Transcript Document

Fibromyalgia:
A Chronic Widespread
Neurologic Pain Condition
Disease Overview, Diagnosis, and Management
PBP00542 © 2009 Pfizer Inc. All rights reserved. Printed in USA/September 2009
1
What is Fibromyalgia?
Pathogenesis of Fibromyalgia
Clinical Features and Diagnosis of Fibromyalgia
Management of Fibromyalgia
2
The Normal Pain Processing Pathway
3. A signal is sent via
the ascending tract
to the brain, and
perceived as pain
Pain
Perceived
4. The descending tract carries
modulating impulses
back to the
dorsal horn
2. Impulses from afferents
depolarize dorsal horn
neurons, then, extracellular
Ca2+ diffuse into neurons
causing the release of Pain
Associated Neurotransmitters
• Glutamate
• Substance P
1. Stimulus sensed by
the peripheral nerve
(ie, skin)
1Staud
R and Rodriguez ME. Nat Clin Pract Rheumatol. 2006;2:90-98.
2Gottschalk A and Smith DS. Am Fam Physician. 2001;63:1979-1984.
Presynaptic
neuron
Postsynaptic
neuron
Glutamate
Substance P
3
Central Sensitization: A Theory for
Neurological Pain Amplification in FM
•
Central sensitization is believed to be an underlying cause of the
amplified pain perception that results from dysfunction in the CNS1
– May explain hallmark features of generalized heightened
pain sensitivity2
• Hyperalgesia – Amplified response to painful stimuli
• Allodynia – Pain resulting from normal stimuli
•
•
fMRI data demonstrated that low-intensity stimuli in patients with
FM produce pain comparable to high-intensity stimuli in controls3
Theory of central sensitization is supported by
– Increased levels of pain neurotransmitters4,5
• Glutamate
• Substance P
fMRI = functional magnetic resonance imaging
1Staud
R and Rodriguez ME. Nat Clin Pract Rheumatol. 2006;2:90-98.
DA and Clauw DJ. J Pain. 2009;10(8):777-791.
3Gracely RH, et al. Arthritis Rheum. 2002;46:1333-1343.
4Sarchielli P, et al. J Pain. 2007;8:737-745.
5Vaerøy H, et al. Pain. 1988;32:21-26.
2Williams
4
Central Sensitization Produces
Abnormal Pain Signaling
Perceived pain
Ascending
input
Normal Pain Processing
Descending
modulation
Pain
stimuli
Nociceptive afferent fiber
Perceived pain
(hyperalgesia/allodynia)
Pain Processing in FM
• Increased release of pain neurotransmitters
glutamate and substance P
Induction of central sensitization leading
to abnormal pain processing
Pain
amplification
Minimal
stimuli
1Adapted
2Woolf
from Gottschalk A and Smith DS. Am Fam Physician. 2001;63:1979-1984.
CJ. Ann Intern Med. 2004;140:441-451.
5
FM: An Amplified Pain Response
Subjective Pain Intensity
10
Pain in FM
8
Hyperalgesia
6
(when a pinprick causes an
intense stabbing sensation)
4
Allodynia
Pain
amplification
response
Normal Pain
Response
(hugs that feel painful)
2
0
Stimulus Intensity
Adapted from Gottschalk A and Smith DS. Am Fam Physician. 2001;63:1979-1986.
6
fMRI Study Supports the Amplification of
Normal Pain Response in Patients with FM
Patients with FM Experienced High
Pain with Low Grade Stimuli
14
Pain Intensity
12
10
8
6
4
Red: Activation at low intensity stimulus
in patients with FM
2
0
1.5
2.5
3.5
Stimulus Intensity (kg/cm2)
FM (n=16)
Subjective pain control
Stimulus pressure control
4.5
(n=16)
fMRI = functional magnetic resonance imaging
Gracely RH, et al. Arthritis Rheum. 2002;46:1333-1343.
Green: Activated only at high intensity
stimulus in controls
Yellow: Area of overlap (i.e., area activated
at high intensity stimuli in control patients
was activated by low intensity stimuli in
patients with FM)
7
Patients With FM Have Elevated Pain
Neurotransmitter Substance P in Their CSF
Substance P concentration
(fmoles/mL)†
In 3 Separate Clinical Studies, Substance P, a Pain
Neurotransmitter, Was Elevated in FM Patients1-3
50
40
p<0.001
42.8
p<0.001
FM Patients
Healthy Control Subjects
43.0
30
p<0.03
20
10
16.3
17.0
19.3
12.8
0
Russell 1994 * 1
Russell 1995* 2
Bradley* 3
FM Patients
n=32
n=24
n=14
Healthy Control Subjects
n=30
n=24
n=10
CSF = cerebrospinal fluid
*CSF sample collected via lumbar puncture in FM and healthy controls and SP levels assessed by radioimmunoassay
†fmoles/mL = femtomole/mL = 10-15 mole/mL
1Russell
IJ, et al. Arthritis Rheum. 1994;37:1593-1601.
IJ, et al. Myopain 1995: Abstracts from the 3rd World Congress on Myofascial Pain and Fibromyalgia; July 30 - August 3, 1995; San Antonio, TX.
3Bradley LA, et al. Arthritis Rheum. 1996;suppl 9:212. Abstract 1109.
2Russell
8
Patients with FM Have Elevated Pain
Neurotransmitter Glutamate in Their CSF
CSF Level of Glutamate (µg/mL)
CSF Levels of Glutamate
2.5
FM Patient (n=20)
Control (n=20)
2.0
p<0.003
1.5
1.0
0.5
0
FM Patient
CSF = cerebrospinal fluid
Sarchielli P, et al. J Pain. 2007;8:737-745.
Control
9
FM Pathophysiology: Summary
•
•
Central sensitization is a leading theory
of FM pathophysiology1
fMRI data supports FM as a disorder of central
pain amplification2
– Areas activated by high intensity stimuli in control patients
were activated by low intensity stimuli in patients with FM
•
Elevated pain neurotransmitters in CSF of patients
with FM3-5
– Several studies showed elevated levels of glutamate
and substance P
– Elevated levels suggest that this may contribute
to pain amplification
CSF = cerebrospinal fluid
fMRI = functional magnetic resonance imaging
1Staud
R and Rodriguez ME. Nat Clin Pract Rheum. 2006;2:90-98.
2Gracely RH, et al. Arthritis Rheum. 2002;46:1333-1343.
3Russell
IJ, et al. Arthritis Rheum. 1994;37:1593-1601.
LA, et al. Arthritis Rheum. 1996;suppl 9:212. Abstract 1109.
5Sarchielli P, et al. J Pain. 2007;8:737-745.
4Bradley
10