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15-0800-Foreman-SCS #428AE6 INTERNATIONAL NEUROMODULATION SOCIETY 9TH WORLD CONGRESS SPINAL CORD MECHANISMS— VISCERAL: THE C1/C2 CONNECTION Robert D. Foreman University of Oklahoma Health Sciences Center Department of Physiology Oklahoma City, Oklahoma USA 11-15 SEPTEMBER 2009 SEOUL, SOUTH KOREA SF Hobbs, Uhtaek Oh, TJ Professor Emeritus Brennan, MJ Chandler, Hanyang University Kee Soon Kim, and RD College of Medicine Foreman. Urinary bladder and hindlimb stimuli inhibit Department of Physiology T1-T6 spinal and spino- Seoul reticular cells. Am. J. Physiol. 258: R10-R20, 1990 Uhtaek Oh, Ph.D. 1987 University of Oklahoma Health Sciences Center Department of Physiology SPINAL CORD MECHANISMS— VISCERAL: THE C1/C2 CONNECTION • Introduction—Why C1/C2 • C1/C2 Spinothalamic Tract Cells, Vagus and the Heart • C1/C2 Propriospinal Modulation of Nociceptive Cardiac Input • C1/C2 SCS Modulation of Nociceptive Cardiac Input • C1/C2 SCS Modulation of Colonic Input • C1/C2 SCS Augmentation of Cerebral Blood Flow • Summary HEART PAIN CAN RADIATE TO THE JAW, TEETH, AND NECK UPPER CERVICAL SPINAL CORD STIMULATION (SCS) UNSTABLE ANGINA PECTORIS IN HUMANS Stimulation Parameters: intensity<paresthesias, ~200us, ~50Hz NEURAL MECHANISMS UNDERLYING ANGINA PECTORIS TO THE NECK & JAW Thalamus CL What is the explanation for VPLc CM-Pf VPM neck and jaw pain of VPMpc VPI angina pectoris??? NTS Early Clinical Observations—by Lindgren & Olivecrona, 1947 and Medulla White & Bland, 1948 effects of bilateral sympathectomy C1/C2 • “migration of pain” particularly to the neck, jaws, and temples C5/C6 • pain appears on exertion • disappears after nitroglycerin C7/C8 • pain relieved by injecting mandibular nerve with procaine Foreman T1-T5 • most likely pathway-vagus Ann. Rev. Physiol.61, 1999 SPINAL CORD MECHANISMS— VISCERAL: THE C1/C2 CONNECTION • Introduction—Why C1/C2 • C1/C2 Spinothalamic Tract Cells, Vagus and the Heart • C1/C2 Propriospinal Modulation of Nociceptive Cardiac Input • C1/C2 SCS Modulation of Nociceptive Cardiac Input • C1/C2 SCS Modulation of Colonic Input • C1/C2 SCS Augmentation of Cerebral Blood Flow • Summary NEURAL MECHANISMS UNDERLYING ANGINA PECTORIS Does Cardiac Input Excite C1/C2 STT Cells Via the Vagus? Thalamus CL VPLc CM-Pf VPM VPMpcVPI ??? NTS Medulla Vagus C1/C2 C5/C6 C7/C8 Foreman Ann. Rev. Physiol.61, 1999 T1-T5 VAGAL INNERVATION OF THE C1/C2 SPINAL CORD Nucleus < Tractus Solitarius < < C1/C2 EFFECTS OF VAGAL STIMULATION ON ACTIVITY OF STT CELLS AT DIFFERENT SPINAL SEGMENTS Intact Ipsilateral Vagus Vagotomy 40 Thalamus CL VPLc 20 CM-Pf NTS Rate (imp/s) 0 Medulla IC Saline Algesic Algesic Heart Chemicals Chemicals C1/C2 Heart Heart C5/C6 C7/C8 T1-T5 Foreman Ann. Rev. Physiol.61, 1999 NEURAL MECHANISMS UNDERLYING ANGINA PECTORIS Cardiac Input Excites C1/C2 STT Cells Via the Vagus Thalamus CL VPLc CM-Pf VPM VPMpcVPI NTS Medulla Vagus C1/C2 C5/C6 C7/C8 Foreman Ann. Rev. Physiol.61, 1999 T1-T5 SPINAL CORD MECHANISMS— VISCERAL: THE C1/C2 CONNECTION • Introduction—Why C1/C2 • C1/C2 Spinothalamic Tract Cells, Vagus and the Heart • C1/C2 Propriospinal Modulation of Nociceptive Cardiac Input • C1/C2 SCS Modulation of Nociceptive Cardiac Input • C1/C2 SCS Modulation of Colonic Input • C1/C2 SCS Augmentation of Cerebral Blood Flow • Summary DO NEURAL NETWORKS OF C1/C2 SEGMENTS MODULATE NOXIOUS CARDIAC INPUT? C1/C2 ?? T3/T4 Spinal integration Cardiac afferents EXPERIMENTAL SETUP RECORDINGS FROM T3/T4 SPINAL NEURONS CHEMICAL STIMULATION OF C1/C2 Spike 3 Data acquisition and Oscilloscope & analysis Audio amplifier Microelectrode A B C A, Glutamate (activates cell bodies but not axons) pledget on C1/C2 segments; B, cell recording at T3/T4 segments; C, pericardial sac EFFECTS OF C1/C2 GLUTAMATE ON T3 SPINAL NEURON RESPONSES INTRAPERICARDIAL BRADYKININ BEFORE ROSTRAL C1 TRANSECTION SpontaneousSpontaneous Activity Activity (imp/s) (imp/s) TotalTotal Response Response (imp) (imp) DurationDuration of of Response Response (s) (s) 1414 18001800 160160 1600 140 1212 1600 140 14001400 10 120120 10 1200 1200 100 8 100 8 10001000 s 80 s 80 imps 800 imps imps/s 6 800 imps/s 6 6060 600600 44 40 400400 40 2 20 2 200200 20 00 00 00 Before Glutamate After Glutamate 60 MINUTES AFTER ROSTRAL C1 TRANSECTION SpontaneousSpontaneous Activity Activity (imp/s) (imp/s) TotalTotal Response Response (imp) (imp) DurationDuration of of Response Response (s) (s) 2000 1616 2000 200200 18001800 180 1414 180 16001600 160160 1212 14001400 140140 10 10 12001200 120120 1000 s 100 88 1000 s 100 imps imps imps/s imps/s 800 80 66 800 80 600 6060 4 600 4 40 400400 40 2 20 2 200200 20 0 00 00 0 Qin et al. Auton Neurosci 114: 11-116, 2004 NEURAL HIERARCHY ORIGINATES FROM C1-C2 SEGMENTS Glutamate effects are preserved after rostral C1 spinal transections C1/C2 ! C1/C2 Propriospinal Pathway T3/T4 Cardiac afferents ! Excitation Inhibition SPINAL CORD MECHANISMS— VISCERAL: THE C1/C2 CONNECTION • Introduction—Why C1/C2 • C1/C2 Spinothalamic Tract Cells, Vagus and the Heart • C1/C2 Propriospinal Modulation of Nociceptive Cardiac Input • C1/C2 SCS Modulation of Nociceptive Cardiac Input • C1/C2 SCS Modulation of Colonic Input • C1/C2 SCS Augmentation of Cerebral Blood Flow • Summary NEURAL HIERARCHY ORIGINATING FROM C1/C2 SEGMENTS Does C1/C2 SCS Modulate Cardiac Input onto Spinal Neurons? Spinal Cord Stimulation C1/C2 ! 90%MT, 200 us, 50 Hz ? T3/T4 Cardiac afferents ! Excitation Inhibition Spinal cord EXPERIMENTAL SETUP Spike 3 Data acquisition and Oscilloscope & analysis Audio amplifier Stimulator Microelectrode A C1/C2 T1/T2 B A, Cell recording at T3/T4 segments; B, Pericardial Sac Qin et al., Neurosci Res. 2007 May;58(1):58-66. EFFECT OF C1/C2 SCS ON T3 NEURONAL RESPONSES TO BRADYKININ A Control C1/C2 SCS on Recovery 20s 31 Keyboard 31 Keyboard 31 Keyboard 40 40 40 30 30 30 Rate Histogra Histogra Histogra Events Events Events 20 5 20 5 20 5 10 10 10 (imp/s) 0 0 0 0 5.0 5.0 5.0 2.5 2.5 2.5 volt volt volt 4 rawtrace 0.0 4 rawtrace 0.0 4 rawtrace 0.0 -2.5 -2.5 -2.5 -5.0 IB -5.0 IB -5.0 IB 100 100 100 0 0 0 mmHg mmHg mmHg 2 UBD 2 UBD 2 UBD -100 -100 -100 -200 -200 -200 5.0 5.0 5.0 2.5 2.5 2.5 pedal pedal pedal 1 volt 0.0 1 volt 0.0 1 volt 0.0 -2.5 -2.5 -2.5 -5.0 -5.0 -5.0 B 220 240 260 280 300 320 340 360 380 400 420 440 460 480 500 520 540 560 580 600 1380 1400 1420 1440 1460 1480 1500 1520 1540 1560 1580 1600 1620 1640 1660 1680 1700 1720 1740 1760 2300 2320 2340 2360 2380 2400 2420 2440 2460 2480 2500 2520 2540 2560 2580 2600 2620 2640 2660 2680 Control s C8/T1 SCS on s Recovery s 20s 31 Keyboard 31 Keyboard 60 31 Keyboard 60 60 60 Rate 40 40 40 untitled 9 Events Histogra Events untitled 9 Events 5 20 20 20 (imp/s) 0 0 5.0 0 0 5.0 5.0 2.5 2.5 2.5 volt 4 rawtrace 0.0 rawtrace volt volt 4 rawtrace 0.0 4 0.0 -2.5 -2.5 -2.5 -5.0 IB IB -5.0 IB -5.0 200 200 200 mmHg 3 BP BP mmHg mmHg 3 BP 3 0 0 0 5.0 5.0 5.0 2.5 2.5 2.5 volt 1 pedal 0.0 volt pedal volt 1 pedal 0.0 1 0.0 -2.5 -2.5 -2.5 -5.0 -5.0 -5.0 960 980 1000 1020 1040 1060 1080 1100 1120 1140 1160 1180 1200 110 120 130 140 150 160 170 180 190 200 210 220 230 240 250 260 270 280 290 300 310 320 330 340 350 80 100 120 140 160 180 200 220 240 260 280 300 320 s IB – Intrapericardials Bradykinin—Algogenic Chemical s Qin et al., Neurosci Res. 2007 May;58(1):58-66. NEURAL HIERARCHY ORGINATING FROM C1/C2 SEGMENTS Spinal Cord Stimulation C1/C2 ! 90%MT, 200 us, 50 Hz SCS depends the dorsal columns but not the propriospinal pathway T3/T4 Cardiac afferents ! Excitation Inhibition Spinal cord SPINAL CORD MECHANISMS— VISCERAL: THE C1/C2 CONNECTION • Introduction—Why C1/C2 • C1/C2 Spinothalamic Tract Cells, Vagus and the Heart • C1/C2 Propriospinal Modulation of Nociceptive Cardiac Input • C1/C2 SCS Modulation of Nociceptive Cardiac Input • C1/C2 SCS Modulation of Colonic Input • C1/C2 SCS Augmentation of Cerebral Blood Flow • Summary NEURAL HIERARCHY ORIGINATING FROM C1/C2 SEGMENTS: DOES C1/C2 SCS MODULATE L6-S2 NEURONAL RESPONSES TO COLONIC DISTENSION? Spinal Cord Stimulation C1/C2 ! 90%MT, 200 us, 50 Hz L6-S2 Spinal cord ! Excitation Inhibition EXPERIMENTAL SETUP Oscilloscope Pen Discriminator writer Stimulator Microelectrode A B C2 L2 C A, SCS on C1/C2 or L1/L2 segments; B, cell recording at L6-S2 segments; C, colorectal distention NEURAL HIERARCHY ORIGINATING FROM C1/C2 SEGMENTS Spinal Cord Stimulation C1/C2 ! 90%MT, 200 us, 50 Hz S1 Spinal Neuron Responses to SCS 31 Keyboard 31 Keyboard 31 Keyboard 31 Keyboard 20 20 20 20 20 15 Rate15 15 15 histogram Events histogram histogram Events Events Events 5 10 5 histogram 10 10 5 10 5 10 5 (imp/s)5 5 5 0 0 0 0 10 10 0 10 10 5 5 5 5 raw cell volts raw cell raw cell volts volts volts 4 4 raw cell CRD 60 4 60 4 60 60 0 0 0 0 (mmHg) -5 -5 -5 -5 5.0 5.0 5.0 5.0 2.5 2.5 2.5 SCS on C1-C2 2.5 emg volts emg emg volts volts volts 3 0.0 3 emg 0.0 3 0.0 3 0.0 -2.5 -2.5 -2.5 -2.5 -5.0 -5.0 -5.0 -5.0 300 300 300 300 200 200 200 200 torr bp bp bp torr torr bp 2 100 2 torr 100 2 100 2 100 0 0 0 0 -100 -100 -100 -100 5.0 5.0 5.0 5.0 2.5 2.5 2.5 2.5 marker volts marker marker volts volts marker 1 0.0 1 volts 0.0 1 0.0 1 0.0 -2.5 -2.5 -2.5 -2.5 -5.0 -5.0 -5.0 -5.0 1380 1400 14201660 14401680 14601700 14801720 15001740 15201760 15401780 15601800 15801820218016001840220016201860222016401880224016601900226016801920228017001940230017201960232021801740198023402200200023602220202023802240204024002260 24202280 24402300 24602320 24802340 25002360 25202380 25402400 25602420 2440 2460 2480 2500 2520 2540 2560 L6-S2 s s s s Spinal cord ! Excitation Inhibition NEURAL HIERARCHY ORIGININATING FROM L5-S2 SEGMENTS S1 Spinal Neuron Responses to SCS 31 Keyboard 31
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