Download - Imaging Pain: From Research to Clinical Application M. CATHERINE BUSHNELL MCGILL UNIVERSITY
Imaging Pain: From Research to Clinical Application
M. CATHERINE BUSHNELLMCGILL UNIVERSITY
Brain imaging allows us to measure
neural basis of pain perception
Important technique for examining neural changes related to chronic pain
Brain imaging techniques used to study pain mechanisms
MRI: provides functional and anatomical information
PET: provides neurochemical information
Evoked Potentials: provides temporal information
ACC: Anterior cingulate cortex; IC: Insular
cortex. Apkarian A, et al. Eur J Pain.
2005;9:463–485.
S1 S2
ACC IC
Imaging reveals sensory and limbic regions activated by pain
Pain affect without “pain sensation” in patient with postcentral lesion
Sensory and limbic regions have different roles in pain processing
Ploner et al. 1999
Imaging shows that the pain network activated by many types of
pain
Frida Kahlo
Chronic pain can be associated with changes in pain processing.
Post-herpetic neuralgia
Diabetic neuropathy
Back pain
In chronic pain patients the pain network can be activated by tactile stimuli
(allodynia)
Tactile allodynia related to neuropathic pain reflected in the brain
Hofbauer RK, et al. Clin J Pain. 2006;22:104–108.
DMN = Default mode network.Cauda F. PLoS ONE. 2009;4:e4542.
Control DMN Patient DMN
DMN Patient-Control
Chronic pain can alter brain resting state activity
diabetic neuropathic pain
Hypersensitivity in “functional” pain syndromes
Pukall et al 2005
Vulvar vestibulitis
Increased stimulus-evoked brain activation to light touch in vulvar
vestibulitis
Pukall CF, et al. Pain. 2005;115:118–127.
Hypersensitivity in fibromyalgia
Wood et al, Eur. J. Pain 2007
Increased activation to pressure in fibromyalgia
Gracely et al 2002
Pain intensity = 0/10
Pain intensity = 10/10
Measuring ongoing chronic pain in MRI
scanner
MRI: Magnetic resonance imaging. Baliki MN, et al. J Neurosci. 2006;21:12165–12173.
Baliki MN, et al. J Neurosci. 2006;21:12165–12173.
Chronic back pain has transient and sustained
components
Baliki MN, et al. J Neurosci. 2006;21:12165–12173.
Correlates of increasing pain are similar to acute pain processing
Correlates of high sustained pain involve emotional and cognitive regions
Chronic back pain activates two brain circuits
Imaging shows that some cortical regions are involved in descending pain modulation
Descending modulation of pain
Information from cortex ultimately received in spinal cord
Schweinhardt and Bushnell, J. Clin. Investigation, in press
Psychological factors modulate pain via these descending modulatory pathways
Emotions Attention
Attention to pain
Distraction from pain
Bushnell et al. 1999
Attention Modulates Pain
Emotions alters pain
Mood alters pain-evoked activity in limbic brain regions
Villemure & Bushnell 2009
Bad mood + Pain Good mood + Pain
Anterior cingulate cortex
Attention and emotion activate different modulatory circuitry in brain
Villemure & Schweinhart 2010
Attentional focussing and/or negative emotional states can
contribute to chronic pain states
Strigo I et al, Arch Gen Psychiatry 65: 1275-1284, 2008.
Major depressive disorder associated with altered descending inhibition
during pain
Imaging has revealed that chronic pain patients have changes in brain grey matter that might reflect changes in pain modulation
Tracey and Bushnell J. Pain 2008 (review)
Gray matter decreased first shown by Apkarian in back pain patients
Apkarian AV, et al. J Neurosci. 2004;24:10410–10415.
Similar findings with multiple chronic pain conditions
Gray matter decreases in chronic tension-type
headache
Schmidt-Wilcke T, et al. Neurology. 2005;66:1483–1486.
Gray matter decreases in fibromyalgia
Kuchinad A, et al. J Neurosci. 2007;404:1104–1107.
Davis KD, et al. Neurology. 2008;70:153‒154. Epub 2007 Oct 24.
Decreased cortical thickness in IBS patients
Gray matter decreases in regions related to pain modulation may lead to
increased pain
M1
S1
Adapted from Price DD. Science. 2000;288:1769–1772.
IS THERE A RELATIONSHIP BETWEEN CHANGES IN GRAY MATTER AND PERCEPTUAL AND/OR
BEHAVIORAL MEASURES?
Correlations with behavior
Neuropathic painGray matter changes in trigeminal neuropathic pain correlated with allodynia
Borsook et al PloS One 3:e3396, 2008
Disruption of working memory correlates with frontal cortex thinning in fibromyalgia
ACT score
Cor
tica
l thi
ckne
ss
Ceko et al 2010
Life-style related differences in cortical thickness
Villemure, Cotton, Čeko & Bushnell, IASP 2010
Long-term yoga practitioners have increased pain tolerance and increased gray matter
Are gray matter changes cause or effect?
Longitudinal studies
Correlation with pain duration in cross-sectional studies
Back pain patientsBack pain patients Fibromyalgia patientsFibromyalgia patients
Gray matter reduction related to duration of symptoms
Apkarian AV, et al. J Neurosci. 2004;24:10410–10415. Kuchinad A, et al. J Neurosci. 2007;404:1104–1107.
DAVID A. SEMINOWICZ, TIMOTHY H. WIDEMAN, LINA NASO, ZEINAB HATAMI-KHOROUSHAHI,
SUMMAYA FALLATAH, MARK WARE, PETER JARZEM, YORAM SHIR,
JEAN A. OUELLET, M. CATHERINE BUSHNELL, AND LAURA S. STONE
Treating Chronic Low Back Pain Reverses Structural Brain Changes
Longitudinal Studies
Cortical thinning in back pain reversed by treatment
pre-treatment post-treatment
Seminowicz et al 2010
Thicker DLPFC post-treatment
Seminowicz et al 2010
Less pain thicker DLPFC
Seminowicz et al 2010
Rodent imaging longitudinal studies
EPM: Elevated plus-maze; MRI: Magnetic resonance imaging; SNI: Spared nerve injury.Seminowicz DA, et al., Neuroimage, 2009.
Neuropathic rats followed for five months
Anxiety increases later than hyperalgesia
Seminowicz DA, et al., Neuroimage, 2009.
von Frey test
Log
(50%
von
Fre
y th
resh
old
(g))
Time post-surgery (weeks)
Sham
SNI
Mechanical hyperalgesia
Elevated plus maze
Num
ber
of
exits
fro
m
clos
ed a
rms
Sham SNI
Time post-surgery (weeks)
**
Anxiety behavior
Reduced PFC thickness in SNI rat
Seminowicz DA, et al., Neuroimage 2009.
Mea
n re
lativ
e vo
xel s
ize
Time post-surgery (weeks)
Sham
SNI*
*
PET imaging shows that some chronic pain patients have
disruptions offorebrain neurotransmitter systems
Tracey and Bushnell J. Pain 2008 (review)
Fibromyalgia patients have
reduced µ-opioid binding potential in pain-
related brain regions
NACC
AMYG
dACC
AMYG = Amygdala; dACC = Dorsal anterior cingulate; NACC = Nucleus accumbens.Harris RE, et al. J Neurosci. 2007;27:1000–1006.
35-
25-
15-
5-
5-
-15-
-25-
-35-Post GP
Left
Post Put Left
Post CN Left
V Striatum
Ant GP Left
Ant CN LeftC
han
ge i
n B
ind
ing
Pote
nti
al
(%)
Adapted from: Wood PB, et al. Eur J Neurosci. 2007;25:3576–3582.
Ant=Anterior; CN=Caudate nucleus; GP=Globus pallidus; Post=Posterior; Put: Putamen.
Fibromyalgia patients have reduced basal ganglia dopamine release in response to
muscle pain
Healthy controls Fibromyalgia patients
*p<0.001
*
**
***
Brain imaging has revealed:
Distinct neural signature for pain that includes sensory and limbic regions of the brain
Chronic patients can have altered pain transmission and modulation
Chronic pain involves more emotional and cognitive processing than does acute pain
Long-term pain can alter brain anatomy and chemistry and associated emotions and cognitive function