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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
Disclosure: MoxyTech LLC (Co-Founder)
TMD
MIG
FIBRO
TNP
TNP!
MIG!
FIBRO!
DEN!
TMD!
• 116 Million
Americans With
Chronic Pain
• Costs $635 billion a
year
• Costs per patient
additional $4.5-7.7
thousand in health
care expenditures
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%
EHR Collaboration
What are the Targets in our
Brains for Pain Relief?
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
3D-Immersive NeuroNavigation in Migraine
DaSilva et al, 2014
H.O.P.E. Lab, University of Michigan
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
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
So what?
Can you do something to
help me?
Neuromodulation
Nguyen et al, PAIN, Volume 82, Issue 3, 1999, 245 - 251
INVASIVE Motor Cortex Stimulation In The Treatment Of Chronic Pain.
Face
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.
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
Donnell et al, 2015
H.O.P.E. Lab, University of Michigan
Donnell et al, 2015
H.O.P.E. Lab, University of Michigan
tDCS and Chronic Migraine
Population
There were no significant differences between sham and active tDCS group
Neuromodulation
+
Molecular Neuroimage
μ-Opioid Activation During tDCSS
ha
m
DosSantos et al, 2014
H.O.P.E. Lab, University of Michigan
μ-Opioid Activation During tDCSS
ha
m
Ac
tive
DosSantos et al, 2014
H.O.P.E. Lab, University of Michigan
μ-Opioid Activation During tDCSS
ha
mA
cti
ve
DosSantos et al, 2014
H.O.P.E. Lab, University of Michigan
What is the Chronic Effect
of Sham and Active
Neuromodulation?
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
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
So what?
I can not read my patient’s
brain in the office!
So what?
Clinical Neuroimaging
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
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
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
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
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