Transcript Slide - St. Joseph's Health Care London

Manfred Harth MD FRCPC
Professor Emeritus U.W.O
Potential Conflicts of Interest
Honoraria from :
Solvay
Jansen-Ortho
Pfizer,
Bristol-Myers Squibb
Boehringer Ingelheim
Review board for a Fralex trial
Grant support from Eli Lilly.
IMEs for several legal firms ,insurance
companies,and WSIAT.
Betty M., a 50 year old woman, has developed
pain in her neck, shoulders, elbows, forearms,
low back, thighs, knees, ankles and feet over the
past year.
She has fatigue, and a non-refreshing sleep.
We therefore immediately suspect that Betty has :
a) Polymyalgia Rheumatica
b) Rheumatoid Arthritis
c) Fibromyalgia
d) Galloping hypochondriasis
Fibromyalgia (Fibromyalgia Syndrome)
is a condition characterized by chronic
pain, fatigue, and a non-refreshing sleep.
So, she has
Fibromyalgia ?
Prove it !
ACR Classification Criteria
At least 3 regions of chronic
pain (> 3 months) :
1 above the waist ;
1 below the waist ;
1 on each side of the body ;
1 in the centre of the body.
+ > 11/18 tender points
Betty M has 16 TPs
Betty M has Fibromyalgia
FM occurs in all ethnic groups,
all over the world.
Its prevalence is 2-4%
About 85% of patients are women
The highest prevalence is between
40-60 years of age.
Associated Disorders
Chronic Fatigue Syndrome
Migraine
Irritable bowel syndrome
Irritable bladder
Restless leg syndrome
Anxiety state
Depression
Associated Diseases
Endometriosis
RA
SLE
AIDS
Lyme Disease
Hepatitis C
Where is the Problem ?
Central Nervous
System Sensitization



Refers to hyperexcitablility of
certain spinal cord nerve cells
Characterized by  spontaneous
activity, enlarged receptive fields
and increased response to sensory
input
Pain related to central
sensitization does not follow the
normal pattern of “nerve
territories” (dermatomal
distribution)
Cerebral
Cortex
Sensory
Nerve (First
Order)
Thalamus
Nociceptors
hyperexcitable
Second
Order
Nerve
Spinal
Cord
Normal
Sensitized
Central Sensitization
(cont’d)
Allodynia = pain
due
to a
 Is
relevant
to FM because it is
stimulus that doesn’t
oftennormally
associated with extensive
provoke pain
secondary hyperalgesia and
allodynia
Several studies (e.g., Staud et al.,
2002; 2003) suggest abnormalities in
spinal cord processes in FM

Quantitative Sensory Testing uses the
nociceptive flexion reflex R-III (NFR)
• Stimulate Sural nerve
(pain pathway)
• Measure latency of
biceps femoris response

Median NFR:
• FMS patients median threshold =
22.7 mA (range 17.5-31.7)
• Normal controls median threshold
= 33 mA (range 28.1-41.0)
• FMS vs NC : p<0.001

Suggest hyperexcitability of
spinal cord pain mechanisms in
FMS (allodynia)
Brain Imaging
Research in FM
fMRI response to painful heat
Normal Control
Fibromyalgia
DB Cook et al J Rheumatol 2004; 31:364-78
Normal Control
Fibromyalgia
Deficient in FM
Normal controls show activation of rostral anterior
cingulate cortex (A), and pulvinar nucleus of
thalamus (B) during painful stimulation.
K B Jensen et al Pain 2009;144:95-100;
Adapted from I J Russell et al Arthritis Rheum 1994;37:1593-1601
Nerve growth factor in CSF
45
40
35
30
25
20
Controls
FMS
15
10
5
0
Adapted from SL Giovengo et al J Rheumatol 1999;26:1564-9
24 hour growth hormone (GH) levels
A Leal-Cerro et al J Clin Endocrinol Metab 1999; 84:3378-81
Effects of IL-6 on NE blood levels
FMS
Normal controls
DJ Torpy et al Arthritis Rheum 2000; 43: 872-80
Brain activity and sleep in FMS
Half the patients with FMS have
phasic alpha sleep (compared to 7% of controls).
All of these have a non-refreshing sleep.*
* S Roizenblatt et al Arthritis and Rheum 2001; 44:222-30
Serotonin, Dopamine, GABA, Glutamate etc…
Betty does not want to use medications
at this stage.
" What else can I do other than take
drugs ??? "
ENERGY, PAIN RELIEF,WORK CAPACITY
L Brosseau, Wells GA, Tugwell P et al. Physical
Thrapy 2008; 88: 857-71
Pain, Disability, Depression
Brosseau L et al. Ottawa Panel evidence-based clinical
practice guidelines for strengthening exercises in the
management Phys Ther. 2008 Jul;88(7):873-86
Exercise
• Includes aerobic exercise, flexibility
and strength training
• No consensus about what
type,duration or intensity are best
Cognitive behavioural therapy ( CBT )
Kati Thieme,Dennis Turk,Herta Flor
Arthritis Care Res 2007;57:830-6
3 FM groups (40-43)
CBT, OBT, Attention placebo (AP)
CBT:focus on patient thinking,
problem solving, relaxation.
Operant-behavioural therapy : focus
on pain behaviour rather than on
thought.
15 weekly sessions of 2 hrs each
p<0.001
% ge with clinically significant
reduction or increase in pain
at 12 months
p<0.005
% ge with clinically significant
reduction or increase in
physical impairment at 12
months
Betty improves somewhat, but still
complains of pain and fatigue.
She is ready now to accept the use of
medications
"What choices have I got ? "
μ opioid receptor
agonist
Has GABAergic,
serotonergic and
noradrenergic effects
Tramadol
Acts on opioid receptors in brain
Inhibits serotonin and norepinephrine
reuptake,therefore interferes with pain
transmission in spinal cord
Available in Canada as Tramadol slow
release, or with acetaminophen (Tramacet)
Tramadol and Acetaminophen
Effect on pain
80
70
60
Pain
50
score
40
in
mm
30
Baseline
At 90 days
20
p < 0.001<
10
0
T+A
Placebo
RM Bennett et al Am J Med 2003;114:537-45
AMITRIPTYLINE
CYCLOBENZAPRINE
& FRIENDS
Placebo
Cyclobenzaprine
Cycl
Amitriptyline
Placebo
Ami
S Carette et al Arthritis Rheum 1994; 37:32-40
Gabapentin and Pregabalin
BLOCK
Blockage of α2δ subunit in Ca channel. Reduced release
of glutamate,serotonin,noradrenalin,dopamine,
substance P.
Pregabalin 13 weeks
P
A
I
N
PJ Mease et al J Rheumatol 2008; 35:502-14
Patient global impression of change-PGIC
Dropouts 33-41%
FIQ improved in 1 trial
Pregabalin: Adverse Effects
Dizziness
Somnolence
Headaches
Weight gain
Edema
Duloxetine over 6 months
Improvement in pain
Duloxetine -Patient Global Improvement
I J Russell et al Pain 2008;136:432-44
50-55% of patients dropped out
over 6 months
Adverse effects : nausea,dry
mouth, constipation,insomnia
Other treatments
•Electroacupuncture
•Gabapentin
•Pramipexole
•Nabilone
•Milnacipran ( not available in Canada)
•Raloxifen
•Sodium oxybate
•Fluoxetine (large doses)
No evidence for efficacy
NSAIDs
Narcotics
All antidepressants not mentioned above
Tender point injections
Powered and controlled by
team of health care professionals
Drugs
Aerobic
Education
exercise
Srengthening
exercise
CBT