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Developing Models For New Treatment Technologies
Bringing Precision to the Pain Field
Alex DaSilva, DDS, DMedScDirector, Headache & Orofacial Pain Effort (H.O.P.E.)
Co-Director, fNIRS Laboratory, Center for Human Growth & Development (CHGD)
Founder, Michigan Clinical Augmented Reality for Pain unit (M-CARP unit)
Biologic & Materials Sciences Department, University of Michigan School of Dentistry
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Disclosure: MoxyTech LLC (Co-Founder)
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TMD
MIG
FIBRO
TNP
TNP!
MIG!
FIBRO!
DEN!
TMD!
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• 116 Million
Americans With
Chronic Pain
• Costs $635 billion a
year
• Costs per patient
additional $4.5-7.7
thousand in health
care expenditures
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VAS 5.9 6.3 5.7
PainTrekP.A.I.N.S.
3.5% 3.6% 25.7%
PainTrekAverage
1.4 2.0 2.1
PainTrekPain Area
7.3% 5.5% 36.4%
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What are the Targets in our
Brains for Pain Relief?
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Optic radiationsNeuroplasticity in Migraine
Syste
mC
lin
icN
eu
roim
ag
e
Limbic
Cognition
Mood
ACC
Prescot et al, 2009
Visual
Aura
Hadjikhani et al, 2001
Visual
Aura
MT/V5
DaSilva et al, 2006
Inhibitory
Allodynia
PAG
DaSilva et al, 2007
Sensorimotor
Headache
SI/MI
DaSilva et al, 2007
Sensorimotor
Headache
Thal
DaSilva et al, 2007
Syste
mC
lin
icN
eu
roim
ag
e
Limbic
Cognition
Mood
ACC
Prescot et al, 2009
Visual
Aura
Hadjikhani et al, 2001
Visual
Aura
MT/V5
DaSilva et al, 2006
Inhibitory
Allodynia
PAG
DaSilva et al, 2007
Sensorimotor
Headache
SI/MI
DaSilva et al, 2007
Sensorimotor
Headache
Thal
DaSilva et al, 2007
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3D-Immersive NeuroNavigation in Migraine
DaSilva et al, 2014
H.O.P.E. Lab, University of Michigan
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eSpontaneous Migraine Attacks
Mu-Opioid Activation during Allodynia
DaSilva et al, 2014
Nascimento et al, 2014
H.O.P.E. Lab, University of Michigan
Migraine Allodynia
10
14
18
Midbrain
μ-Opioid Activation
NIH-NINDS K23 NS062946
NIH-NINDS R01 NS094413
DANA Foundation’s Brain Award
Migraine Research Foundation
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Pain Sensitivity
HC-vmhnm HC-w
Voxel_BP_hippo TMD and Genetic Group
OJJ
- lnfuo;ionVolumlil --------------------------------
250 ------i-------i-----+-----+-------l--------------~----------------1__.____ h ____ -----+-----t--------f-------i----
'" ~fMf#~~~~-~iltE.~~~-~~fA~1~.
. 0
HC-vrMnm HC-w
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So what?
Can you do something to
help me?
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Nguyen et al, PAIN, Volume 82, Issue 3, 1999, 245 - 251
INVASIVE Motor Cortex Stimulation In The Treatment Of Chronic Pain.
Face
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Donnell et al, 2015
H.O.P.E. Lab, University of Michigan
Non-Invasive H.O.P.E. lab M1 HD-tDCS Montage for Chronic Pain.
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VAS 50% Responders from Week 1 to Week 6
Group Active Sham Total
<50% VAS decrease 3 8 11
≥50% VAS decrease 9 4 13
Total 12 12 24
Chi-Square X2=4.1958 p=0.04
Donnell et al, 2015
H.O.P.E. Lab, University of Michigan
TMD: MONTH FOLLOW-UP
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Donnell et al, 2015
H.O.P.E. Lab, University of Michigan
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Donnell et al, 2015
H.O.P.E. Lab, University of Michigan
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tDCS and Chronic Migraine
Population
There were no significant differences between sham and active tDCS group
Neuromodulation
+
Molecular Neuroimage
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μ-Opioid Activation During tDCSS
ha
m
DosSantos et al, 2014
H.O.P.E. Lab, University of Michigan
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μ-Opioid Activation During tDCSS
ha
m
Ac
tive
DosSantos et al, 2014
H.O.P.E. Lab, University of Michigan
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μ-Opioid Activation During tDCSS
ha
mA
cti
ve
DosSantos et al, 2014
H.O.P.E. Lab, University of Michigan
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What is the Chronic Effect
of Sham and Active
Neuromodulation?
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Thalamus ACC Anterior Insula
GA
BA
(A
IU)
Glutamate ê GABA é
Foerster et al, 2015
H.O.P.E. Lab, University of Michigan
MICHR Clinical Trial Planning
CTSA High-Tech funding: UL1RR024986
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Q. ;;; u £ 0 £.. "' .c <.>
. ;;
Pre-Treament Glx within the Anterior Cingulate Predicts Subsequent Clinical Response to Sham and Active tDCS
4
! Q.
r=-0.81:. 2 •:! Sham tDCS p<0.001 Q.
"' ~ 0 • •£..
·2
.. • li .e
.e +-~~~~~~~~~~~~~~~
8 9 10 11 12 13
.e+-~~~~~~~~~~~~~~~
8 9 10 11 12
Baseline ACC Glx (AIU)
•
2
8. "' ~ 0 c•Q... ·2
£ u
0 .. £....:ii .e .c <.>
Baseline ACC Glx (AIU)
• r=-0.87
Active tDCS p<0.001
•
•
• •
Foerster et al, 2015H.O.P.E. Lab, University of Michigan
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So what?
I can not read my patient’s
brain in the office!
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So what?
Clinical Neuroimaging
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Cooling Stimulus(Averaged)
Lower SI cortex
Upper SI cortex
Dental Pain Evoked Response at SI
** ***
Racek et al, 2015
H.O.P.E. Lab, University of MichiganColgate-Palmolive
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Cooling Stimulus(Averaged)
Cooling Stimulus(Averaged)
Dental Pain Evoked Response at Left Prefrontal Cortex
Dental Pain Evoked Response at Right Prefrontal Cortex
Racek et al, 2015
H.O.P.E. Lab, University of Michigan
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Hu et al
Under Review
H.O.P.E. Lab, University of Michigan
Stronger PFC-S1Functional Connectivity 11
Stronger Activity in PFC During Pain Expectation 12
Faster and Stronger Cold-Related Activity in S1 13
Stronger Pain-Related Activity in S1 14
HIGHER CLINICAL PAIN
Functional Connectivity
Functional Correlation
Stronger PFC-S1Functional Connectivity 11
Stronger Activity in PFC During Pain Expectation 12
Faster and Stronger Cold-Related Activity in S1 13
Stronger Pain-Related Activity in S1 14
HIGHER CLINICAL PAIN
Functional Connectivity
Functional Correlation
Stronger PFC-S1Functional Connectivity 11
Stronger Activity in PFC During Pain Expectation 12
Faster and Stronger Cold-Related Activity in S1 13
Stronger Pain-Related Activity in S1 14
HIGHER CLINICAL PAIN
Functional Connectivity
Functional Correlation
Stronger PFC-S1Functional Connectivity 11
Stronger Activity in PFC During Pain Expectation 12
Faster and Stronger Cold-Related Activity in S1 13
Stronger Pain-Related Activity in S1 14
HIGHER CLINICAL PAIN
Functional Connectivity
Functional Correlation
Stronger PFC-S1Functional Connectivity 11
Stronger Activity in PFC During Pain Expectation 12
Faster and Stronger Cold-Related Activity in S1 13
Stronger Pain-Related Activity in S1 14
HIGHER CLINICAL PAIN
Functional Connectivity
Functional Correlation
Stronger PFC-S1Functional Connectivity 11
Stronger Activity in PFC During Pain Expectation 12
Faster and Stronger Cold-Related Activity in S1 13
Stronger Pain-Related Activity in S1 14
HIGHER CLINICAL PAIN
Functional Connectivity
Functional Correlation
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Time
Pattern Recognition + Clinical Augmented Reality Neuroimaging (fNIRS)
…
Region 1
Region 2
Region 3
Region 4
Region 5
Region 6
Oxy-Hb & Deoxy-Hb
Training trials Testing trials
Accuracy: 80% (Block wide)
Predictor
Predictor 1
K-NN
Painful
Non-
Painful
70%
Predictor 2
K-NN & DT-
Augmented Reality
-
+
Brain Stimulation
+
K-NN: K Nearest Neighborhood DT: Decision Tree