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. PURDUE NEUROMODUlATION: THE AUTONOMIC NERVOUS SYSTEM AND GASTP.OINTESTINAL TRACT DISORDERS UNIVERSITY 50 INTERNATIONAL I:"' NEUROMODULATION SOCIETY 0 40 ·­IS 12TH WORLD CONGRESS -I: -• 30 !"' A. -..0 20 ..a• E 10 z::::t TERRY l. POWLEY, PH.D. PURDUE NEUROMODUlATION: THE AUTONOMIC NERVOUS SYSTEM AND GASTP.OINTESTINAL TRACT DISORDERS UNIVERSITY DISORDERS TO TREAT WITH NEUROMODULATION ACHALASIA DYSPHAGIA GASTROPARESIS GERD GUT DYSMOTILITY MEGA ESOPHAGUS DYSPEPSIA ,, VISCERAL PAIN l1 ' I NAUSEA, EMESIS OBESITY ,, ' 11 I PYLORIC STENOSIS ==..:.= --- "" .:.= --- .. _ _, DUMPING REFLUX COLITIS I:' . - IBS -·-- - CROHN'S DISEASE HIRSCHSPRUNG DISEASE CHAGAS DISUSE Gastrointestinal Tract Awodesk@ Ma;·a@ TERRY l. POWLEY, PH.D. PURDUE NEUROMODUlATION: THE AUTONOMIC NERVOUS SYSTEM AND GASTP.OINTESTINAL TRACT DISORDERS UNIVERSITY 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~ portionof i t()(l\3Ch • TERRYl. POWLEY, PH.D. PURDUE NEUROMOOUlATION: THE AUTONOMIC NERVOUS SYSTEM ANO 0.-STP.OINTESTINAL TRACT DISORDERS UHIVlflSITY • 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 NEUROMODUlATION: THE AUTONOMIC NERVOUS SYSTEM AND GASTP.OINTESTINAL TRACT DISORDERS UNIVERSITY ENTERIC NERVOUS SYSTEM: ''LIRLE BRAIN'' IN GUT Tjaden & Trainor ~~• • COMPLEXITY MADE SIMPLE ----~~~~- / --~--~---­ The VAGUS may be the answer!! COMPLEXITY MADE SIMPLE Leblanc, 2001 TERRY l. POWLEY, PH.D. PURDUE NEUROMODUlATION: THE AUTONOMIC NERVOUS SYSTEM AND GASTP.OINTESTINAL TRACT DISORDERS UNIVERSITY 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 NEUROMOOUlATION: THE AUTONOMIC NERVOUS SYSTEM ANO 0.-STP.OINTESTINAL TRACT DISORDERS U HIV l flSITY ROUX-EN-Y BYPASS VAGAL NETWORK Bypassed portion of stomach Bypassed Jejunum duodenum --~,,. food .._ • digestive juice 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 VAGAL NETWORK INCISION Bypassed portion of stomach Bypassed Jejunum duodenum --~,,. food .._ • digestive juice 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 .. TERRY l. POWLEY, PH.D. PURDUE NEUROMODUlATION: THE AUTONOMIC NERVOUS SYSTEM AND GASTP.OINTESTINAL TRACT DISORDERS UNIVERSITY PERCENT MYENTERIC GANGLIA INNERVATED BY VAGUS 100 to-'~~... 6 7. ' 80 GASTR'C _.::\''l\I All "°'"'"" ~~ I ~ / 11·1, '\ J...........i. 60 I\\ \ I ~ 40 HEPATIC -1 \ \\. .......... '"Y" ..........J brarich I ~\ \, • " L,.. )7~ 6................I / \..\..,··· ····... I :;- · 20 J \ \. l "·..·r "' I CELIAC .... · \ \ brariches ! I.\ 0 .. ........~~-V \ ,._::::·~---t4<===~-·=,,.....'""-::.:¢-;::-.:i!::::~-- -···-~~ )( .; If) ~ (') ll) (I) 0 0 0 0 ::E :::> ~ N '<t g (I) 'O c: :::> ~ 0 0 0 0 .., .., .., .., ~ & " 4> Q. ~ ..~ "' i5 a: ::::> .. .8 'O .... 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 ~ 100. ENDING (IGLE) VAGAL SENSORY • IGLEs • PLATES ON MYENTERIC GANGLIA TERRY l. POWLEY, PH.D. PURDUE NEUROMODUlATION: THE AUTONOMIC NERVOUS SYSTEM AND GASTP.OINTESTINAL TRACT DISORDERS UNIVERSITY VAGAL SENSORY IGLE INNERVATES CHOLINERGIC NEURONS & IGNORES NITRERGIC NEURONS IN MYENTERIC GANGLION - ... A /,l J j i r VAGAL SENSORY INNERVATION: INTRAMUSCULAR ARRAY (IMA) F 0 E F VAGALSENSORY IMAs: 1~· .,, STRETCH RECEPTORS? I I I MUSCLE SPINDLE B ORGAN ANALOGUES? \ ~ AXON REFLEXES? ~ SM l f I SM I ICC • A--- D A: Receptive Field Size B: Length ofArbors 20000 4000 . * 15000 3000 ..0 B.10000 [ 2000 l 5000 1000 0 0 Pyloric IMA5 Antral IMAs Pyloric IMAs Antral IMAs IMAs ARE REGIONALLY C: Width ofArbor SPECIALIZED AND 800 CONCENTRATED: 600 §. 400 200 SPHINCTERS, 0 FORESTOMACH, nc. Pyloric IMAt An tral IMA$ D: Depth of Arbor 40 30 ~ 20 10 0 Pyloric IMAs Antral IMAs OBESITY: VBLOC THERAPY CONTROLLER NEUROREGULATOR ELECTRODES Fit:, 1. E lt:< · 1ro cl <~ i11 1pL111 i.:cl 011 auu:rior and po:.h:1i:u Sarr et al., 2012 1 TRANSMIT COIL ,,;a~1l tnu1k.s (0 1ig-i11~, 1 1 11 ~'g11 i llt: .1 tio11 . 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 Mucosa Muscularis Mucosa! plexus mucosae ~'---- Deep muscular ~'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 A VAGALSENSORY AXONS INNERVATE GI MUCOSAL Villi WITH CHEMORECEPTORS D '\ t c c c -- ' Powley et al., 2011 A VAGALSENSORY ., AXONS ALSO SM SbMuc Crypts ! INNERVATE CRYPTS I I • MULTIPLE REFRACTORY GI DISORDERS EXIST. • VISCERAL ATLASES OF THE GI TRACT ARE AVAILABLE. • REMEDIATION WITH ELECTROMODULATION MAY BE PRACTICAL. TERRY l. POWLEY, PH.D. PURDUE NEUROMODUlATION: THE AUTONOMIC NERVOUS SYSTEM AND GASTP.OINTESTINAL TRACT DISORDERS UNIVERSITY 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 TERRY l. POWLEY, PH.D. PURDUE NEUROMODUlATION: THE AUTONOMIC NERVOUS SYSTEM AND GASTP.OINTESTINAL TRACT DISORDERS UNIVERSITY MACROPHAGES INTERACT WITH: MYENTERIC GANGLIA (AND EXTRINSIC NERVE AXONS) Phillip$ &Powley, 2012 A MACROPHAGES INTERACT WITH: MYENTERIC GANGLIA c (AND EXTRINSIC NERVE AXONS) Phillips & Powley, 2012 SYMPATHETIC GANGLION (CELIAC) EXPOSED FOR SURGERY Phillips et a l. D A,8 B SYMPATHETIC MOTOR AXONS C,E CO-INNERVATE SMOOTH MUSCLE AND MYENTERIC GANGLIA Walter, 2014 • DESPERATE PATIENTS • ABSENCE OF SATISFACTORY PHARMACOLOGICAL TREATMENTS GASTRIC BYPASS • 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 NEVROMODUIATION: THE AUTONOMIC NERVOUS SYSTEM AND GASTtolNTESTlNAt TRACT DISORDERS UNIVEASITY 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 B ' .. ' - \ ' I , I TERRY l. POWLEY, PH.D. PURDUE NEUROMODUlATION: THE AUTONOMIC NERVOUS SYSTEM AND GASTP.OINTESTINAL TRACT DISORDERS UNIVERSITY 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 .