Developing Models For New Treatment ... - Pain Consortium · Brains for Pain Relief? Neuroplasticity in Migraine Optic radiations System ... Aura Hadjikhani et al, 2001 Aura MT/V5

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


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


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


TMD: MONTH FOLLOW-UP

Donnell et al, 2015


Donnell et al, 2015


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



ha

m

Ac

tive




ha

mA

cti

ve



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


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



Dental Pain Evoked Response at Left Prefrontal Cortex

Dental Pain Evoked Response at Right Prefrontal Cortex

Racek et al, 2015


Hu et al

Under Review


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

Documents

Developing Models For New Treatment ... - Pain Consortium · Brains for Pain Relief? Neuroplasticity in Migraine Optic radiations System ... Aura Hadjikhani et al, 2001 Aura MT/V5