMDA-glutamate• Substance P-NK-1• Nitric oxide
Inhibitory
Descending• Norepinephrine• Serotonin• GABA• Opioids
– Endorphins– Enkephalins
Descending Pain Pathway
Thalamus
Hypothalamus
Processing Perception
of Pain
SpinalCord
DorsalHorn
Muscle Tissue(periphery)
Nociceptor
BrainStem
RapheNuclei
Cortex
Periaqueductal gray (PAG)
Ascending Pain Pathway
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spine painpelvic painfunctional abdominal pain/irritable bowel irritable bladder TMDheadaches myofascial painfibromyalgia
If your patient has one of these chronic non-malignant pain disorders, they are ahead of the scientific curve
Chronic = Incurable
Managing provider expectation
and patient activation are key
to successful partnership
Dizziness
Irritable bowel
Irritable bladder
Autonomic dysfunction
Restless legs
Multiple sensitivities
HeadachesCognitive dysfunction
Depression / Anxiety
Paresthesia
Insomnia Jaw pain
Severe fatigue
Exercise intolerance
Chronic pain is rarely
single site or single
symptom
Carnes et. al, 2007, Rheumatology
Symptom Impact Questionnaire
Directions: For each of the following 10 questions, check the one box that best indicates the intensity of the following common symptoms over the last 7 days.
• Criteria:
Bennett RM, Friend R, Jones KD, (2009)The Revised Fibromyalgia Impact Questionnaire (FIQR): validation and psychometric properties. Arthritis Res Ther.On-line calculator available at http://www.fiqr.info/FIQR-CALC.htm
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Bennett RM, Friend R, Jones KD, Ward R, Han BK, Ross RL. The Revised Fibromyalgia Impact Questionnaire (FIQR): validation and psychometric properties. Arthritis Res Ther.2009;11(4):R120On-line calculator available at http://www.fiqr.info/FIQR-CALC.htm
Scores and Fibromyalgia Severity
Fibromyalgia Impact Questionnaire-Revised
Tying Medications to MechanismClass Mechanism Medication Pain Sleep Fatigue Mood
SNRI Increase concentration of Serotonin andNorepinephrine
Venlafaxine + + + ++
Milnacipran* + + ++ ++
Duloxetine* + + + ++
TCA Increase concentration of Serotonin andNorepinephrine
Amitriptyline + ++
Cycolbenzaprine + ++
Nortriptyline + +
SSRI Increase concentration of Serotonin
Fluoxetine ++
Paroxetine ++
Other NE and Dopamine Buproprion + ++ ++
Anti-epileptic
Decrease release of excitatory neurotransmitters
GabapentinPregablin*
+ + + +
Analgesic NE & 5HT, weak mu agonist Tramadol ++ + +
Sodium Oxybate
Gaba, CNS depressant Xyrem ++ ++ + +
NSAIDs
Non-steroidal anti-inflammatory drugs constitute the number one class of agents used to treat fibromyalgia1
No evidence of effectiveness as monotherapy for fibromyalgia– May be modestly helpful combined with a tricyclic antidepressant2
“Since fibromyalgia is not an inflammatory disease, it is not surprising we have a lot of treatment failures”3
Chronic analgesic use can set up cycle of rebound headaches, complicating fibromyalgia management4
Useful for inflammatory comorbidities??
1. Clauw DJ. J Clin Rheumatol. 2007;13:102-109.
2. Goldenberg DL, et al. Arthritis Rheum. 1986;29:1371-1377.
3. Griffing GT. Medscape J Med. 2008;10(2):47.
4. Chakrabarty S, Zoorob R. Am Fam Physician. 2007;76:247-254.
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Tramadol
Tramadol has some mu-opioid and SNRI activity:
– Efficacious, for patients not on opioids
• Number one agent recommended by consensus statement from EULAR, 20082
Not a controlled substance Available short acting and long acting
– Nausea better tolerated in fixed-dose combination with acetaminophen3
– Limiting side effect is nausea (Zantac), +/- skin rash3
– Risk of serotonin syndrome when combined with SSRIs/ SNRIs and triptans; seizures in patients using neuroleptics, or other drugs that decrease seizure threshold4
2. Chu LF, et al. Clin J Pain. 2008;24:479-496.3. Bennett RM, et al. Am J Med. 2003;114:537-545.
4. Goldenberg DL. Best Pract Res Clin Rheumatol. 2007;21:499-511.
Tramadol/APAP
– Each tablet contains:
• 37.5 mg tramadol*
• 325 mg acetaminophen
– Not scheduled
– Not an NSAID or COX-2 NSAID
– Current indication is short-term management of pain (5 days)
– Do not use with history of seizure disorder
* 25% less tramadol
Opiates
Limited, randomized, controlled clinical trials1
Opiates may heighten pain sensitivity (opioid-induced hyperalgesia)2
Opiates may be associated with cognitive dysfunction, constipation, dose escalation and tolerance; addiction and diversion rare in FM
– Yet, #1 medication ranked by nearly 3000 FM patients in survey 3
– American Pain Society recommends long acting, compared to short acting medications for many chronic pain states
– Consider using non-narcotic, adjunctive medications to reduce the total opioid dose
– As better therapies emerge, opiate use will decline
1. Clauw DJ. J Clin Rheumatol. 2007;13:102-109.2. Chu LF, et al. Clin J Pain. 2008;24:479-496.
3. Bennett, RM. BMC Rheum. 2007.
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Opioid Withdrawal Protocol
Meds to relieve withdrawal symptoms
� Analgesic: tramadol, pregabalin– Clonidine relieves autonomic symptoms
– Benadryl , Unisom or Trazadone to relieve insomnia
– Dicyclomine for abdominal cramps
– Zofran or phenergan for nausea
– Imodium for diarrhea
Antiepileptics (Alpha-2-Delta Ligands):Pregabalin and Gabapentin
Mechanism:– Bind to α2δ subunit of voltage-gated calcium channels– Reduce calcium influx and inhibit release of neurotransmitters (eg,
glutamate, substance P)– Hypothesized to work on ascending pain pathways
Indications:– Postherpetic neuralgia (both agents)– Adjunctive therapy for partial onset seizures (both agents)– Pain associated with diabetic peripheral neuropathy (pregabalin)– Fibromyalgia (pregabalin)
Crofford LJ, et al. Arthritis Rheum. 2005;52:1264-1273.
Pregabalin 14-Week Fixed-Dose FM Trial: Significant Improvement in Pain
*600 mg/day of pregabalin is not an approved dose fo r FM; †P<0.01; ‡P≤.0125.End point mean pain score based on modified baseline observation carried forward approach (BOCF). Baseline mean = 6.7 (moderate to severe pain). P value–based LS means using MMRM ANCOVA.
Scored 0-10, lower score represents improvement. Arnold et al. APS 2007; Data on file. Pfizer Inc, New York, NY.
††
IMP
RO
VE
ME
NT
LS m
ean
chan
ge fr
om b
asel
ine
Week
-3
-2
-1
0
0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 EP
††
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Placebo (n=184)Pregabalin 300 mg (n=183)Pregabalin 450 mg (n=190)Pregabalin 600 mg (n=188) *
‡‡‡
†† †
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Effect of Duloxetine on AveragePain Score: ≥30% Improvement
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% o
f Pat
ient
s
Russell IJ, et al. J Musculoskel Pain. 2007;15(suppl 13):58. Abstract 103.
*†
*P≤0.05 vs placebo. †P≤0.01 vs placebo.
50.7 47.252.1 49.3
36.0 37.4
0
10
20
30
40
50
60
3 Month 6 Month
Duloxetine 60 mg/dDuloxetine 120 mg/dPlacebo
Effect of Milnacipran onComposite Response : ≥30% Improvement
Pain End Points
*† †
*
% o
f Pat
ient
s
3 Months 6 Months
*P<0.05 vs placebo. †P<0.001 vs placebo1. Clauw DJ, et al. Clin Ther, 2008;30(11) 1988-2004.2. Mease PF et al. J Rheumatol 2009;36(2):398-409.
45% 44%45% 45%
27% 28%
01020304050
Milnacipran 100 mg/dMilnacipran 200 mg/dPlacebo
Antidepressants for Chronic Pain:Which To Choose?
Most studies using antidepressants as analgesics for chronic pain demonstrate effects on pain that are distinct from effects on mood1
Tricyclic antidepressants– Block reuptake of serotonin and/or norepinephrine– Low doses may effectively treat pain, poor sleep, fatigue2
– Tolerability issues; initiate therapy at very low doses, then titrate slowly1
Selective serotonin reuptake inhibitors– Better side-effect profile than TCAs– Used at higher doses, the older, less-selective SSRIs are generally more efficacious
than “highly selective” agents1,3
Dual receptor inhibitors– Inhibit both serotonin and norepinephrine– Unlike TCAs, generally no significant activity at other receptors; better tolerability1
– May have better analgesic effect than pure serotonergic drugs1
Two SNRIs have undergone multicenter trials in fibromyalgia: duloxetine and milnacipran (both FDA-approved therapies)
1. Clauw DJ. J Clin Rheumatol. 2007;13:102-109; 2. Arnold LM, et al. Psychosomatics.2000;41:104-113; 3. Fishbain D. Ann Med. 2000;32:305-316.
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Spaeth & Bennett, 2012, Ann Rheum Dis
Painp= 0.002 or <0.001
Fatiguep=<0.001
Jenkins sleep: 16 to 11, p<0.001
4 lb wt loss
71% met PGIC goal
1 year continuation:
Responder analyses showed that 68.8% of patients achieved ≥ 30% reduction in pain VAS and 69.7% achieved ≥ 30% reduction in FIQ total score at study endpoint
Arth Rsch Ther 2013
Marijuana / Marijuana Derivatives
Add text here
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Summary Of Evidence For Efficacy Of Pharmacologic Therapies
1Clauw DJ. J Clin Psychiatry. 2008;69(suppl 2):25-29. 2Chakrabarty S and Zoorob R. Am Fam Physician. 2007;76:247-254.3Goldenberg DL, et al. JAMA. 2004;292:2388-2395. 4Russell IJ, et al. Arthritis Rheum. 2009;60:299-309. 5Staud R. Drugs. 2010;70:1-14.
Currently FDA-approved for FM 5: duloxetine; milnacipran; pregabalin
Strong Evidence• α2δ ligands
(pregabalin, gabapentin)1
• Dual reuptake inhibitors (SNRIs, duloxetine, milnacipran)1
• Tricyclics and related agents (amitriptyline, cyclobenzaprine)1-3
• Sodium oxybate4
Moderate Evidence• SSRIs (fluoxetine ±
amitriptyline, paroxetine)1-3
• Tramadol ±acetaminophen1-3
• Pramipexole1
Weak/No Evidence• Nonsteroidal anti-
inflammatory drugs1-3
• Opioids1-3
• Corticosteroids2,3
• Benzodiazepines1,3
• Phenteramine• Pindolol• Amantadine• Namenda
Can’t treat Overall Pain? Treat a Pain Generator: Migraine Preventatives
More than 2 migraines per week or more than two migraine headache days per week
1. Propanolol* 60mg SR (NOT short acting) one to three a day
2. Amitriptiline 25mg q hs and increase to at least 75mg q hs
3. Zonegran 100-200mg bid
4. Long acting NSAIDS
5. Consider posture and trigger point therapy
*Class A Evidence
Migraine Abortives
• Imitrex 50 or 100mg, Maxalt MLT, Frova* 2.5mg to be taken right at onset and again two hours later (no more than two in 24 hours)
• Can pair with Naproxen 500mg or other shorter acting anti inflammatory, caffeine or tylenol for very effective non narcotic therapy
• Zofran for nausea
• Benedryl 25mg, Tramadol 50mg can also be added
* Class A Evidence
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Treat Regional Pain Sources
Myofascial Trigger Points:
exercise
self-care
Injection/dry needling
massage
myofascial release
Myofascial Trigger Points
It is important to eliminate myofascial
trigger points
Myofascial “Web”
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Castro-Sanchez et al . 2011
� 20 weeks myofascial release therapy
� Compared to sham ultrasound
� Significant improvement in pain and tender
points
� Pain reduction persisted at 1 and 6 months post-
intervention
25th Anniversary of Exercise Interventions in Fibromyalgia
> 135 original studies
> 6,200 subjects
6 + systematic reviews
4 notable narrative reviews
Busch et al., 2009, Int J of Clin Rhem & Busch et al., 2010, Curr Pain Headche Rep
What Improves in Fibromyalgia During Land-based Aerobic Trials?
Physical function/fitness
effect size=0.65 (sustained at follow up)
What doesn’t improve?
Sleep effect size=0.01 NS (NS at follow up)
What isn’t sustained?
Pain effect size=0.31 (0.13 NS at follow up)
Hauser, 2010, Arthritis Rsch & Ther
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Mindful movement interventions:
What is Emerging in FM for Pain & Sleep?
Tai chi (land or water)
QigongYoga w/ mindfulness
Mist , Firestone & Jones, 2013,J of Pain Rsch
Mindful Movement Hypothesis
Mindfulness entails meditation and other strategies for developing greater:
• Presence of mind in the present moment, acting with awareness
• Non-judgement / non-reactivity of symptoms
• Acceptance / willingness to learn from pain and other challenging experiences
When exercise is combined with mindfulness, can patients learn to move mindfully and better accept disagreeable sensations arising during movement? Moreover does improved acceptance modulate pain by psycho-physiological mechanisms such as activation of the PAG?
The raisins sitting in my sweaty palm are getting stickier by the minute. They don't look particularly appealing, but when instructed by my teacher, I take one in my fingers and examine it.
Time Magazine, February 2, 2014
The ability to focus for a few minutes on a single raisin isn't silly if the skills it requires are the keys to surviving and succeeding in the 21st century
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Conclusion: Eight weeks of daily yogic meditation reversed the pattern of increased expression of genes associated with inflammation
Science Meets Meditation
Epigenetics:Changes in gene
expression related to environmental
factors
State of Published Evidence in FM
�Meditation
�Mostly focuses on mindfulness (6 MBSR studies)
�Improves quality of life, mood
�Mixed results in symptom severity but generally not pain reduction
�Mind + Body Movement is different exercise or meditation alone
1 Mist SD, Firestone KA, Jones KD 2013
Cognitive Behavioral Therapy: Meta analysis
• Reduced depressed mood; small effect (p=0.004)
• Improved pain self efficacy; large effect (p=0.003)
• Operant behavioral therapy reduced the number of physician visits; large effect (p<0.001)
• No significant effect on pain (p=0.28), fatigue (p=0.61), sleep (p=0.50), health related quality of life (p=0.37)
• iPhone app
(Bernardy, et al., 2010, J Rheumatology)
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Acupuncture
AcupunctureA 5000-year old medical system based on the theory that “Qi” (the life force which flows throughout our body) is out of balance
Deare, JC, et al. Acupuncture for treating fibromyalgia. Cochrane database review. 2013, May 31
1. There is low to moderate-level evidence that acup uncture improves pain and stiffness
2. The effect lasts up to one month
Reviewed 9 randomized controlled studies (i.e. sham acupuncture) involving 321 subjects:
Cochrane Database Review 2013
3. Electro acupuncture is probably more effective th an manual acupuncture
4. The effect of acupuncture does not consistently d iffer from sham acupuncture in reducing pain or fatigue
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International Perspective
Great Britain, Germany, Canada and Israel all include acupuncture among the highest level of evidence and suggest it be used depending on the individual’s interest.
State of Published Evidence: Herbal
Medicine
� Huge field with very little research
� Several Chinese medicine formulas have been evaluat ed but study quality is low and none have been replica ted
� Topical capsaicin has been shown to improve sleepdisturbances and tenderness but not pain.
State of the Current Evidence: Diet
�Generally poor evidence in chronic pain due to lack of studies
�Five studies of fibromyalgia patients without additional diseases
�Holton, et al at OHSU found that MSG worsened fibromyalgia severity in patients with FM & IBS
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Raw Foods Diet
Kindler, L.L., Jones, K.D., & Holton, K. (2012). Potential dietary links for central sensitization in fibromyalgia: past reports, future directions. Clinical Rheumatology
Optimal Nutrition
• Nutrition is argued to be the single most important factor in optimizing your patient’s health
• Positive vs. negative aspects to diet:
• Positive� Vitamins, Minerals, Protein, EFAs, Fiber
• Negative� Food additives, excess sugar, pesticides, herbicides,
trans fats
Food Additives
• Excitotoxins
� Glutamate, aspartate and L-cysteine
� Found under a myriad of names
• Artificial sweeteners
� Aspartame, acesulfame K, saccharin, sucralose
Artificial colors
� Interactions w/excitotoxins
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Glutamate
• Glutamate – a non-essential, negatively charged AA from diet
• The most ubiquitous excitatory neurotransmitter in mammals
– Functions all over body (gut, immune system, pancreas, neuromuscular junction and brain)
– Precursor to the inhibitory neurotransmitter GABA
• Disordered glutamatergic neurotransmission has been implicated in chronic pain
• Excess glutamate can lead to excitotoxicity
• Bound vs free glutamate
– Meat versus soy sauce
Food Additives
Gelatin
Focus on REAL Food
• Real Food – Food that is not highly processed
� Low in additives, no trans fats
� High in nutrients
� High in fiber
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What Nutritional Factors are Important for Optimal Glutamatergic Function?
� Adequate protein and low sugar
� Antioxidants - Vitamins C & E
� Vitamin D
� Omega-3 Fatty Acids
� Magnesium
� Zinc
Hidden ExcitotoxinsAcesulfame-K (Sunett, Sweet One)Aspartame (Equal, NutraSweet, Canderel)Autolyzed yeast (or autolyzed yeast extract)Barley malt extractBouillonBrothCalcium caseinateCarrageenanFlavoringGelatinHydrolyzed corn, wheat, or soy protein L-cysteineMalt extractMalt flavoringModified food starch (any type)Monopotassium glutamateMonosodium glutamate (MSG)
Natural flavoringNutritional yeastPlant protein extract Saccharin (Sweet ’N Low)SeasoningSmoke flavoringSodium benzoateSodium caseinateSodium guanylateSodium inosinateSoy (soybean oil /soy lecithin are OK to eat)Soy protein concentrateSoy protein isolateSpices (this term can hide other ingredients)StockSucralose (Splenda)Textured proteinWhey protein concentrateWhey protein isolateYeast extract
Too Confusing?:
Fooducate iPhone app
Complementary & Alternative Evidence
Langhorst et al. (2012) Complementary and alternative therapies for fibromyalgia syndrome. Systematic review, meta-analysis and guideline. Schmerz, 26(3):311-7.
Qigong, Tai Chi, Yoga w/mindfulness - Strong evidenc e
Hydrotherapy - Strong evidence
Acupuncture – mixed evidence
Manual Therapies- mixed evidence
Relaxation, Biofeedback, Mindfulness – mixed evidenc e
Herbs, nutraceuticals, reiki, homeopathy – not recom mended
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Summary: Practice Points
Chronic pain is common and characterized by:
– Widespread pain in peripheral tissues
– Psychological distress (at least initially)
– Central sensitization
– Physical Deconditioning
Pain component is consequence of disordered neurophysiology:
– Patients perceive more pain from non-painful stimuli than do healthy controls and experience greater pain from painful stimuli
Rationale for treatment involves 4 important strategies:
– Reduction of peripheral nociceptive input
– Improvement or prevention of central sensitization
– Treatment of pain-related negative affect
– Enlisting the patient as a partner (education, exercise, diet, CBT)
Jones, K.D. & Paiva, E. (2011) Developing an inter disciplinary fibromyalgia clinical practice.Best Practices Rheum.
The EndQ & A