1. health and fitness
2. disease
3. chronic pain

Complex Regional Pain
Syndrome: updates on treatment
Reflex Sympathetic Dystrophy
Pradeep Chopra, MD
Assistant Professor (Clinical) Brown Medical School
Director, Pain Management Center, RI
Copyright © 2013 by Pradeep Chopra. No part of this presentation may be
reproduced or transmitted in any form or by any means without written permission of
the author
1
Disclosure and disclaimer
• I have no actual or potential conflict of
interest in relation to this presentation or
program
• This presentation will discuss “off-label”
uses of medications
• No financial interest in any pharmaceutical
company or otherwise
• Please discuss with your physician before
making any changes
Copyright © 2013 by Pradeep Chopra. No part of this presentation may be reproduced or transmitted in 2
any form or by any means without written permission of the author
Introduction
• Training and Fellowship, Harvard Medical
school
• Pain Medicine specialist
• Assistant Professor – Brown Medical
School, Rhode Island
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What is CRPS / RSD
• Complex Regional Pain Syndrome formerly
Reflex Sympathetic Dystrophy
• Syndrome characterized by a continuing
pain that is disproportionate to the usual
course of any trauma or lesion.
• Usually starts after a trauma,
immobilization. Maybe spontaneous or
after a stroke.
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How common is RSD?
• Not sure – because there are a lot of cases
that are undiagnosed and misdiagnosed.
•
• USA: estimated to be 50,000 new cases
per year
• New cases of Parkinson's every year:
60,000
1 Andreas Kopf, Patel N, IASP 2010
2 DeMos M, de Bruijn AG, et al 2006
3 Van Den Eeden, Tanner, et al 2003
Deussing, Jankosky 2012
Marinus J, Moseley GL et al 2011
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Signs and Symptoms of CRPS 1
• Pain starts in one limb but can present in the
trunk (spine, abdomen, perineum)
• Constant pain, even at rest with intermittent
exacerbations. Unexplained and diffuse
• Severe pain - burning, tearing, shooting
• Temperature, color change.
• Edema
• Area of pain larger than the primary injury
• Limited range of motion
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Signs and Symptoms of CRPS
2
• Cannot be explained by any other medical
condition
• Allodynia - pain on light touch
• Hyperalgesia - increased pain to mildly
painful stimulus
• Trophic changes - nail growth changes
(faster, distorted), hair growth changes
(coarser, darker, rapid growth, hair falling),
skin changes (atrophy of skin), skin lesions
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Color, temperature and swelling
94
°
88
°
Swelling
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Nail changes, swelling
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Coarser, darker, faster hair
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Chest Pain in CRPS
• Atypical chest pain i.e. chest pain not due
to cardiac causes
• In CRPS, it presents as above the breast,
radiates to the jaw, face, shoulder and arm
• Can be reproduced by raising the arm,
pressure over certain parts of the chest
• Cause: Irritation and sensitization of the
Inter-costo-brachial nerve (ICBN).
Atypical Chest Pain: Evidence of Intercostobrachial Nerve Sensitization in Complex Regional Pain
Syndrome Jennifer W. Rasmussen, MD, John R. Grothusen, PhD, Andrea L. Rosso, MPH,and Robert
15
J. Schwartzman, MD: Pain Physician 2009; 12:E329-E334 • ISSN 2150-1149
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Best Diagnostic tool
• A good history and physical examination
• A repeat examination should be done to
come to a diagnosis because of the
fleeting nature of some of the symptoms
(color change, temperature asymmetry
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Tests that are not helpful for diagnosing
RSD
• Imaging techniques – x-ray, MRI, fMRI, Three
phase bone scan, bone density
• Blood tests
• Skin biopsy
• Sympathetic nerve tests – sweat test,
sympathetic skin response,
• Nerve tests – EMG, nerve conduction,
• The tests MAYBE used if another diagnosis is
suspected.
Atkins RM, Tindale W, Bickerstaff D, Kanis JA. Quantitative bone scintigraphy in reflex sympathetic dystrophy. Br J
Rheumatol 1993;32(1):41-5.
Todorovic-Tirnanic M, Obradovic V, Han R, Goldner B, Stankovic D, Sekulic D, et al. Diagnostic approach to reflex
sympathetic dystrophy after fracture: radiography or bone scintigraphy? Eur J Nucl Med
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CENTRAL SENSITIZATION
What really happens in CRPS
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Central Nervous system
• The Central Nervous system is made up of
2 types of cells – Nerve cells and Glia
20
Glia
1
• Glia constitute 70% to 80% of all cells in
the Central Nervous system (CNS)
• Under normal conditions are part of the
immune system
• Glia when activated release inflammatory
chemicals
Watkins, Hutchinson, Ledeboer, Milligan et al Brain Behav
Immun 2007 Feb; 21(2): 131-146
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Glia and nerves under normal conditions
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Activated Glia
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Chemicals released by activated Glia
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Nerve inflammation - Central Sensitization
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The problem is no longer in the nerves. Its in the cells (Glia
cells)
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NMDA Receptors
• In CRPS the Central Nervous system is
flooded with pain
• This results in activation of the NMDA
receptors
• Ketamine and other drugs block NMDA
receptors
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NMDA receptors
• In CRPS, NMDA receptors proliferate,
leading to increased pain
• Ketamine blocks NMDA receptors
...........but not forever
• It blocks it long enough to reset the
nervous system and for other modalities to
work
31
Management
Complex Regional Pain Syndrome
(CRPS)
Reflex Sympathetic Dystrophy (RSD)
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Basic guidelines in treating RSD
• Start treatment immediately, even if you
suspect RSD
• Treatment should be directed towards
restoration of function (focus away from
pain)
• Multidisciplinary approach
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Starting treatment medicines and exercise
• Start low, go slow
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Ketamine for CRPS
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Ketamine
•
•
•
•
•
•
Strong NMDA Receptor blocker
One of the safest anesthetic drugs
Powerful analgesic
CRPS - activation of NMDA receptors
Effect unreliable when taken orally.
Effective as IV or submucosal (Troche)
Correll GE, Maleki J, Gracely EJ, Muir JJ, Harbut RE. Subanesthestic ketamine infusion therapy: a
retrospective analysis of a novel therapeutic approach to complex regional pain syndrome. Pain Medicine
2004;5(3):263-75.
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Ketamine in RSD
• Administered in sub-anesthetic doses – blocks
NMDA receptors without causing too many side
effects
• In RSD it decreases Central Sensitization
• Rough estimates – 85% show improvement in
daily activities, reduction in their medications
and improved lifestyles
• It is not a cure. It is to be done along with
other therapies
Correll GE, Maleki J, Gracely EJ, Muir JJ, Harbut RE. Subanesthestic ketamine
infusion therapy: a retrospective analysis of a novel therapeutic approach to
complex regional pain syndrome. Pain Medicine 2004;5(3):263-75.
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Ketamine – out patient
•
•
•
•
•
•
•
Increasing dose of ketamine over 10 days
Start at a low dose, increase everyday
Usually start to see some relief by day 4 or 5
If no relief by day 5, stop
Infusion done over 4 to 5 hours
Full standard monitoring
Qualified personnel must be present at all
times
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Continuous infusion protocol
• Done in an Intensive Care Unit
• A continuous 24 hour infusion done over
five to six days
• Usually used only for the loading dose.
• Follow up booster infusions after discharge
may be done as an outpatient procedure
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IV Ketamine - boosters
• Very important part of the treatment protocol
• As the effect of the initial ketamine wears off,
the glial cells begin to activated again.
• Boosters may be done after 2 weeks for 2 days
• Then, for one day every 4 to 8 weeks
depending on the severity, chronicity and
response
• Sometimes, it may be necessary to do a 2 day
booster.
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Ketamine infusions
• Must be done under ASA (American
Society of Anesthesiologists) standard
monitoring
• Continuous oxygen levels, heart rate, EKG
• Intermittent (every 15 minutes) blood
pressure, conscious level
• Very quiet room
• Dark room
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Ketamine infusions
• Avoid talking, television, music, etc
• Avoid any visual and sound stimulation
• Dreams, hallucinations – to a mild degree
imply effective dose.
• Hallucinations triggered by loud sounds
and light
• Rest of the day – avoid loud traffic, spend
the day at home in a quiet, dark room
• Take a benzodiazepine pill after infusion
43
Ketamine infusions and opioids
• No interaction
• Opioids increase sensitization to pain in
CRPS, whereas
• Ketamine decreases sensitization CRPS
• Best to come off all opioids before
undergoing ketamine infusion
• May use the beneficial effects of Ketamine
to control pain as tapering off opioids
44
Ketamine side effects
• Most of the side effects are temporary and
short lived and reversible.
• We do not know of any long term side
effects of ketamine infusions.
• Nausea, vomiting, colorful dreams,
hallucinations, headache
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Ketamine Troche
• Only for acute flare up. Not for regular use.
• Take 10mg in your cheek or under tongue
every 1 hour till relief or for a total of 50mg
10mg ___1 hour___10 mg___1 hour____10mg _____1 hour_____10mg
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Which Protocol is best ?
How much ketamine is enough?
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Factors that are important in getting the best out of a ketamine
infusion
• How long does the ketamine stay in the body
i.e. how long are the receptors blocked
• How much is needed to keep the ketamine in
the body / keep the receptors blocked
• Minimize trauma while delivering the infusion
• Ketamine infusions are good only if done in
conjunction with other therapies, especially
exercise
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Low Dose Naltrexone
LDN
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Low Dose Naltrexone (LDN) 1
•
•
•
•
Competitive antagonist of opioid receptors
Clinically used for 30 years for addiction
Suppresses the effect on the glia, which….
…decreases the release of inflammatory
chemicals
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Low Dose Naltrexone (LDN)
• Very different from
buprenorphine/naloxone (Suboxone™)
• Buprenorphine is a narcotic
• Naloxone and naltrexone are in the same
family
• The naloxone or naltrexone is for
prevention of abuse and has no beneficial
affect
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Low Dose Naltrexone (LDN)
2
• There are several theories as to how LDN may work.
1. Transiently blocks opioid receptor leading to positive
feedback production of endorphins (Zagnon)
2. LDN increases production of OGF (opioid growth
factor) as well as number of and density of OGF
receptors by intermittently blocking the opiate
receptor. Increased in OGF repairs tissue and healing.
1. Effect not mediated by opioid receptor activity.
Potentially mediated by activity on Toll Like Receptors
4 (TLR4)
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Low Dose Naltrexone (LDN) 3
• Dose can vary anywhere between 1.75mg
to 4.5mg
• May cause insomnia, mild headaches
initially.
• Patients report increased physical activity,
flare ups not as acute, better tolerance to
pain.
• To avoid all opioids or tramadol.
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Case of RSD treated with LDN
RSD with dystonia
before LDN
RSD after LDN
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Severe RSD with skin lesions
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IV ketamine and LDN
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LDN and CRPS
Chopra, Li, Unpublished data from retrospective review, 2013 – under review
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Muscle symptoms in CRPS
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Muscle symptoms in CRPS
•
•
•
•
Muscle spasms
Dystonia
Tremors
Myoclonus
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Muscle spasms
•
•
•
•
•
Magnesium
Diazepam (Valium®), Clonazepam
Flexeril
Tizanidine
Baclofen
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Muscle Relaxants
• Cyclobenzaprine, tizanidine
• Not very helpful for muscle symptoms of
RSD
• Baclofen and diazepam or clonazepam
may have some benefit
• Intrathecal (spinal pump) baclofen is not
helpful
Schwartzman RJ, Kerrigan J. The movement disorder of reflex sympathetic dystrophy. Neurology
1990;40(1):57-61.
Bhatia KP, Bhatt MH, Marsden CD. The causalgia-dystonia syndrome. Brain 1993;116 (Pt 4):843-51.
Hilten JJ van, Beek WJ van de, Vein AA, Dijk JG van, Middelkoop HA. Clinical aspects of multifocal or
generalized tonic dystonia in reflex sympathetic dystrophy. Neurology 2001;56(12):1762-5.
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Magnesium
• IV magnesium: small study with 8 patients,
administered IV magnesium over 5 days,
for 4 hours each day.
• Significant decrease in pain
• Improvement in quality of life
Collins et al., Pain Medicine, 2009, 10:930-940
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Magnesium
• Magnesium down regulates NMDA receptor
(responsible for CRPS)
• Study done with IV magnesium was very
positive for helping CRPS
• Magnesium has been used to treat migraines
• Blood tests for Magnesium levels are not
accurate
• Best to use Chelated Magnesium
Collins, S, Zuurmond WW et al. Intravenous Magnsium for Complex Regional Pain Syndrome Type I (CRPS I) patients: A
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Pilot study. Pain Medicine Vol 10, Number 5. 2009
Tadalafil (Cialis) for CRPS
• Treatment of cold CRPS resulted in
significant reduction of temperature
difference between affected and unaffected
limbs
• Long term effect unknown
Groeneweg et al., BMC Musckoskeletal Disorders, 2008, 9:143
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FREE RADICAL
SCAVENGERS
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Free Radicals – what are they?
2
• When molecules break up, some electrons are
left free to float around.
• These unbalanced molecules are called free
radicals
• These unbalanced molecules become very
unstable and attack another molecule or
electron to grab onto for stability.
• In our body, when these unstable electrons
attack other molecules to achieve stability they
damage human cells – nerves, muscles
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Free Radicals attack and rob energy from other cells to satisfy
themselves
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Free Radical scavengers (Antioxidants)
•
•
•
•
Alpha Lipoic Acid
Vitamin C
DMSO (Dimethyl sulphoxide)
N-Acetyl Cysteine (NAC)
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DMSO 50% - Dimethyl Sulphoxide
• Topical use only.
• Particularly helpful for ‘warm’ CRPS
• CRPS less than 1 year - three month
course of DMSO applied 5 times topically
every day
• CRPS more than 1 year – One month trial
course of DMSO everyday.
• If trial helps, then continue
Geertzen JH, Bruijn H de, Bruijn-Kofman AT, Arendzen JH. Reflex sympathetic dystrophy: early treatment and
psychological aspects. Arch Phys Med Rehabil 1994;75(4):442-6.
Zuurmond WW, Langendijk PN, Bezemer PD, Brink HE, Lange JJ de, Loenen AC van. Treatment of acute reflex
sympathetic dystrophy with DMSO 50% in a fatty cream. Acta Anaesthesiol Scand 1996;40(3):364-7.
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N- Acetyl Cysteine
• Useful for cold allodynia
• N-Acetylcysteine 600mg three times a day
for three months
• Other uses: acetaminophen overdose,
mucolytic
• Gastric irritant – take after food
Perez RS, Zuurmond WW, Bezemer PD, Kuik DJ, Loenen AC van, Lange JJ de, et al. The treatment of complex regional pain
syndrome type I with free radical scavengers: a randomized controlled study. Pain 2003;102(3):297-307
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Vitamin C
• Natural antioxidant
• There are several studies that have shown that
Vitamin C can prevent CRPS after a fracture
• Recommended daily allowance of Vitamin C is
60mg (National Research Council, USA).
• Vitamin C 500 mg for 45 days to 50 days was
shown to prevent development of CRPS
• ? Any value to using it in established CRPS,
certainly helpful in prevention
Zollinger Paul, Tuinebereijer, Keir R, Breederveld, 1999, Lancet
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Alpha Lipoic acid (ALA)
1
• Free Radical scavenger
• Promising results in diabetic neuropathy
and other polyneuropathies
• No trials in CRPS
• Has been approved in Germany for
treating neuropathic pain
Kapoor S, Foot Ankle Spec, 2012 Aug;5(4); 228-9
Snedecor SJ, Sudarshan L, Cappelleru JC etc al. 2013 Pain Pract,
Mar 28
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Alpha Lipoic acid (ALA)
2
• Its also helps with autonomic neuropathy
(common in CRPS) POTS, Dysautonomia
• Effective when taken as IV (Intravenous)
• May be taken orally
• Dose: 600mg to 1200mg per day
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Alpha Lipoic Acid (ALA)
• Naturally produced in the body
• Spinach, red meat, potatoes, broccoli,
yams, carrots, beets, yeast
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Ibudiblast
• Promising research in helping CRPS
• Works by deactivating glia
• Currently available in Japan for asthma
and stroke.
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Clonidine
• Alpha2 adrenerigic agonist – prevent
release of catecholamines by a presynaptic action
• Transdermal more effective than oral
• Effective for hyperalgesia and allodynia
(Davis et al)
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Bones, joints in CRPS
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Osteopenia / Osteoporosis
•
•
•
•
•
•
•
Thinning of the bone is a feature of CRPS
Prevention is the best way to treat it
Use the limb as much as you can
Do weight loading exercises
Legs – do weight bearing exercises
Arms – lift weights, push against a wall
Clordronate and alendronate
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Bisphosphonates
•
•
•
•
Group of drugs to treat osteoporosis
Clodronate IV
Alendronate IV
Helpful for treating CRPS
Forouzanfar T, Koke AJ, Kleef M van, Weber WE. Treatment of
complex regional pain syndrome type I. Eur J Pain 2002;6(2):105-22.
Adami S, Fossaluzza V, Gatti D, Fracassi E, Braga V. Bisphosphonate
therapy of reflex sympathetic dystrophy syndrome. Ann Rheum Dis
1997;56(3):201-4.
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Calcium regulating drugs – in refractory
cases
• Clodronate (300mg) daily IV – pain,
swelling, movement range in acute CRPS
• Alendronate (7.5mg) daily IV - pain,
swelling, movement range in acute CRPS
• Use in refractory cases
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Calcitonin
•
•
•
•
Hormone produced by the thyroid gland
Helps with pain and calcium regulation
Taken by nose (better) and injection
Research with mixed results – some
effective and some, not as much
Kingery WS. A critical review of controlled clinical trials for peripheral neuropathic pain and complex regional pain syndromes. Pain
1997;73(2):23-39.
Berg P van den, Bierma-Zeinstra S, Koes B. Therapie bij sympathische reflexdystrofie. Huisarts Wet 2002;45:166-71.
Perez RS, Kwakkel G, Zuurmond WW, Lange JJ de. Treatment of reflex sympathetic dystrophy (CRPS type I): a research synthesis of
21 randomized clinical trials. J Pain Symptom Manage
2001;21(6):511-26.
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Forouzanfar T, Koke AJ, Kleef M van, Weber WE. Treatment of complex regional pain syndrome type I. Eur J Pain 2002;6(2):105-22.
Opioids
•
•
•
•
No long term studies
Counterproductive for CRPS
Activate glia
Increased Central Sensitization
Watkins, L, Hutchinson, Rice KC, Maier, 2009
Harke H, Gretenkort P, Ladleif HU, Rahman S, Harke O. The response of neuropathic pain and pain in complex regional
pain syndrome I to carbamazepine and sustained-release morphine in patients
pretreated with spinal cord stimulation: a double-blinded randomized study. Anesth Analg 2001;92(2):488-95.
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Prevalence of Misuse, Abuse, and Addiction
Misuse 40%
Abuse:20%
Total Pain
Population
Addiction: 2% to 5%
Webster LR, Webster RM. Pain Med. 2005;6(6):432-442.
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Gabapentin and pregabalin
• May help some patients with CRPS
• Gabapentin –Slow acting drug.
• Pregabalin – no evidence that it helps CRPS
but a trial course may be tried
• If there is no difference in 8 weeks, taper it off.
Serpell MG. Gabapentin in neuropathic pain syndromes: a randomised, double-blind, placebo-controlled trial. Pain
2002;99(3):557-66.
Vusse AC van de, Stomp-van den Berg SG, Kessels AH, Weber WE. Randomised controlled trial of gabapentin in
Complex Regional Pain Syndrome type I [ISRCTN84121379]. BMC Neurol 2004;4(1):13.
91
Hyperbaric Oxygen
• No good evidence that it helps in the long
term
• Anecdotal reports (mostly from hyperbaric
centers)
Kiralp MZ, Yildiz S, Vural D, Keskin I, Ay H, Dursun H. J Int Med Res. 2004 May-Jun;32(3):25862. Effectiveness of hyperbaric oxygen therapy in the treatment of complex regional pain
syndrome
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Sympathetic Nerve blocks
• Stellate ganglion blocks for upper extremity
• Lumbar sympathetic blocks for lower
extremity
• No good data on long term efficacy of
these blocks
• No diagnostic or therapeutic value
• Temporary at best
Price DD, Long S, Wilsey B, Rafii A. Analysis of peak magnitude and duration of analgesia produced by local anesthetics
injected into sympathetic ganglia of complex regional pain syndrome patients. Clin J Pain 1998;14(3):216-26.
Azad SC, Beyer A, Romer AW, Galle-Rod A, Peter K, Schops P. Continuous axillary brachial plexus analgesia with low dose
morphine in patients with complex regional pain syndromes. Eur J Anaesthesiol
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2000;17(3):185-8.
Antidepressants
• Tricyclic antidepressants (TCA) well
studied in neuropathic pain, not CRPS
• Reuptake blockers of serotonin and
noradrenaline (Amitrityline, nortriptyline) –
work well
• Selective noradrenaline blockers
(desipramine)
• SSRI (Prozac®, Zoloft®)– do not work well
Watson CP, Chipman M, Reed K, Evans RJ, Birkett N. Amitriptyline versus maprotiline in postherpetic
neuralgia: a randomized, double-blind, crossover trial. Pain 1992;48(1):29-36.
Raja SN, Haythornthwaite JA, Pappagallo M, Clark MR, Travison TG, Sabeen S, et al. Opioids versus
antidepressants in postherpetic neuralgia: a randomized, placebo-controlled trial. Neurology 2002;59(7):1015-
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Antidepressants ( SNRI’s )
• Milnacipran (Savella®) – approved for
fibromyalgia
• No studies for CRPS
• A trial of Milnacipran may be considered
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Autoimmunity
• CRPS is an autoimmune condition in
certain cases
• Auto-antibodies (IgG) against the
autonomic nervous system and peripheral
nerves have been shown
• A small and not well designed trial showed
that low dose Intravenous Immunoglobin
(IVIg) may help with the pain of CRPS for
up to 5 weeks only
Goebel A et al, 2010 IVIg treatment of the CRPS: a randomized trial. Ann Intern Med Feb 2; 152(3)
Blaes FK, et al 2004 Autoimmune etiology of CRPS. Neurology 63:1734-1736
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Spinal Cord Stimulator (SCS)
1
• An electrode is inserted surgically into the
epidural space and connected to an
implanted generator
• The electrode produces an electrical
current is felt as a tingling sensation and
suppresses pain.
• Mechanism of action unknown
• Painful and expensive
Kemler MA, Barendse GA, Kleef M van, Vet HC de, Rijks CP, Furnee CA, et al. Spinal cord stimulation in patients with chronic reflex
sympathetic dystrophy. N Engl J Med 2000;343(9):618-24.
Bennett DS, Alo KM, Oakley J, Feler CA. Spinal cord stimulation for complex regional pain syndrome I (RSD): a retrospective multicenter
experience from 1995 to 1998 of 101 patients. Neuromodulation 1999;2:202-10.
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Spinal Cord Stimulator (SCS)
2
• 25% to 50% of patients develop complications
requiring further surgery.
• Done in a very select group of patients,
improves quality of life but not function
• In a huge study SCS reduced pain and
improved quality of life but did not improve
function for up to 2 years after implantation.
• From 3 years after implantation there was no
difference between those who had it implanted
and those who did not
Kemler MA, Barendse GA, Kleef M van, Wildenberg FA van den, Weber WE. Electrical spinal cord stimulation in reflex
sympathetic dystrophy: retrospective analysis of 23 patients. J Neurosurg
1999;90(1 suppl):79-83.
Calvillo O, Racz G, Didie J, Smith K. Neuroaugmentation in the treatment of complex regional pain syndrome of the
upper extremity. Acta Orthop Belg 1998;64(1):57-63.
Kemler MA, Vet HC de, Barendse GA, Wildenberg FA van den, Kleef M van. The effect of spinal cord stimulation in
patients with chronic reflex sympathetic dystrophy: two years’ follow-up of the randomized
controlled trial. Ann Neurol 2004;55(1):13-8.
98
Topicals
• No significant value, unless used in very early
stages.
• DMSO 45% to 50% with other agents helpful
• Compounded agents such as TCA,
gabapentin, ketamine have been used. No
studies in CRPS.
• Skin lesions of CRPS - topical ketamine
helpful
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NSAID's
• Ibuprofen, naproxen etc
• No real value in CRPS
• Useful if there is co-existing nociceptive
pain.
• Topical NSAID’s may do a better job
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Salves, Lotions and creams
• Not very helpful for the pain of CRPS
• Remember, the cause of the pain is now in
the central nervous cells and not in the
nerves in the arms or legs
• May be helpful for associated joint pains
• Ketamine cream helpful CRPS skin lesions
• Active Max® or DMSO
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The problem is with the glia cells
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Gluten free diet
•Gluten is a protein found in wheat, rye, barley and
other grains
•One can develop an intolerance at any age.
•Gluten as a protein can cause an inflammatory
response in the body.
•Migraines, chronic body ache, abdominal pain,
Fibromyalgia, hypermobility syndromes (EDS),
multiple joint pains
•Hold off on gluten foods for 8 weeks to see if it makes
a difference.
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Exercise and Physical
Therapy
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Effect of RSD on function
• Pain decreases mobility of the limbs. They
experience extreme pain with the slightest
activity
• Not using the limb causes the muscles to
atrophy and the joints to become stiff
• Immobilizing a limb increases RSD pain
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Physical Therapy - Goals
1
• Restore function
• Learn how to properly adjust limb
movements
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Physical Therapy - two types
2
• Pain Focused: Patients who have recently
developed RSD – PT should focus more
on pain
• Time based: Patients who have had RSD
for a while (Chronic) – PT should be more
time based
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Eggs, peanuts and soybean
PEA
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PEA
• Palmitoylethanolamide (PEA) or Palmidrol
• Endogenous lipid
• Very good studies to show its usefulness in
managing neuropathic pain
• No studies done for RSD / CRPS
• Marketed as Normast®, Pelvilen® and
PeaPure ®
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Prof. Rita Levi-Montalcini
• Nobel Prize winner,
1993
• Discovered the
mechanism of action
of PEA
• Pointed out the
relevance of PEA for
medicine
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PEA – Numbers Needed to Treat
• NNT – used to test how effective a
medicine is
• The number of patients need to be treated
for one to benefit compared with a control
• Lower the number, the more effective the
drug is
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NNT for pain drugs
Accessed 24 September 2013: http://palmitoylethanolamide4pain.com/about-2/
112
PEA
2
• Helps with hyperalgesia (severe pain with mildly
painful stimulus) and allodynia (pain to touch)
• Mechanism unclear
• Possible action on Cannabinoid receptor2 (CB2),
Vanilloid receptor (VR1 or TRPV1)
• Anti-inflammatory
• Prevents mast cell activation (mast cells are
important part of inflammation)
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PEA – dose and side effects
• Available as 400mg pills
• Dose: 400mg three times a day
• Best use: open the capsule, pour the powder
on a spoon and put it under the tongue.
• May be done for first 10 days and then pills or
continue as powder for refractory pain
• Start low, go slow.
• Trial of 8 weeks
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Neurotropin®
1
• Non-protein extract from rabbits
• Exact mechanism not known
• Widely used in Japan to treat Neuropathic
pain
• 24 Clinical studies conducted in Japan found
an approximately 40% to 50% response
• Helps with allodynia (pain to touch) and
hyperalgesia
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Service Dogs
• Trained to each person’s
physical impairments
• help with functioning and
independence
• Constant companion, will often
sense its owners pain and will
comfort them both physically and
emotionally
• Can sense distress and call for help
• Service dogs give patients a feeling
of security allowing them to be more
active physically and socially
• Provide stability while walking, open
and close doors, switch on andPradeep
off Chopra, MD
lights
116
Needle stick trauma
• Avoid needle stick injuries as far as possible –
combine a blood test from different physicians
into one procedure
• Ask that the thinnest needle possible be used.
• Let them know that the veins are ‘difficult’.
CRPS patients have thin and friable veins
• For those undergoing regular infusions (IV fluid
rehydration or IV Ketamine) should consider a
chest port
• PICC line is not a good option
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Complications of CRPS
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Complications of CRPS
1
• Can affect any organ
• Poor processing on working memory,
language, executive function
• Lethargy, tiredness, weakness
• Syncope – dizziness and fainting
• Postural Orthostatic Tachycardia Syndrome
(POTS) or Dysautonomia
• Chest wall pain
• Edema – neurogenic or inflammatory
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Complications of CRPS
2
• Muscles – weakness (70%), atrophy,
dystonia, spasms
• Bone and joint pain – very common, bone
loss leading to fractures,
• Low serum cortisol levels (impaired
hypothalamo-pituitary-adrenal function –
low production of cortisol by the body).
Maybe due to opioids
• Low thyroid function (hypothyroid)
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Complications of CRPS
3
• Increased sweating (30%)
• Unexplained spontaneous bruising May not be in an
area that has been traumatized
• Bladder (25%) – frequency, urgency, urinary
incontinence
• Gastrointestinal (41%) – Nausea, vomiting,
intermittent diarrhea, Irritable bowel syndrome,
dysphagia
• Gastroparesis – major issue in CRPS for more than
5 years. Slowing down of the intestines. Fullness
with a little food, bloating. Opioids make it worse
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Mast Cell Activation Disorder
MCAD
Mastocytosis
122
Mast cells
• Found in blood.
• Release histamine (chemical causes the
redness, itchiness in allergy)
• Mast cells release histamine in
inflammation
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Mast Cell Activation Syndrome (MCAD)
•
•
•
•
•
•
•
•
Common in CRPS
Affects most symptoms
Chronic fatigue,
feeling cold (common), feeling hot
Sweats – unexplained
Weight gain
Itchy – comes and goes,
Rash – unpredictable, unprovoked,
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Mast Cell Activation Syndrome (MCAD)
• Sores, poor wound healing,
• Eyes – gritty, increased water, difficulty
focusing
• Mouth – burning mouth
• Dizziness, palpitations, Pre-syncope
(‘almost dizzy’)
• Stomach – intestinal pain
• Bladder pain
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Mast Cell Activation Syndrome (MCAD)
• Inflammatory chemicals released by mast
cells cause nerves to become inflamed.
• Tingling, numbness
• Tics, tremors,
• Brain fog
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Mast Cell Activation Syndrome (MCAD)
• Repeat examination and history by
physician.
• Testing done during flare ups
• Serum tryptase level
• Bone marrow biopsy
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Treatment of MCAD
• Antihistamine ( cold medicines), with
• Zantac®
• Cromolyn Sodium
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Dizziness, racing heart
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Dysautonomia / POTS
• POTS (Postural Orthostatic Tachycardia
Syndrome) or Dysautonomia
• Dizziness, fainting spells, heart palpitations
• Patients have difficulty maintaining their
blood pressure and heart rate with
changes in position
• See a Cardiologist or Neurologist
• May confirm with a Tilt Table Test or
orthostatics
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Dizziness and Palpitations
• Increase in heart rate by 30 beats/ min or
increase to 120 beats/ minute
• Increase salt intake, fluids, compression
stockings
• Medications – beta blockers, midodrine etc
• www.dysautonomiainternational.org
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Weight gain in CRPS
• Medicines that can increase weight: some
antidepressants, gabapentin, pregabalin
(Lyrica®)
• Increase weight from decreased activity
secondary to pain
• Medicines that decrease weight:
milnacipran (Savella®)
• Swelling from edema
• Gluten free diet
• Aqua therapy, daily walk
Sleep in CRPS
• Patients with CRPS often have Nonrestorative sleep
• Active ‘flight and fight’ mechanism
• Overactive sympathetic nervous system
• Sleep home EEG monitor
• Beta blockers (propranolol, metoprolol)
• Buproprion (Wellbutin®), Desmopressin
Skin Lesions in CRPS
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Skin Lesions in RSD
1
• Often go undiagnosed. Little information on skin
lesions
• Different types of skin lesions.
• Swelling and repeated episodes of cellulitis
• Bullae or raised skin lesions filled with fluid
• Early phase of CRPS – mottled red and sweaty
• Later phase of CRPS – smooth, cool, dry and
thin
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Skin lesions in CRPS
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Skin Lesion CRPS – Before
2
Skin Lesion CRPS - After
Skin Lesion CRPS – Before
4
Skin Lesion CRPS – After
Nerve entrapment
• Often seen after a cast is put on
• Maybe either right away or after some time
with chronic pressure over the nerve
• Peroneal neuralgia
• Thoracic Outlet syndrome
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CRPS in children
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Children and RSD
1
• Children develop the same symptoms
• 58% to 93% of cases of RSD in children will
resolve with proper treatment
• Relapses following apparent healing are often
observed (10% to 48%)
• More common in girls
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Children and RSD 2
• It is often labeled as a behavioral disorder, conversion
disorder and parents are labeled as having
Munchausen’s syndrome
• To make any of the above diagnosis is very challenging.
• Usually takes years by a Psychologist in conjunction with
other treating physicians.
• Imperative that all other medical conditions have been
ruled out
• Cannot be made by physicians with little or no mental
health training.
• Very important that parents pay close attention to the
child’s complaints
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Children and RSD
4
• Often associated with other conditions
such as
– Ehler’s Danlos Syndrome (EDS)
– Mitochondrial disorder
– Nerve entrapment (Thoracic outlet syndrome
etc)
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Ehlers Danlos Syndrome
• Defect in tissue (connective tissue) that
provides support to many body parts
• Extremely loose joints (Double jointed)
• Dislocate or subluxate joints easily
• Hyperelastic skin that bruises easily
• Inherited
• Symptoms of CRPS may be either because
of repetitive trauma or nerve damage
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Ehlers Danlos Syndrome
1
• EDS is a group of inherited disorders
• Affects connective tissue (‘connects’)
• Connective tissue is found in skin, joints and blood
vessels
• Very flexible, unstable joints (‘Double jointed’),
stretchy skin and many other symptoms
• Orthostatic intolerance / POTS - excessive distention
of veins in upright posture
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Mitochondrial Disease
• Mitochondria are tiny parts found in cells of the
human body
• They produce 90% of the energy for the body
• Mitochondrial disease is genetic disorder where
the mitochondria fail to produce enough energy
• Nerve cells require a tremendous amount of
energy to function and these patients may
present with symptoms of CRPS, or
• if they develop CRPS then its important to treat
the mitochondrial disease first.
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Amputation
• No evidence that amputation for pain only
makes a positive contribution to the
treatment of CRPS
• It may be life saving in case of severe
infection with the threat of sepsis or if there
is cancer
Dielissen PW, Claassen AT, Veldman PH, Goris RJ. Amputation for reflex sympathetic dystrophy. J Bone Joint Surg Br
1995;77(2):270-3
Stam HJ, Rijst H van der. The results of amputation in reflex sympathetic dystrophy of the upper extremity – an analysis of 7 cases.
.
PMR 1994;4:134-6
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RSDS.ORG – research library
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Information on RSD
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Stories of hope
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Acknowledgements
• Jim Broatch,
Executive Vice President and Director,
RSDSA
• Board Members of RSDSA
• Juliana Renee Hill
• Nova Southeastern University
• www.painsupplements.us
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Thank you
Pradeep Chopra, MD, MHCM
painri@yahoo.com
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