neuromodulation: the autonomic nervous system and

NEUROMODULATION THE AUTONOMIC NERVOUS SYSTEM AND GASTROINTESTINALTRACT DISORDERS

TERRY L. POWLEY, PH.D.

PURDUE UNIVERSITY

• MULTIPLE REFRACTORY GI DISORDERS EXIST.

• VISCERAL ATLASES OF THE GI TRACT ARE AVAILABLE.

• REMEDIATION WITH ELECTROMODULATION MAY BE PRACTICAL.

TERRY l. POWLEY, PH.D. NEUROMODUlATION: THE AUTONOMIC NERVOUS SYSTEM AND GASTP.OINTESTINAL TRACT DISORDERS

PURDUE UNIVERSITY

INTERNATIONALNEUROMODULATION SOCIETY

12TH WORLD CONGRESS

50 "'I: 0 40·-IS-I:• 30"' !

A.-0 20..•..a E 10::::t z

TERRY l. POWLEY, PH.D. NEUROMODUlATION: THE AUTONOMIC NERVOUS SYSTEM AND GASTP.OINTESTINAL TRACT DISORDERS

PURDUE UNIVERSITY

DISORDERS TO TREAT WITH NEUROMODULATION

I

' I

Gastrointestinal Tract

ACHALASIA DYSPHAGIA GERD MEGA ESOPHAGUS

==..:.= --- "" .:.= --- .. _ _ ,

COLITIS IBS CROHN'S DISEASE HIRSCHSPRUNG DISEASE CHAGAS DISUSE

GASTROPARESIS GUT DYSMOTILITY DYSPEPSIA VISCERAL PAIN NAUSEA, EMESIS

,, l1 '

,,OBESITY PYLORIC STENOSIS DUMPING REFLUX I:'

. - -·-- -

Awodesk@ Ma;·a@

TERRY l. POWLEY, PH.D. PURDUE NEUROMODUlATION: THE AUTONOMIC NERVOUS SYSTEM AND GASTP.OINTESTINAL TRACT DISORDERS UNIVERSITY

11

TIME The Obesity Epidemic in America

·.

TERRY l. POWLEY, PH.D. PURDUE NEU ROMODUlATION : THE AUTO N OMIC NERVOUS SYSTEM A N D G A STP.OINTESTINAL TRACT DISORDERS UNI V E R SI TY

ROUX-EN-Y BYPASS

-----

Bypassed portion of stomach

Gastric -"'~pouch

Bypassed - Jejunum duodenum

-1" food

____,,.,. digestivejuice

TERRY l. POWLEY, PH.D. PURDUE NEU ROMODUlATION: THE AUTONOMIC NERVOUS SYSTEM A N D GASTP.OINTESTINAL TRACT DISORDERS UNIVERSITY

8y~s~

portion of i t()(l\3Ch

•

TERRYl. POWLEY, PH.D. PURDUE UHIVlflSITYNEUROMOOUlATION: THE AUTONOMIC NERVOUS SYSTEM ANO 0.-STP.OINTESTINAL TRACT DISORDERS

• DESPERATE PATIENTS

• ABSENCE OF SATISFACTORY PHARMACOLOGICAL TREATMENTS

• POPULAR MEDIA HYPE

• ABSENCE OF A SOLID MECHANISTIC UNDERSTANDING

• UNCRITICAL ACCEPTANCE OF PROPONENT'S CLAIMS

• MYOPIA REGARDING SIDE EFFECTS


ENTERIC NERVOUS SYSTEM:

''LIRLE BRAIN'' IN GUT

Tjaden & Trainor

~~ • •

COMPLEXITY MADE

SIMPLE

----~~~~-/ --~--~---

The VAGUS may be the answer!!

COMPLEXITY MADE

SIMPLE

Leblanc, 2001


Prech~ and Powley

TERRY L. POWLEY, PH.D. PURDUE NEUROMODULATION : THE A UTO NOMIC NERVOUS SYSTEM A ND GASH OINTESTINAL TRACT DISORDERS UNIVERSITY

I J

"'

Wang & Pawley, 2007

TERRY l. POWLEY, PH.D. PURDUE NEU ROMODUlATION : THE AUTO N OMIC NERVOUS SYSTEM A N D G A STP.OINTESTINAL TRACT DISORDERS UNI VER SI TY

Wang & Pawley, 2000

TERRYl. POWLEY, PH.D. PURDUE U HIV l flSITYNEUROMOOUlATION: THE AUTONOMIC NERVOUS SYSTEM ANO 0.-STP.OINTESTINAL TRACT DISORDERS

ROUX-EN-Y BYPASS


Bypassed Jejunum duodenum

--~,,. food

.._ • digestive juice

VAGAL NETWORK

TERRY l. POWLEY, PH.D. PURDUE NEU ROMODUlATION : THE AUTO N OMIC NERVOUS SYSTEM A N D GASTP.OINTESTINAL TRACT DISORDERS UNIVERSITY

ROUX-EN-Y BYPASS

INCISION


Bypassed Jejunum duodenum

--~,,. food

.._ • digestive juice

VAGAL NETWORK

TERRY l. POWLEY, PH.D. PURDUE NEU ROMODUlATION : THE AUTO N OMIC NERVOUS SYSTEM A N D GASTP.OINTESTINAL TRACT DISORDERS UNIVERSITY

VAGAL MOTOR INNERVATION

OF MYENTERIC

PLEXUS

TERRY L. POWLEY, PH.D. PURDUE NEUROMODUl.ATION: THE AUTONOMIC NERVOUS SYSTEM AND GASTP.OINTESTINAl TRACT DISORDERS UNIVlftSJTY

VAGAL & SYMPATHETIC MOTOR · MYENTERIC PLEXUS

..


PERCENT MYENTERIC GANGLIA INNERVATED BY VAGUS

100

7.' 80

60

40

20

0

to-'~~... 6

GASTR'C _.::\''l\I All "°'"'"" ~~ I ~ /

11·1, '\ J...........i.

I\\ \ I ~ HEPATIC -1 ~ \ \\. L)7~'"Y" ..........J I / \\..,·······............. ..

brarich I \ \, • " ,.. 6................ . I :;- ·

J \ \. l "·..·r "' I CELIAC · \ \ brariches

! I.\ .. ........~~-V \,._::::·~---t4<===~-·=,,.....'""-::.:¢-;::-.:i!::::~-- -···-~~

....

)( .;If) ~ ll) (I) 0 0 0 0 ::E ~ (')

N '<t g (I) 'O c:~ :::> 0 0 0 0 .., .., .., .., ~ & " .. :::>i5 Q. a: ::::> .. .8 ~ ~ 'O

"'4> .... z a: .... w :::> z ...J ~ IL 8 < DUODENUM JEJUNUM - CECUM COLON a:

Berthoud, Corlson, and Powley

TERRY l. POWLEY, PH.D. PURDUE NEU ROMODUlATION: THE AUTONOMIC NERVOUS SYSTEM AND GASTP.OINTESTINAL TRACT DISORDERS UNIVERSITY

VAGALSENSORY INNERVATION:

INTRAGANGLIONIC LAMINAR

ENDING (IGLE) ~ .. 100

VAGAL SENSORY • IGLEs • PLATES ON MYENTERIC GANGLIA


VAGAL SENSORY IGLE INNERVATES CHOLINERGIC NEURONS & IGNORES NITRERGIC NEURONS IN MYENTERIC GANGLION

-

...

A

J

i

l/,

j

r

0

E

F

VAGAL SENSORY INNERVATION:

INTRAMUSCULAR ARRAY (IMA)

F

VAGALSENSORY IMAs:

STRETCH RECEPTORS?

MUSCLE SPINDLE ORGAN ANALOGUES?

AXON REFLEXES?

---

~ 1 ·

.,,

I I

I

B\ ~

l ~

SMf I I SM

ICC •

DA

IMAs ARE REGIONALLYSPECIALIZED AND CONCENTRATED:

SPHINCTERS, FORESTOMACH, nc.

20000

15000 ..0

B.10000

l 5000

0

A: Receptive Field Size

*

Pyloric IMA5 Antral IMAs

B: Length of Arbors

4000 .. 3000

[ 2000

1000

0 Pyloric IMAs Antral IMAs

C: Width of Arbor

800

600

§. 400

200

0 Pyloric IMAt An tral IMA$

D: Depth of Arbor

40

30

~ 20

10

0 Pyloric IMAs Antral IMAs

OBESITY: VBLOC THERAPY

CONTROLLER

NEUROREGULATOR

ELECTRODES

Sarr et al., 2012 TRANSMIT COIL

Fit:, 1. Elt:< ·1rocl<~ i11 1pL111 i.:cl 011 auu:rior and po:.h:1i:u 1,,;a~1l tnu1k.s (01ig-i11~, 1 1 11 ~'g11i llt: .1tio11 . X·I).

Camilleri et al., 2008

TERRY l. POWLEY, PH.D. PURDUE NEU ROMODUlATION: THE AUTONOMIC NERVOUS SYSTEM A N D GASTP.OINTESTINAL TRACT DISORDERS UNIVERSITY

VAGAL MOTOR INNERVATION:

ESOPHAGUS

Powley et al., 2013

ENTERIC NERVOUS SYSTEM: 11LITILE BRAIN'' IN GI TRACT

A B

Myenteric plexus

I Deep muscular plexus

Muscularis Mucosa! plexus Mucosa ~'---- Deep muscular mucosae ~'1).'V plexus

Submucous plexus

Mucosa plexus

Furness & Costa

TERRY L. POWLEY, PH.0. PURDUE NEUROMODULATION : THE A UTO NOMIC NERVOUS SYSTEM A ND GASHOINTESTINAL TRACT DISORDERS UNIVERSITY

--

VAGALSENSORY AXONS INNERVATE

GI MUCOSAL Villi WITH

CHEMORECEPTORS

A

D ' \ t

c c c

'

Powley et al., 2011

VAGALSENSORY AXONS ALSO INNERVATE

CRYPTS

A

SM SbMuc .,

Crypts !

I I

• MULTIPLE REFRACTORY GI DISORDERS EXIST.

• VISCERAL ATLASES OF THE GI TRACT ARE AVAILABLE.

• REMEDIATION WITH ELECTROMODULATION MAY BE PRACTICAL.


GI NEUROMODULATION PRIORITIES

• HIGH-PRIORITY OPPORTUNITIES:

o OBESITY

o GASTROPARESIS

• TECHNOLOGICAL NEEDS:

o NEXT-GENERATION STIMULATORS

• Fiber-caliber tuned

• Closed Loop

• Self-programming, real time

o DATA ON VAGAL INTEGRATIVE ARCHITECTURE


MACROPHAGES INTERACT WITH:

MYENTERIC GANGLIA (AND EXTRINSIC NERVE AXONS)

Phillip$ &Powley, 2012

A

MACROPHAGES INTERACT WITH:

MYENTERIC GANGLIA (AND EXTRINSIC NERVE AXONS)

c

Phillips & Powley, 2012

SYMPATHETIC GANGLION (CELIAC) EXPOSED FOR SURGERY

Phillips et a l.

SYMPATHETIC MOTOR AXONS CO-INNERVATE

SMOOTH MUSCLE AND

MYENTERIC GANGLIA

B

D A,8

C,E

Walter, 2014

GASTRIC BYPASS

• DESPERATE PATIENTS

• ABSENCE OF SATISFACTORY PHARMACOLOGICAL TREATMENTS

• POPULAR MEDIA HYPE

• ABSENCE OF A SOLID MECHANISTIC UNDERSTANDING

• UNCRITICAL ACCEPTANCE OF PROPONENT'S CLAIMS

• MYOPIA REGARDING SIDE EFFECTS

TERRY L POWLEY, PH.D. PURDUE UNIVEASITYNEVROMODUIATION: THE AUTONOMIC NERVOUS SYSTEM AND GASTtolNTESTlNAt TRACT DISORDERS

ENTERIC NERVOUS SYSTEM: ''LITILE BRAIN'' IN GI TRACT

LONGITUDINAL MUSCLE MOTOR NEURON CIRCULAR MUSCLE

INTERNEURON MOTOR NEURON

ORAL ANAL

INTERNEURON NETWORK OF IPANs

Furness, 2006

TERRY L. POWLEY, PH.D. PURDUE NEUROMODULATION : THE A UTO NOMIC NERVOUS SYSTEM A ND GASH OINTESTINAL TRACT DISORDERS UNIVERSITY

VAGAL MOTOR · MYENTERIC PLEXUS

' .. -'

\

I I

B

'

,


GASTROPARESIS: GASTRIC STIMULATION

Fig. 2 Depiction of laparoscopic gastric electrical stimulation placement \\~th lrocar placement and intraopemtive endoscopy •

• •

5mm Smm

Smm

CCF ~ 2012~

TERRY l. POWLEY, PH.D. PURDUE NEU ROMO DUlATION : THE AUTO N OMIC NERVO US SYSTEM A N D G A STP.OINTESTINAL TRACT DISORDERS UNI V ERSI TY

VAGAL MOTOR INNERVATION OF

ESOPHAGUS:

CO-INNERVATION OF MUSCLE FIBERS

AND GANGLIA

Powley et al., 2013

neuromodulation: the autonomic nervous system and

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